Podcasts about entresto

In this episode, TRC Healthcare editors, Sara Klockars, PharmD, BCPS, and Stephen Small, PharmD, BCPS, BCPPS, BCCCP, CNSC, discuss notable new meds of 2024. Listen in as our editors discuss several novel drugs approved in 2024...and highlight some medications now available in a new dosage form. They'll review efficacy, safety, and considerations for use with these new treatment options.  None of the speakers have anything to disclose. TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist's Letter, Pharmacy Technician's Letter, or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.Claim CreditThe clinical resources mentioned during the podcast are part of a subscription to Pharmacist's Letter, Pharmacy Technician's Letter, and Prescriber Insights: On Demand Webinar: Notable New Meds of 2024Articles: Clarify the Role of Sofpironium for HyperhidrosisWatch for Ensifentrine for COPDDon't Rush to Aprocitentan for Resistant HypertensionNew Drug for Schizophrenia Targets Muscarinic ReceptorsBe Familiar With Carbidopa/Levodopa OptionsNew Drug Overviews:Aprocitentan (Tryvio)Epinephrine Nasal Spray (Neffy)Send us a textCheck out our NEW podcasts. Rumor vs TruthYour trusted source for facts... where we dissect the evidence behind risky rumors and reveal clinical truths.Clinical CapsulesTRC editors break down the most impactful clinical developments - giving you clear, actionable takeaways in just minutes.If you're not yet a subscriber, find out more about our product offerings at trchealthcare.com. Follow, rate, and review this show in your favorite podcast app. Find the show on YouTube by searching for ‘TRC Healthcare' or clicking here. You can also reach out to provide feedback or make suggestions by emailing us at ContactUs@trchealthcare.com.

This Day in Legal History: Wilder Elected First Black GovernorOn January 13, 1990, Lawrence Douglas Wilder made history by becoming the first African American elected governor of a U.S. state, taking office as the 66th governor of Virginia. Sworn in by former U.S. Supreme Court Justice Lewis F. Powell Jr., Wilder's inauguration symbolized a milestone in American political and civil rights history. His election represented the culmination of decades of progress in dismantling racial barriers, particularly poignant in Virginia, a state with a complex history as the capital of the Confederacy during the Civil War. Wilder, a Democrat, had previously served as the lieutenant governor of Virginia from 1986 to 1990, and earlier in the Virginia State Senate, where he was known for his advocacy for civil rights, education, and criminal justice reform. His gubernatorial campaign focused on pragmatic leadership, fiscal responsibility, and bridging divides in a state still grappling with its historical legacies of segregation and inequality. Wilder's narrow victory highlighted the increasing political influence of African Americans in the U.S. and underscored the potential for diverse representation at the highest levels of government.During his tenure, Wilder prioritized issues such as improving public education, reducing the state budget deficit, and enacting stricter gun control measures. Following his time as governor, he continued to serve the public as the mayor of Richmond from 2005 to 2009, further solidifying his legacy as a trailblazer and dedicated public servant. Wilder's career remains a testament to the possibilities of progress and a reflection of the changing political and social landscape of the United States.The U.S. Supreme Court is considering a case involving a law that requires TikTok's Chinese parent company, ByteDance, to sell the platform or face a U.S. ban, with a compliance deadline of January 19, 2025. TikTok's lawyer, Noel Francisco, warned that endorsing such a law could set a precedent allowing Congress to target other companies on similar grounds, potentially infringing on First Amendment protections. Francisco cited examples like AMC Theaters, which was once owned by a Chinese company, to illustrate the broader implications. The law was passed with bipartisan support due to concerns over national security, with lawmakers fearing the Chinese government could use TikTok to spy on Americans or spread propaganda. TikTok content creators, represented by lawyer Jeffrey Fisher, argued the law unfairly singles out TikTok while ignoring other Chinese-owned platforms like Temu, which also collect U.S. user data. Solicitor General Elizabeth Prelogar, representing the Biden administration, defended the law, stating it is essential to push ByteDance toward divestiture to mitigate risks from foreign adversaries. If implemented, the ban would prevent new downloads of TikTok, leading to the app's eventual obsolescence. The justices appeared divided, balancing national security concerns with constitutional protections of free speech. Former President Donald Trump has urged the court to delay the deadline until his administration, beginning January 20, could pursue a political resolution.TikTok warns of broad consequences if Supreme Court allows ban | ReutersU.S. Special Counsel Jack Smith, who prosecuted federal cases against Donald Trump for attempting to overturn the 2020 election and mishandling classified documents, has resigned from the Department of Justice. His resignation, effective January 10, 2025, follows Trump's victory in the 2024 election, which made the continuation of these cases against the president-elect untenable due to DOJ rules prohibiting the prosecution of a sitting president. Smith's cases were already hindered by legal setbacks, including rulings granting Trump broad immunity for actions taken as president.Smith submitted his final confidential report on January 7 and defended the merits of his prosecutions while requesting dismissal of the charges. His work led to historic firsts, as Trump became the first former U.S. president federally indicted, accused of retaining classified national security documents and attempting to disrupt the certification of the 2020 election. Both cases, however, faced legal delays, with one dismissed by a Trump-appointed judge and the other paused due to Supreme Court rulings on presidential immunity.Trump criticized Smith's investigations as politically motivated and pledged to dismiss him upon taking office. Smith's tenure included significant legal challenges, culminating in the decision to halt prosecutions against Trump while continuing efforts against associates involved in obstruction. Other legal cases, such as the Georgia election interference case, remain stalled or unresolved. Smith's resignation marks the end of his role in a polarizing chapter of U.S. legal and political history.Trump prosecutor Jack Smith resigns from Justice Department | ReutersApple is defending itself against a £1.5 billion ($1.8 billion) class-action lawsuit in the UK, which alleges the company abused its dominance by charging a 30% commission on App Store transactions, unfairly inflating costs for approximately 20 million iPhone and iPad users. The lawsuit, led by British academic Rachael Kent, claims Apple maintains a monopoly over app distribution and imposes restrictive terms that harm developers and consumers alike. Apple argues the case lacks merit, emphasizing that most developers pay no commission and highlighting the benefits of its iOS ecosystem, which prioritizes security and innovation. The company further defends its practices as a legitimate use of its intellectual property, dismissing allegations as an attempt to undermine its rights.This is the first large-scale lawsuit against a tech giant to go to trial under the UK's new class-action regime, with additional cases targeting Apple, Google, Meta, and Amazon expected to follow. A similar $1.1 billion case against Google over Play Store fees is set for later in 2025. The trial will last seven weeks, with Apple's CFO, Kevan Parekh, scheduled to provide testimony.Apple fights $1.8 billion App Store lawsuit in first of UK class actions against tech giants | ReutersThe Biden administration's negotiation of Medicare drug prices under the Inflation Reduction Act revealed the strategic approaches taken by both the Centers for Medicare & Medicaid Services (CMS) and pharmaceutical companies. These closed-door negotiations included legal, commercial, and policy experts on both sides, reflecting the complexity of determining prices for some of Medicare's most expensive drugs. The finalized cuts, announced in August 2024, ranged from 38% to 79%, aiming to generate billions in savings. However, skepticism remains over whether these savings will fully materialize due to offsetting factors.Pharmaceutical companies tailored their delegations to include experts in market access, global pricing, health economics, and portfolio strategy, reflecting their varied priorities. AstraZeneca, for example, sent contract operations specialists as part of its broader lawsuit challenging the program's implementation. Meanwhile, Novartis focused on market access for its heart failure drug, Entresto, expressing concerns about reduced patient access. Other companies, including Merck and AbbVie, redacted participant details, citing proprietary considerations.Legal teams were present at nearly every meeting, underscoring ongoing litigation over the program's constitutionality. Manufacturers have largely been unsuccessful in court, although some have won partial victories. Topics discussed during negotiations, such as clinical value and FDA approvals, offered insights into how both sides justified price cuts. The CMS plans to expand the program with additional drugs in its next negotiation round, which will occur under the incoming Trump administration. President-elect Trump has appointed Mehmet Oz to lead the CMS, signaling potential shifts in how the program is managed. Industry observers see these initial negotiations as a test case for broader reforms in U.S. drug pricing policy.Drug Industry Lawyers, Experts Helped Shape US Drug Price Cuts This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.minimumcomp.com/subscribe

Entresto, Corodil, Cipralex, Amlodipin, Metformin, Viagra, Wegovy. Listen over medicinske præparater, som vi danskere dagligt indtager er nærmest uendelig. Blandt danskere over 65 år får næsten 90 pct. receptpligtig medicin. Staten spenderer godt 16 milliarder kroner årligt på medicin. Torben spørger lytterne, hvilke gode eller dårlige oplevelser de har haft med medicin.See omnystudio.com/listener for privacy information.

What will we pay for the next groundbreaking drug? In episode 4 of our 5-episode series, “Insight Unpacked: American Healthcare and Its Web of Misaligned Incentives,” we explore the trade-off at the heart of pharmaceutical innovation. On this episode, we hear from Kellogg faculty members Amanda Starc and Craig Garthwaite, as well as Boston University School of Law's Kevin Outterson.  Visit the episode page for supplementary materials. 

NEJM 2021:385:1845-55.Background Over two decades had passed since the publications of the seminal trials comparing ACE inhibitors with placebo in post-MI patients with LV dysfunction and congestive heart failure (SAVE, AIRE and TRACE). The VALIANT trial, published in 2003, found that the ARB drug Valsartan was as effective as Captopril in improving survival and reducing cardiovascular morbidity in this patient population. Thus, for many years, a cornerstone of managing post-MI patients with LV dysfunction and heart failure involved afterload reduction with ACE inhibitors or ARBs.Then in 2014, the landscape of heart failure management changed with the publication of the PARADIGM-HF trial which found that Entresto, a drug combining the ARB Valsartan and the neprilysin inhibitor Sacubitril, significantly reduced death and heart failure hospitalizations. We will review PARDIGM-HF later since it enrolled patients with chronic, stable heart failure and not post-MI patients. The rationale for the combination drug is that it simultaneously blocks the renin-angiotensin system and inhibits of the breakdown of several vasoactive peptides including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), serving to enhance vasodilation and reduce blood volume.The PARADISE-MI trial sought to test the hypothesis that early initiation of Sacubitril-Valsartan in post-MI patients with LV dysfunction and congestive heart failure would reduce cardiovascular death or incident heart failure compared to the ACE inhibitor Ramipril.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Adults without a history of heart failure who had a spontaneous MI within 0.5 to 7 days before presentation who had either a LVEF of /= 70 years, diabetes, previous MI, eGFR

First generics of heart failure drug gain approval; mRNA vaccine approved for RSV; CDC make drug recommendation for STI prevention; Advisory Committee vote on MDMA for PTSD; Rinvoq approval expanded

Entresto, Lung Transplants, How to Keep Up with Literature - Lecture to Trainees in Curacao

Episode 154: Heart Failure and GDMTDr. Malave explains the four main medications that are part of the guideline-directed medical therapy of heart failure with reduced ejection fraction. Dr. Arreaza added comments and questions.  Written by Maria Fernanda Malave, MD. Edits by Hector Arreaza, MD.  You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Brief introduction: Heart failure (HF) is a common condition that affects about 23 million people in the world, and it is estimated that 50% of cases are due to heart failure with reduced ejection fraction (HFrEF). It is a major public health concern because of the high morbidity and mortality with a 5-year survival rate of 25% after hospitalization due to HFrEF.In recent years, the management of HFrEF has evolved due to increased evidence in favor of certain medications. Guideline-directed medical therapy (GDMT) is the foundation of medical therapy for these patients, and it is the result of multiple randomized controlled trials and reviews favoring four main drug classes: 1. renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors -ACEi- and angiotensin receptor blockers -ARB), 2. evidence-based β-blockers, 3. mineralocorticoid inhibitors, and 4. sodium-glucose cotransporter 2 inhibitors -SGLT-2i-. The benefit of this therapy is mostly seen when these four groups of medications are used in conjunction. During this episode, we will provide some key elements about the prescription of these medications, but this is only an overview, and you are invited to continue learning from reputable sources.Definitions: HF is defined as the impairment of the heart to meet the metabolic demands of the body. It can be caused by multiple conditions that interfere with the filling up of the heart or conditions that prevent an effective ejection of blood out of the heart. Classification of HFrEF: Based on the EF by echocardiogram, heart failure can be classified as:Heart failure with preserved ejection fraction (HFpEF) when the EF is 50% or more.Heart failure with mildly reduced ejection fraction when EF ranges between 41-49%.Heart failure with reduced ejection fraction (HFrEF) when EF is 40% or less.GDMT: Once we make the diagnosis of HF, it is key to educate our patients and re-educate them every single visit about the importance of guideline-directed medical therapy (GDMT) and lifestyle modifications, because this can change the prognosis and exacerbation rates. Many patients think that since they are feeling well after starting GDMT they can stop it, but that's going to increase exacerbations, hospitalizations, and decrease quality of life. Key points to discuss with patients.First, discuss that GDMT are disease-modifying drugs that regulate the neurohormonal system to stop the progression of the disease. We should explain to our patients that medications should be taken despite feeling well. Also, patients should be educated about regular follow-ups and medication titration. We can even instruct our patients about increasing their furosemide dose if they observe signs of overload, such as a weight increase of 2-3 kgs in 3-4 days, tight rings, socks or bracelets, also Paroxysmal nocturnal dyspnea, dyspnea on exertion, and more.  Second, lifestyle modifications such as: quit smoking and alcohol. Additionally, in general, water restriction between 1.2-1.5L daily, salt restriction (there is no official recommendation about how many grams, but in general we recommend less than 2g daily). Third, it is highly recommended to do aerobic exercise that produces mild dyspnea since this improves cardiovascular capacity and decreases hospitalization risk. Patients should be encouraged to have their annual influenza vaccine and pneumococcal vaccine according to their own immunization schedule. According to the AFP journal, in September 2022, researchers found a clinically and statistically significant reduction in all-cause mortality for patients who received an influenza vaccine right after an MI, with a number needed to treat of 50, the effectivity of the vaccine may vary by season.GDMT, groups of medications:What are the basic medications any patient with HF should be on? At least, patients should be on angiotensin receptor blockers ARBs/ACEIs and Beta-blockers. Let's keep in mind that beta-blockers should be given cautiously in cases of exacerbation, but in general low doses are safe. We also have the angiotensin receptor/neprilysin inhibitors (ARNIs), a group of medications whose representative is the combination of sacubitril/valsartan, aka Entresto®. This medication should be the target once ARBs/ACEIs are tolerated. ARBs/ACEIs/ARNIs should be discontinued in the setting of advanced CKD, with a GFR of 30 or less. This applies to other medications used in HF such as SGLT-2 and mineralocorticoid receptor antagonist (MRA, such as spironolactone/eplerenone). Remember that SGLT-2 inhibitors should be started regardless diabetes status, and BB are safe in the setting of CKD. We also have other groups that are considered safe in patients with advanced CKD such as hydralazine/isosorbide dinitrate (combined or not), which are used in African Americans whose BP and HF symptoms do not improve with maximally tolerated dose of ARBs/ACEIs + BB.Ivabradine: Let's not forget about ivabradine, which is an SA node inhibitor like BB. Patients need to meet criteria such as a maximally tolerated dose of beta-blocker, heart rate of a least 70 or more and being on normal sinus rhythm to be started on this medication. Ivabradine does not improve survival as BB do, so even though they are not contraindicated in HF exacerbation, BB are still preferred since ivabradine does not decrease mortality.Titration and follow-ups in the HF management:-ARBs/ACEIs/ARNIs should be titrated approx. Q2 weeks until the maximally tolerated dose is achieved, ARNI should be titrated up Q2-4weeks. With these medications, we should monitor BP, potassium levels and Glomerular Filtration Rate (GFR). -BB can also be titrated up Q2weeks until the maximally tolerated dose is achieved. HR, BP and signs of congestion should be observed in patients on BB. Same for hydralazine/isosorbide, with BP follow-up. -MRA, such as spironolactone/eplerenone, these meds can be added in patients who remain symptomatic despite maximally tolerated doses of “ARBs or ACEIs or ARNIs” plus Beta-blockers. For MRA, potassium level, and GFR should be monitored every 2-3 days after initiation, 7 days after titration, monthly for 3 months, and then Q3 months. To start a patient on MRA, K+ must be lower than 5.Patients with HF should be followed up at least in a 2-week interval either via telephone, telemedicine, or clinic visit to assess symptoms, vital signs, bloodwork and to perform a physical exam. Monitoring EF: After 3-6 months of the patient´s stabilization, we should reorder an echo, EKG, BNP and Basic Metabolic Panel. The ejection fraction improves in all patients after GDMT initiation and compliance, and in some patients, this improvement is very significant, so we need to reassess EF after stabilization. Comorbidities: Also, let´s keep in mind that most of the patients have associated comorbidities such as Afib, diabetes, valve disease, or anemia. These comorbidities must be addressed either by starting anticoagulation, adjusting anti-diabetes medications, starting iron, or referring to cardiology if a valve replacement is needed.When to refer to Cardiology? Some patients will qualify for device therapy (ICD) as a primary prevention for ventricular arrhythmias that can degenerate either into torsades or ventricular fibrillation. These patients must be symptomatic, at least in 3 months of maximally tolerated GDMT, and EF between 30-35%. Symptomatic

The federal government announced it has selected the first 10 drugs it will negotiate for lower prices with pharmaceutical firms. The Centers for Medicare and Medicaid Services selected the drugs, all of which are covered under Medicare Part D. The 10 drugs — Eliquis, Jardiance, Xarelto, Januvia, Farxiga, Entresto, Enbrel, Imbruvica, Stelara and Fiasp/NovoLog — accounted for .5 billion of total costs for Medicare's Part D program from June 2022 to May 2023. Medicare plans to use the cost savings to place a ,000 limit on enrollees' of out-of-pocket expenditures for drugs starting in 2026. But it could delay innovation...Article Link

Mark Twain once said, “Never put off till tomorrow, what you can do the day after tomorrow.” As an antidote to that Ralph welcomes Professor Piers Steel, author of “The Procrastination Equation: How to Stop Putting Things Off and Start Getting Stuff Done.” Plus, Ralph urges listeners to sign up for The Capitol Hill Citizen Association, another way to organize citizens to put pressure on the branch of our government where things must get done, the United States Congress.  Dr. Piers Steel is one of the world's leading researchers and speakers on the science of motivation and procrastination. Dr. Steel is a professor in the Organizational Behaviour and Human Resources area at the University of Calgary, and is the Brookfield Research Chair at the Haskayne School of Business. He is the author of The Procrastination Equation: How to Stop Putting Things Off and Start Getting Stuff Done.The root of procrastination is impulsiveness. Impulsiveness is valuing the now more than the later… We're designed to value the now. And this was really adaptive for a long time. It's not a bad trait. It's just that we've designed a world to take advantage of every little flaw that we have in our decision-making system.Dr. Piers SteelYou have to deal with yourself as an imperfect, flawed creature and deal with the reality of that. We're not robotic angels of perfection. We have limitations. And when I actually act within my limitations, I get stuff done.Dr. Piers SteelWe're superstars of self-control in the animal kingdom. We're able to hunt and kill most anything because we're willing to actually put in the delay of gratification. That's really what makes us great. But we're still not ready for things that are happening even a year off, much less five or ten.Dr. Piers SteelMore people will listen to what we just said about becoming part of the Capitol Hill Citizen Association and say to themselves, “I'm going to get around to doing that,” than the actual number of people who do it in a prompt period of time. So it would be very good to listen to Professor Steel's suggestions and read his book, because we cannot afford procrastinatory citizens. We have a procrastinatory Congress, and the citizens have got to get them to anticipate, to foresee, to forestall so many of the omnicidal urgencies that are coming at our country and other countries around the world.Ralph NaderTo become a member of the Capitol Hill Citizen Association, click here.In Case You Haven't Heard with Francesco DeSantis1. On August 28th, 20 groups – ranging from Left-wing anti-war organizations like Veterans for Peace to Right-leaning government transparency groups like R Street Institute – sent a letter to the Chairs and Ranking Members of the House and Senate Armed Services Committees demanding they maintain Rep. Jamaal Bowman's Cost of War amendment in the final National Defense Authorization Act. This provision “requires public disclosure about the cost of the U.S.' overseas military footprint and gives the American people greater transparency on military spending.” Hopefully, the left-right consensus on this issue is enough to maintain this amendment.2. In other Pentagon news, the Intercept reports that Rep. Matt Gaetz, Republican of Florida, has introduced an amendment demanding the Pentagon “collect information on trainees who overthrow their governments,” following the recent spate of coups in Africa. Gaetz told the Intercept “The Department of Defense, up until this point, has not kept data regarding the people they train who participate in coups to overthrow democratically elected — or any — governments.” This could become a flashpoint as Congress prepares to consider the 2024 NDAA when it returns from recess in September.3. As expected, tensions are running high in Guatemala following the upset victory of anti-corruption crusader Bernardo Arevalo. Opponents of Arevalo had urged the country's electoral tribunal to suspend his Semilla party on dubious legal grounds, which the tribunal resisted hewing to the letter of the law which dictated such actions could not be taken during the electoral process. After the election however, the party was officially suspended. Now, Reuters reports that suspension has been revoked, following a mass mobilization of Arevalo supporters in Guatemala City. It seems unlikely however that Arevalo's political opponents will accept his victory without a fight.4. In a dangerous, anti-free speech move, the Attorney General of Georgia has filed RICO indictments against 42 individuals involved with the Stop Cop City protest movement, the Atlanta Community Press Collective reports. This is the latest in a long line of attempts to quash opposition to the project, which has so far included trumped up domestic terrorism charges and arrests for handing out flyers.  5. Bloomberg reports that President Biden and Brazilian President Lula will jointly call for new worker protections at the upcoming General Assembly of the United Nations. While the article notes the two leaders have been “at odds” over China and Russia, they align on the topic of labor unionization. The two presidents have found common ground before, such as on the issue of climate change.6. Visual Effects workers at Disney have filed for unionization, per the Hollywood Reporter. Approximately 80% of VFX staff have already signed union cards, demanding an NLRB election and representation by the International Alliance of Theatrical Stage Employees or IATSE. This comes on the heels of a similar announcement by VFX workers at Marvel, a Disney subsidiary. In recent years. studios have increasingly relied on VFX workers in a rather blatant attempt to cut costs, as VFX workers have generally been non-union.7. At long last, the Department of Health and Human Services has announced the first ten drugs that will be subject to Mecicare negotiations to bring down prices. These are: Eliquis, Jardiance, Xarelto, Januvia Farxiga, Entresto, Enbrel, Imbruvica, Stelara and – crucially – several brands of insulin. HHS noted that “These selected drugs accounted for $50.5 billion in total [Medicare] Part D gross covered prescription drug costs, or about 20%, of total Part D gross between June 1, 2022 and May 31, 2023.”8. The Washington Post reports Acting Labor Secretary Julie Su has proposed new overtime rules intended to “extend overtime pay to an additional 3.6 million salaried white-collar workers in the United States.” According to current rules, workers are exempt from overtime if they make over $35,568 per year; the new rules would extend to workers making under $55,000 annually. If implemented, this would mean a whole new class of workers would be eligible for time-and-a-half pay if they work more than 40 hours per week.9. Per Republic Report: “The U.S. Department of Education announced…that it is cancelling $72 million in student loan obligations for more than 2,300 former students who attended for-profit Ashford University between 2009 and 2020.” Yet, even now the shady operators behind Ashford may still be able to squeeze money out of the taxpayers via a convoluted buyout by the University of Arizona Global Campus. Still, this marks a significant victory in a legal battle that has raged for over a decade, with Senator Tom Harkin of Iowa calling Ashford a “complete scam” all the way back in 2011.10. Finally, in more debt related news, the Philadelphia Inquirer has published a piece detailing how the nonprofit RIP Medical Debt was able to purchase – and forgive – over $1.6 million in medical debt. As the piece explains “When hospitals or physician groups have delinquent debts they have little chance of collecting on, they'll typically go to what's called the secondary market and sell their portfolios for pennies on the dollar.” It was on this secondary market that RIP Medical Debt was able to buy $1.6 million worth of debt for just $17,000. In celebration, “30 proud, self-described gutter-pagan, mostly queer dirtbags in their early 30s,” gathered for a ritual burning of an oversized medical bill. Someone chanted “debt is hell” and the crowd responded “let it burn.” Get full access to Ralph Nader Radio Hour at www.ralphnaderradiohour.com/subscribe

Politisches Risiko und hoch im Kurs Wer meine Podcasts Börsenminute und GELDMEISTERIN schon länger verfolgt, weiß, dass ich Pharmaaktien für mein Langfristportfolio als eine wichtige Säule favorisiere und das tue ich auch weiterhin. Nur: durch die letzten starken Anstiege vor allem beim skandinavischen Shootingstar Novo Nordisk (Stichwort Diabetesmedikamente, die als Abnehmpille Furore machen) bin ich dabei, mein Pharma-Portfolio zu Rebalancieren, sprich einen Teil der Kursraketen zu verkaufen, um den Gesundheitstitel-Anteil und so mein Klumpenrisiko wieder zu reduzieren. Oder mir maximal die jüngsten Rohrkrepierer wie Roche zumindest genauer anzuschauen. Denn Risiko-behaftet sind Gesundheitstitel in jedem Fall und da denke ich nicht einmal an etwaige Nebenwirkungen, die in der Vergangenheit schon des Öfteren zu sündteuren Klagen geführt haben. Nein, es sind die Bewertungen, die ich teilweise nicht mehr gesund finde. Eli Lilly zum Beispiel hat in den letzten fünf Jahren um 430 Prozent zugelegt. Das Kurs-Gewinn-Verhältnis liegt bei knapp 56. Soll heißen, ich muss - aus heutiger Sicht wohlgemerkt - 56 Jahre warten, bis ich den Preis für die Aktie hereinverdient habe. Das dauert mir zu lange, auch wenn ich ihnen viel Gewinnsteigerungspotenzial noch zutraue. Man sollte keinesfalls das politische Risiko der Branche unterschätzen. Joe Biden hat gerade zehn Medikamente auf seiner Watchlist, die seinen „Inflation Reduction Act“ konterkarieren. Hier wird gerade mit Bristol-Myers, Johnson & Johnsohn, Merck, Novo Nordisk, Boehringer Ingelheim, Novartis, Amgen & Co gefeilscht, welche Preise das staatliche Gesundheitssystem künftig nur noch für die Arznei bereit ist zu bezahlen und das ist nicht unerheblich. Zum einen, schreibt die Financial Times, droht ihnen eine Besteuerung von 65 bis 95 Prozent, zum anderen ein Ausschluss aus dem Gesundheitsprogramm Medicare, was tragisch wäre, da es teilweise zu 50 Prozent ihre Umsätze in den USA sichert. Die konkreten Medikamente, deren Preise für Biden´s Geschmack zu hoch sind, findet ihr hier im Beipackzettel zu dieser Börsenminute: • Eliquis von Bristol-Myers Squibb (NYSE:BMY); • Jardiance von Boehringer Ingelheim; • Xarelto von Johnson & Johnson (NYSE:JNJ); • Januvia von Merck (NYSE:MRK); • Farxiga von AstraZeneca (NASDAQ:AZN); • Entresto von Novartis (NYSE:NVS); • Enbrel von Amgen (NASDAQ:AMGN); • Imbruvica von AbbVie (NYSE:ABBV); • Stelara von Janssen (im Besitz von JNJ); • Fiasp, Fiasp FlexTouch, Fiasp PenFill, NovoLog, NovoLog FlexPen, NovoLog PenFill von Novo Nordisk (NYSE:NVO). Rechtshinweis: Dies ist die Meinunung der Autorin und keine Anlageempfehlung. Was ihr daraus macht ist Eure Sache, Julia Kistner übernimmt hierfür keine Haftung. #Börse #investment #Pharmatitel #Inflationreductionact #Aktien #podcast Foto: Unsplash

Florida Gov and GOP 2024 also-ran Ron DeSantis looks to lead in wake of violence and major hurricane | Former SC Gov and UN Ambassador under President Trump, Nikki Haley is having a moment, kind of | President Biden names first 10 drugs subject to negotations with Medicare | 60th anniversary of the March on WashingtonSong playsIntro by hostWelcome to Heartland Pod Wednesday!Support this show and all the work in the Heartland POD universe by going to heartlandpod.com and clicking the link for Patreon, or go to Patreon.com/HeartlandPod to sign up. Membership starts at $1/month, with even more extra shows and special access at the higher levels. No matter the level you choose, your membership helps us create these independent shows as we work together to change the conversation.Alright! Let's get into it: Hurricane in Florida / Shooting in FloridaPOLITICO: DeSantis knows how to handle a hurricane. The racist shooting poses a bigger dilemma.A racially-motivated Jacksonville tragedy, couple with a looming storm, pose big tests for the governor.Florida Gov. Ron DeSantis, center and his wife Casey, right, bow their heads during a prayer.Florida Gov. Ron DeSantis (center) and his wife Casey bow their heads during a prayer at a vigil for the victims of Saturday's mass shooting on Sunday, Aug. 27, 2023, in Jacksonville. | John Raoux/AP PhotoBy KIMBERLY LEONARD08/28/2023 04:14 PM EDTUpdated: 08/28/2023 05:12 PM EDTMIAMI — Florida Gov. Ron DeSantis' handling of back-to-back crises — a racist mass shooting and a potentially catastrophic hurricane — could help burnish his image as a can-do, effective governor or further damage his standing with Black Americans who have grown livid over his policies.Already, DeSantis' attempts to show leadership in the immediate aftermath of the Saturday shooting were poorly received by some Black lawmakers, Democrats and residents in Florida. In the hours after a 21-year-old white man killed three Black Floridians near a historically Black college in Jacksonville, several state Democrats blamed DeSantis, who is running for president, for creating an environment, through policies such as loosening gun laws and ending diversity programs, that helped hate fester.DeSantis has condemned the shooting and said “targeting people due to their race has no place in this state of Florida.” But attending a Sunday night vigil in Jacksonville, he was jeered and booed by people who had come out to remember the victims. At one point, a Jacksonville Democratic councilmember stepped in to calm the crowd, urging people to “put parties aside.” Later during the event, a pastor took issue with DeSantis describing the gunman as a “scumbag,” and said he should have used the word “racist” instead.The vigil stood in contrast to press conferences in Tallahassee on Sunday and Monday, when DeSantis appeared visibly tired but spoke authoritatively about preparations overseeing Tropical Storm Idalia, which is forecast to become a major hurricane. He canceled campaign appearances and fundraisers, and told Floridians Sunday they could “rest assured” because “I am here” and would “get the job done.”DeSantis says politics won't interfere with storm response“He needs to be in Florida for as long as it takes,” said Adam Hollingsworth, the former chief of staff to Sen. Rick Scott (R-Fla.), who served as governor before DeSantis. “His presidential ambitions could be a distraction, but first Gov. DeSantis has to dance with the one who brought him. Right now, that's the people of Florida.”Though the shooting and looming storm are taking DeSantis away from campaigning for president following a high-profile debate, they'll also allow voters and donors to see the governor at work leading the hurricane response, letting the public assess how he balances multiple priorities, displays empathy and projects leadership in moments of tragedy. At the same time, the shooting has shined a spotlight on DeSantis' record and vulnerabilities on race, one of the areas for which he has faced the most criticism and controversy as governor.In times of tragedy, opponents are “looking for a misstep,” acknowledged Craig Fugate, who led Florida's emergency division under Gov. Jeb Bush and oversaw FEMA during the Obama administration.“They're looking for something to go wrong — particularly for the opponents; they're looking for something to capitalize on,” Fugate said.DeSantis began his Monday morning hurricane preparedness press conference by first addressing the mass shooting. He pledged $1 million in security funding to Edward Waters University, a historically Black university that the gunman is believed to have initially targeted, as well as $100,000 toward a charity for the families of the victims. He also deployed state law enforcement officials to evaluate the campus' security and make additional recommendations, pledging to continue to assist in the “days and weeks ahead.”But many Democrats in the state panned his response. They pointed to laws he enacted in Florida to carve up representation in a Black-majority district that eventually led a Black Democratic congressman, Rep. Al Lawson, to lose his seat. They also pointed to his policies, approved by the GOP-led Legislature, banning what he calls “critical race theory” in schools, as well as his defense of a public school curriculum on Black history that required middle-school teachers to instruct that enslaved people “developed skills which, in some instances, could be applied for their personal benefit.”Florida Minority House Leader Fentrice Driskell, a Black Democrat of Tampa, said it was “absolutely” the right decision for DeSantis to attend the vigil but added that she didn't want to give him a pass.“The reality is, a number of wrongheaded decisions about the state of Florida, and who we are as a people, I think contributed to this charged political climate that resulted in the violence that we saw,” Driskell said in an interview.The accused gunman, identified as Ryan Palmeter, had a racist manifesto and drew swastikas on his weapons. He also had a history of mental illness, having been involuntarily institutionalized for emergency mental health services as a teenager, police said.During DeSantis' vigil remarks Sunday, Democratic state Rep. Angela Nixon, who represents the district where the shooting took place, could be seen glaring at the governor in videos and photos widely shared on social media.“We feel the same,” the NAACP wrote on X, the social media platform formerly known as Twitter.AXIOS: Biden set to name first 10 drugs subject to Medicare negotiations.The blood-thinners Eliquis and Xarelto are among the 10 prescription medicines the Biden administration will seek lower Medicare prices for as part of a new program allowing the government to negotiate drug prices for America's seniors.Why it matters: The administration's landmark announcement Tuesday detailed the first-ever set of drugs subject to Medicare price negotiations, a longtime Democratic priority included in last year's Inflation Reduction Act over drug companies' fervent objections.Other drugs up for negotiation include:Jardiance, a diabetes drug.Januvia, also for diabetes.Farxiga, another diabetes drug.Entresto, for heart failure.Enbrel, for arthritis and psoriasis.Imbruvica, a blood cancer drug.Stelara, used on psoriasis, Crohn's disease and other illnesses.Fiasp, also used for diabetes.Of note: Insulin is already subject to a $35 monthly co-pay cap for Medicare prescription drug plan enrollees under a different provision of the IRA.State of play: The drugs' manufacturers will have just over a month to decide whether to participate in negotiations — which the industry is battling in court — or sit out the process, at the risk of significant financial penalty.Drugmakers who refuse to negotiate with Medicare face an excise tax of up to 95% of their U.S. sales, or they can withdraw their drugs from Medicare and Medicaid coverage, shutting them out of huge markets.What they're saying: "The cancer moonshot will not succeed if this administration continues to dismantle the innovation rocket we need to get there," Stephen Ubl, CEO of industry trade group PhRMA, said in a statement following the release of the list.Zoom out: The medicines up for negotiation were chosen from a list of the 50 products with the highest spending in Medicare's prescription drug program, Part D.The selected drugs accounted for 20% of Part D prescription costs between June 1, 2022 and May 31, 2023, according to the Health and Human Services Department.Some of the highest-cost Medicare drugs were not eligible for this round of negotiations, either because they still have market exclusivity, they're the only option for a rare disease or another factor.The prices won't take effect before the 2024 elections, but Democrats are expected to tout the negotiations, along with other drug cost reforms in the IRA, as part of their campaign messaging.What's next: The Centers for Medicare and Medicaid Services will submit price offers to the drug companies by Feb. 1, with negotiations continuing until next August.CMS will publish the drugs' final maximum fair prices by Sept. 1, 2024, and prices will go into effect in 2026.What we're watching: Ongoing legal challenges could draw out or halt the negotiation process.Drugmakers and allied groups have already filed eight lawsuits against the Medicare drug negotiation process, and more lawsuits could follow Tuesday's announcement.President Biden and his health officials committed this morning to fighting industry lawsuits."Let me be clear: I am not backing down. There is no reason why Americans should be forced to pay more than any developed nation for life-saving prescriptions just to pad Big Pharma's pockets," Biden said in a statement.Nikki HaleyDAILY BEAST: Is it time for Republicans to take Nikki Haley seriously?According to a new Emerson College Polling survey, “Haley saw the largest increase in support among Republican candidates, jumping 5 points from 2 percent to 7 percent” following last week's debate.“Nikki Haley's support increased from about 2 percent to 9 percent among voters over 50 [years of age],” said Spencer Kimball, executive director of Emerson College Polling, “while Trump's support dropped within this age group from about 56 percent to 49 percent after the debate.”Republican Debaters Agreed on One Thing: They Hate Vivek RamaswamyThis jump is modest, inasmuch as it still leaves Haley in the single digits. But it's also no outlier. According to a poll conducted by The Washington Post, FiveThirtyEight, and Ipsos released last Thursday, voters were persuaded to at least give her a second look. “Pre-debate, 29 percent of GOP primary voters who watched the debate said they were considering voting for her,” according to the survey, “and that increased to 46 percent after the debate.”So how did she do it? Haley caught our attention by being first to hit Trump (from the right), when she criticized him for “adding eight trillion to our debt.” This surprised everyone, demonstrated courage, and put to rest the notion that she is merely running to be Trump's vice president.Haley also staked out a strong position on abortion. While stressing her pro-life beliefs, she made the pragmatic case that a federal abortion ban would require 60 votes. Instead, Haley urged Republicans to focus on consensus issues, like banning late-term abortions, making sure contraception is widely available, and supporting adoption as an alternative.Trump's former veep, Mike Pence, who supports a 15-week federal ban on abortion, took umbrage with this. “Nikki, you're my friend, but consensus is the opposite of leadership,” Pence scolded. (As the Never Trump conservative writer Jonah Goldberg has pointed out on his podcast, building consensus is often a key attribute of leadership.)The Republican Debate Was a Futile Pudding Wrestling MatchThis exchange, like others during that same debate, made it clear that in a general election Nikki Haley would likely be Joe Biden's most challenging opponent.Having served as governor of South Carolina and ambassador to the United Nations, she has the experience needed for the office. She also has sharp elbows. (“You have no foreign policy experience and it shows,” she told Vivek Ramaswamy.)At 51, Haley would present a stark contrast in terms of generational change, assuming that Joe Biden was still the Democratic nominee. And (unlike others) she is not staking out an abortion position that might render her effectively unelectable, should she become the Republican nominee.Haley (who frequently cites Margaret Thatcher's line, “If you want something said, ask a man. If you want something done, ask a woman”) was the only woman on that stage. Her identity, temperament, and policy positions could help chip away at the gender gap that has only grown in recent years.The obvious caveat here is that all of these things would make Haley a great candidate to beat Joe Biden if she somehow wins the Republican nomination. But that's an awfully big “if.”Kareem Abdul-Jabbar: GOP Debate Showed How Not to Pick a PresidentHaley's answer to this is to make the electability argument: “We have to face the fact that Trump is the most disliked politician in America,” she—and she, alone—averred during last week's debate.But will that dog hunt?Right now, the electability argument isn't persuading Republicans to jump off the Trump bandwagon, even though that argument is likely the only one that could ever work. At some point (perhaps after Donald Trump goes on trial and it's too late), Republicans might be convinced that, as entertaining as Trump is, he simply can't win.Based on all of this, you might expect me to suggest that it's time to clear the field—to rally every freedom conservative, Reagan Republican, and Never Trump conservative to coalesce around Haley as the GOP's last, best hope.Some of my colleagues are already there. The New York Times columnist David Brooks, for example, declared last week that “Wednesday's debate persuaded me that the best Trump alternative is not [Tim] Scott, it's Nikki Haley.”But here's my problem. Haley has been all over the map for years now. One day she's courageous and impressive, and the next day she's a pathetic Trump toady.Haley is a political chameleon, which makes me reluctant to ever trust her again.Trump and Ramaswamy Show Us How the Worst Get to the TopOn the other hand, anyone looking for purity (as it pertains to Trump) can also dismiss Pence and Chris Christie—both of whom supported Trump until Jan. 6—and a vast swath of today's leading Never Trumpers. As the Good Book says, “Who then can be saved?”Nikki Haley's got a long way to go before she clears the not-Trump lane of candidates, much less taking on the final boss himself. And though nothing has yet made a dent in Trump's domination of the GOP voter base, he's never run as a candidate on trial before. But the whole 91-felony indictment thing might just do the trick.If Haley can prove herself by stringing together two or three of these kinds of courageous performances—in which she not only characterizes Trump as the guy who already lost to Biden, but also that she's as real a conservative as any of the other contenders—there is a path to success.It's hardly guaranteed, and as I've noted, courage comes and goes with Haley. But in the “Matt Lewis primary,” you can count me among the 46 percent who are now considering voting for her.Read more at The Daily Beast.SEMAFOR: Nikki Haley's abortion message could catch on in the GOPMorgan Chalfant and Kadia GobaRepublicans worried about Democrats leveraging abortion (again) to make gains in 2024 want GOP candidates to take a page out of Nikki Haley's debate prep playbook.Haley dismissed the idea that a 15-week national abortion ban could pass through Congress. Instead, she argued the focus should be on finding “consensus” around banning “late-term abortions,” sustaining access to contraception, allowing doctors who don't support abortion refuse to perform them, and preventing women who get abortions from being penalized.Defeated Michigan gubernatorial candidate Tudor Dixon bluntly said on Fox News that Republicans would lose the messaging war in 2024 unless they followed Haley's “perfect response” in the debate.“No one really understood how important abortion would be in 2022 because no one had run in a post-Roe world, so we suddenly got attacked, viciously attacked, by the Democrats, and it is a winning message for them,” she said. Gov. Gretchen Whitmer highlighted Dixon's opposition to rape exceptions in abortion bans in their contest, which took place alongide a ballot initiative guaranteeing abortion rights that passed by a wide margin.“The only candidate on the stage that talked about how we should protect women and not demonize them was Nikki Haley,” Rep. Nancy Mace, R-S.C. said Sunday on CBS of the first GOP presidential debate. “And that is a message that we have to carry through. We have to be pro-woman and pro-life. You cannot go after women and attack them because they make a choice that you don't like or don't agree with.”And Rep. George Santos, R-N.Y., who represents a district President Biden won in 2020, told Semafor at a watch party last week: “She had probably the best-packaged message on abortion that I've heard, I want to say, in my entire adult life.”Haley might have won herself some fans, but her position wasn't a favorite within the anti-abortion movement, which has rallied around a 15-week federal ban as a minimum ask for candidates.

Florida Gov and GOP 2024 also-ran Ron DeSantis looks to lead in wake of violence and major hurricane | Former SC Gov and UN Ambassador under President Trump, Nikki Haley is having a moment, kind of | President Biden names first 10 drugs subject to negotations with Medicare | 60th anniversary of the March on WashingtonSong playsIntro by hostWelcome to Heartland Pod Wednesday!Support this show and all the work in the Heartland POD universe by going to heartlandpod.com and clicking the link for Patreon, or go to Patreon.com/HeartlandPod to sign up. Membership starts at $1/month, with even more extra shows and special access at the higher levels. No matter the level you choose, your membership helps us create these independent shows as we work together to change the conversation.Alright! Let's get into it: Hurricane in Florida / Shooting in FloridaPOLITICO: DeSantis knows how to handle a hurricane. The racist shooting poses a bigger dilemma.A racially-motivated Jacksonville tragedy, couple with a looming storm, pose big tests for the governor.Florida Gov. Ron DeSantis, center and his wife Casey, right, bow their heads during a prayer.Florida Gov. Ron DeSantis (center) and his wife Casey bow their heads during a prayer at a vigil for the victims of Saturday's mass shooting on Sunday, Aug. 27, 2023, in Jacksonville. | John Raoux/AP PhotoBy KIMBERLY LEONARD08/28/2023 04:14 PM EDTUpdated: 08/28/2023 05:12 PM EDTMIAMI — Florida Gov. Ron DeSantis' handling of back-to-back crises — a racist mass shooting and a potentially catastrophic hurricane — could help burnish his image as a can-do, effective governor or further damage his standing with Black Americans who have grown livid over his policies.Already, DeSantis' attempts to show leadership in the immediate aftermath of the Saturday shooting were poorly received by some Black lawmakers, Democrats and residents in Florida. In the hours after a 21-year-old white man killed three Black Floridians near a historically Black college in Jacksonville, several state Democrats blamed DeSantis, who is running for president, for creating an environment, through policies such as loosening gun laws and ending diversity programs, that helped hate fester.DeSantis has condemned the shooting and said “targeting people due to their race has no place in this state of Florida.” But attending a Sunday night vigil in Jacksonville, he was jeered and booed by people who had come out to remember the victims. At one point, a Jacksonville Democratic councilmember stepped in to calm the crowd, urging people to “put parties aside.” Later during the event, a pastor took issue with DeSantis describing the gunman as a “scumbag,” and said he should have used the word “racist” instead.The vigil stood in contrast to press conferences in Tallahassee on Sunday and Monday, when DeSantis appeared visibly tired but spoke authoritatively about preparations overseeing Tropical Storm Idalia, which is forecast to become a major hurricane. He canceled campaign appearances and fundraisers, and told Floridians Sunday they could “rest assured” because “I am here” and would “get the job done.”DeSantis says politics won't interfere with storm response“He needs to be in Florida for as long as it takes,” said Adam Hollingsworth, the former chief of staff to Sen. Rick Scott (R-Fla.), who served as governor before DeSantis. “His presidential ambitions could be a distraction, but first Gov. DeSantis has to dance with the one who brought him. Right now, that's the people of Florida.”Though the shooting and looming storm are taking DeSantis away from campaigning for president following a high-profile debate, they'll also allow voters and donors to see the governor at work leading the hurricane response, letting the public assess how he balances multiple priorities, displays empathy and projects leadership in moments of tragedy. At the same time, the shooting has shined a spotlight on DeSantis' record and vulnerabilities on race, one of the areas for which he has faced the most criticism and controversy as governor.In times of tragedy, opponents are “looking for a misstep,” acknowledged Craig Fugate, who led Florida's emergency division under Gov. Jeb Bush and oversaw FEMA during the Obama administration.“They're looking for something to go wrong — particularly for the opponents; they're looking for something to capitalize on,” Fugate said.DeSantis began his Monday morning hurricane preparedness press conference by first addressing the mass shooting. He pledged $1 million in security funding to Edward Waters University, a historically Black university that the gunman is believed to have initially targeted, as well as $100,000 toward a charity for the families of the victims. He also deployed state law enforcement officials to evaluate the campus' security and make additional recommendations, pledging to continue to assist in the “days and weeks ahead.”But many Democrats in the state panned his response. They pointed to laws he enacted in Florida to carve up representation in a Black-majority district that eventually led a Black Democratic congressman, Rep. Al Lawson, to lose his seat. They also pointed to his policies, approved by the GOP-led Legislature, banning what he calls “critical race theory” in schools, as well as his defense of a public school curriculum on Black history that required middle-school teachers to instruct that enslaved people “developed skills which, in some instances, could be applied for their personal benefit.”Florida Minority House Leader Fentrice Driskell, a Black Democrat of Tampa, said it was “absolutely” the right decision for DeSantis to attend the vigil but added that she didn't want to give him a pass.“The reality is, a number of wrongheaded decisions about the state of Florida, and who we are as a people, I think contributed to this charged political climate that resulted in the violence that we saw,” Driskell said in an interview.The accused gunman, identified as Ryan Palmeter, had a racist manifesto and drew swastikas on his weapons. He also had a history of mental illness, having been involuntarily institutionalized for emergency mental health services as a teenager, police said.During DeSantis' vigil remarks Sunday, Democratic state Rep. Angela Nixon, who represents the district where the shooting took place, could be seen glaring at the governor in videos and photos widely shared on social media.“We feel the same,” the NAACP wrote on X, the social media platform formerly known as Twitter.AXIOS: Biden set to name first 10 drugs subject to Medicare negotiations.The blood-thinners Eliquis and Xarelto are among the 10 prescription medicines the Biden administration will seek lower Medicare prices for as part of a new program allowing the government to negotiate drug prices for America's seniors.Why it matters: The administration's landmark announcement Tuesday detailed the first-ever set of drugs subject to Medicare price negotiations, a longtime Democratic priority included in last year's Inflation Reduction Act over drug companies' fervent objections.Other drugs up for negotiation include:Jardiance, a diabetes drug.Januvia, also for diabetes.Farxiga, another diabetes drug.Entresto, for heart failure.Enbrel, for arthritis and psoriasis.Imbruvica, a blood cancer drug.Stelara, used on psoriasis, Crohn's disease and other illnesses.Fiasp, also used for diabetes.Of note: Insulin is already subject to a $35 monthly co-pay cap for Medicare prescription drug plan enrollees under a different provision of the IRA.State of play: The drugs' manufacturers will have just over a month to decide whether to participate in negotiations — which the industry is battling in court — or sit out the process, at the risk of significant financial penalty.Drugmakers who refuse to negotiate with Medicare face an excise tax of up to 95% of their U.S. sales, or they can withdraw their drugs from Medicare and Medicaid coverage, shutting them out of huge markets.What they're saying: "The cancer moonshot will not succeed if this administration continues to dismantle the innovation rocket we need to get there," Stephen Ubl, CEO of industry trade group PhRMA, said in a statement following the release of the list.Zoom out: The medicines up for negotiation were chosen from a list of the 50 products with the highest spending in Medicare's prescription drug program, Part D.The selected drugs accounted for 20% of Part D prescription costs between June 1, 2022 and May 31, 2023, according to the Health and Human Services Department.Some of the highest-cost Medicare drugs were not eligible for this round of negotiations, either because they still have market exclusivity, they're the only option for a rare disease or another factor.The prices won't take effect before the 2024 elections, but Democrats are expected to tout the negotiations, along with other drug cost reforms in the IRA, as part of their campaign messaging.What's next: The Centers for Medicare and Medicaid Services will submit price offers to the drug companies by Feb. 1, with negotiations continuing until next August.CMS will publish the drugs' final maximum fair prices by Sept. 1, 2024, and prices will go into effect in 2026.What we're watching: Ongoing legal challenges could draw out or halt the negotiation process.Drugmakers and allied groups have already filed eight lawsuits against the Medicare drug negotiation process, and more lawsuits could follow Tuesday's announcement.President Biden and his health officials committed this morning to fighting industry lawsuits."Let me be clear: I am not backing down. There is no reason why Americans should be forced to pay more than any developed nation for life-saving prescriptions just to pad Big Pharma's pockets," Biden said in a statement.Nikki HaleyDAILY BEAST: Is it time for Republicans to take Nikki Haley seriously?According to a new Emerson College Polling survey, “Haley saw the largest increase in support among Republican candidates, jumping 5 points from 2 percent to 7 percent” following last week's debate.“Nikki Haley's support increased from about 2 percent to 9 percent among voters over 50 [years of age],” said Spencer Kimball, executive director of Emerson College Polling, “while Trump's support dropped within this age group from about 56 percent to 49 percent after the debate.”Republican Debaters Agreed on One Thing: They Hate Vivek RamaswamyThis jump is modest, inasmuch as it still leaves Haley in the single digits. But it's also no outlier. According to a poll conducted by The Washington Post, FiveThirtyEight, and Ipsos released last Thursday, voters were persuaded to at least give her a second look. “Pre-debate, 29 percent of GOP primary voters who watched the debate said they were considering voting for her,” according to the survey, “and that increased to 46 percent after the debate.”So how did she do it? Haley caught our attention by being first to hit Trump (from the right), when she criticized him for “adding eight trillion to our debt.” This surprised everyone, demonstrated courage, and put to rest the notion that she is merely running to be Trump's vice president.Haley also staked out a strong position on abortion. While stressing her pro-life beliefs, she made the pragmatic case that a federal abortion ban would require 60 votes. Instead, Haley urged Republicans to focus on consensus issues, like banning late-term abortions, making sure contraception is widely available, and supporting adoption as an alternative.Trump's former veep, Mike Pence, who supports a 15-week federal ban on abortion, took umbrage with this. “Nikki, you're my friend, but consensus is the opposite of leadership,” Pence scolded. (As the Never Trump conservative writer Jonah Goldberg has pointed out on his podcast, building consensus is often a key attribute of leadership.)The Republican Debate Was a Futile Pudding Wrestling MatchThis exchange, like others during that same debate, made it clear that in a general election Nikki Haley would likely be Joe Biden's most challenging opponent.Having served as governor of South Carolina and ambassador to the United Nations, she has the experience needed for the office. She also has sharp elbows. (“You have no foreign policy experience and it shows,” she told Vivek Ramaswamy.)At 51, Haley would present a stark contrast in terms of generational change, assuming that Joe Biden was still the Democratic nominee. And (unlike others) she is not staking out an abortion position that might render her effectively unelectable, should she become the Republican nominee.Haley (who frequently cites Margaret Thatcher's line, “If you want something said, ask a man. If you want something done, ask a woman”) was the only woman on that stage. Her identity, temperament, and policy positions could help chip away at the gender gap that has only grown in recent years.The obvious caveat here is that all of these things would make Haley a great candidate to beat Joe Biden if she somehow wins the Republican nomination. But that's an awfully big “if.”Kareem Abdul-Jabbar: GOP Debate Showed How Not to Pick a PresidentHaley's answer to this is to make the electability argument: “We have to face the fact that Trump is the most disliked politician in America,” she—and she, alone—averred during last week's debate.But will that dog hunt?Right now, the electability argument isn't persuading Republicans to jump off the Trump bandwagon, even though that argument is likely the only one that could ever work. At some point (perhaps after Donald Trump goes on trial and it's too late), Republicans might be convinced that, as entertaining as Trump is, he simply can't win.Based on all of this, you might expect me to suggest that it's time to clear the field—to rally every freedom conservative, Reagan Republican, and Never Trump conservative to coalesce around Haley as the GOP's last, best hope.Some of my colleagues are already there. The New York Times columnist David Brooks, for example, declared last week that “Wednesday's debate persuaded me that the best Trump alternative is not [Tim] Scott, it's Nikki Haley.”But here's my problem. Haley has been all over the map for years now. One day she's courageous and impressive, and the next day she's a pathetic Trump toady.Haley is a political chameleon, which makes me reluctant to ever trust her again.Trump and Ramaswamy Show Us How the Worst Get to the TopOn the other hand, anyone looking for purity (as it pertains to Trump) can also dismiss Pence and Chris Christie—both of whom supported Trump until Jan. 6—and a vast swath of today's leading Never Trumpers. As the Good Book says, “Who then can be saved?”Nikki Haley's got a long way to go before she clears the not-Trump lane of candidates, much less taking on the final boss himself. And though nothing has yet made a dent in Trump's domination of the GOP voter base, he's never run as a candidate on trial before. But the whole 91-felony indictment thing might just do the trick.If Haley can prove herself by stringing together two or three of these kinds of courageous performances—in which she not only characterizes Trump as the guy who already lost to Biden, but also that she's as real a conservative as any of the other contenders—there is a path to success.It's hardly guaranteed, and as I've noted, courage comes and goes with Haley. But in the “Matt Lewis primary,” you can count me among the 46 percent who are now considering voting for her.Read more at The Daily Beast.SEMAFOR: Nikki Haley's abortion message could catch on in the GOPMorgan Chalfant and Kadia GobaRepublicans worried about Democrats leveraging abortion (again) to make gains in 2024 want GOP candidates to take a page out of Nikki Haley's debate prep playbook.Haley dismissed the idea that a 15-week national abortion ban could pass through Congress. Instead, she argued the focus should be on finding “consensus” around banning “late-term abortions,” sustaining access to contraception, allowing doctors who don't support abortion refuse to perform them, and preventing women who get abortions from being penalized.Defeated Michigan gubernatorial candidate Tudor Dixon bluntly said on Fox News that Republicans would lose the messaging war in 2024 unless they followed Haley's “perfect response” in the debate.“No one really understood how important abortion would be in 2022 because no one had run in a post-Roe world, so we suddenly got attacked, viciously attacked, by the Democrats, and it is a winning message for them,” she said. Gov. Gretchen Whitmer highlighted Dixon's opposition to rape exceptions in abortion bans in their contest, which took place alongide a ballot initiative guaranteeing abortion rights that passed by a wide margin.“The only candidate on the stage that talked about how we should protect women and not demonize them was Nikki Haley,” Rep. Nancy Mace, R-S.C. said Sunday on CBS of the first GOP presidential debate. “And that is a message that we have to carry through. We have to be pro-woman and pro-life. You cannot go after women and attack them because they make a choice that you don't like or don't agree with.”And Rep. George Santos, R-N.Y., who represents a district President Biden won in 2020, told Semafor at a watch party last week: “She had probably the best-packaged message on abortion that I've heard, I want to say, in my entire adult life.”Haley might have won herself some fans, but her position wasn't a favorite within the anti-abortion movement, which has rallied around a 15-week federal ban as a minimum ask for candidates.

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David Epstein joined Seagen as Chief Executive Officer and a member of the Board of Directors in 2022, bringing more than 30 years of drug development, deal making, commercialization and people leadership experience on a global scale. Prior to Seagen, he was executive partner at Flagship Pioneering. From 2010 to mid-2016 he served as Chief Executive Officer of Novartis Pharmaceuticals, a division of Novartis AG.Previously, David started and led Novartis' Oncology and Molecular Diagnostic units. Over the course of his career, he led the development and commercialization of over 30 new molecular entities, including major breakthroughs such as Glivec, Tasigna, Gilenya, Cosentyx and Entresto.David holds a B.S. Degree in Pharmacy from Rutgers University College of Pharmacy and an MBA in Finance and Marketing from the Columbia University Graduate School of Business. He serves as a member of the board of directors for OPY Acquisition Corp. I and Senti Biosciences, Inc.w/ Special Guest Host: Brian Fiske - Co-Founder & CSO @ Mythic TherapeuticsBrian Fiske co-founded Mythic in 2017 & currently serves as Mythic's Chief Scientific Officer. Prior to Mythic, he was a co-founder and Chief Technology Officer at Ohana Biosciences and a Senior Associate at Flagship Ventures, where he also co-founded KSQ Therapeutics. During his time at Flagship, Brian successfully led R&D teams to key milestones, recruited 25+ FTEs across all levels of seniority, and raised $34M across multiple rounds of financing. In 2016, he was nationally recognized for healthcare entrepreneurship by Forbes 30 under 30.Prior to Flagship, Brian completed his PhD in biology in Matt Vander Heiden's lab at MIT where he published over 10 papers in the field of cancer metabolism. He also worked closely with Agios Pharmaceuticals (NASDAQ: AGIO) on their cancer metabolism programs, which have since translated into four clinical programs that include two approved drugs. He holds an AB summa cum laude in Biochemical Sciences with a secondary field in Economics from Harvard University.Alix Ventures, by way of BIOS Community, is providing this content for general information purposes only. Reference to any specific product or entity does not constitute an endorsement nor recommendation by Alix Ventures, BIOS Community, or its affiliates. The views & opinions expressed by guests are their own & their appearance on the program does not imply an endorsement of them nor any entity they represent. Views & opinions expressed by Alix Ventures employees are those of the employees & do not necessarily reflect the view of Alix Ventures, BIOS Community, affiliates, nor its content sponsors.Thank you for listening!BIOS (@BIOS_Community) unites a community of Life Science innovators dedicated to driving patient impact. Alix Ventures (@AlixVentures) is a San Francisco based venture capital firm supporting early stage Life Science startups engineering biology to create radical advances in human health.Music: Danger Storm by Kevin MacLeod (link & license)

Join Tina Fascetti, CCO of The Agency Network at MJH Life Sciences for a podcast interview with Ryan Potter, ACD Art, and Priscila Ramos, ACD Copy, from McCann Health as they share the "behind the creative" story of their Apex Award-winning consumer creative campaign for Entresto. The Apex Awards is judged by none other than the people they are aimed to connect with, the patients themselves.

****DISCLAIMERS: THESE PRICE COMPARISONS ARE NOT PROMOTIONAL. THE MANUFACTURERS WERE NOT INVOLVED IN THE MAKING OF THIS PODCAST MINISERIES. THESE WERE REQUESTS FROM PODCAST LISTENERS ON DRUG PRICING EXAMPLES ONLY - TO BE USED FOR EDUCATIONAL PURPOSES ONLY AND NOT PROMOTIONAL IN NATURE. NOTE AS WELL THAT ANY OPINIONS EXPRESSED BELOW ARE BY PODCAST HOST AND PHARMACIST, DR. ERIN ALBERT, AND NOT NECESSARILY THOSE OF ANY OF HER EMPLOYERS OR AFFILIATIONS. PRICES AND OFFERS CAN CHANGE AT ANYTIME WITHOUT NOTICE.**** Entresto (Sacubitril / Valsartan) is our first drug to hunt for the best price - you'll want to go over to our resource guide, request a copy and then look at the "Entresto" pricing tab. Our resource guide tracker, which you can request access to here. --- Support this podcast: https://anchor.fm/theedutainer/support

In this episode, we review new updates and key concepts from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. This guideline is newly published (April 2022) and is a full update of the 2013 guidelines and the 2017 focused update for heart failure. Key Concepts Heart failure is classified as HFrEF (heart failure with reduced ejection fraction = 50% with increased LV filling pressures). Most drug therapy recommendations are similar for HFrEF, HFimpEF, and HFmrEF whereas HFpEF therapies are different. The 2022 AHA/ACC/HFSA heart failure guidelines now recommend SGLT2 inhibitors, such as dapagliflozin and empagliflozin, in patients with HFrEF, HFmrEF, and HFpEF. The 2022 AHA/ACC/HFSA heart failure guidelines continue to prefer ARNi, such as sacubitril/valsartan (Entresto), over ACE inhibitors and ARBs in patients with HFrEF. Based on the PARAGON-HF trial, ARNi is also recommended in those with HFpEF albeit with a weak recommendation. Avoiding excessive dietary sodium is reasonable to reduce congestive symptoms in patients with heart failure; however, guidelines do not recommend a specific maximum intake nor does data support clinical outcome benefit with dietary sodium restriction. References Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published online ahead of print, 2022 Apr 1]. Circulation. 2022;101161CIR0000000000001063. doi:10.1161/CIR.0000000000001063. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063 Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399(10333):1391-1400. doi:10.1016/S0140-6736(22)00369-5

Why is hibernation something that bears and squirrels do, but humans don't? Even more interesting, what's going on inside a hibernating animal, on a physiological and genetic level, that allows them to survive the winter in a near-comatose state without freezing to death and without ingesting any food or water? And what can we learn about that process that might inform human medicine?Those are the big questions being investigated right now by a four-year-old startup in California called Fauna Bio. And Harry's guests today are two of Fauna Bio's three founding scientists: Ashley Zehnder and Linda Goodman. They explain how they got interested in hibernation as a possible model for how humans could protect themselves from disease, and how progress in comparative genomics over the last few years has made it possible to start to answer that question at the level of gene and protein interactions. The work is shedding light on a previously neglected area of animal behavior that could yield new insights for treating everything from neurodegenerative diseases to cancer.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.It's April and spring is well underway, even though it's been a pretty cold one so far here in New England.It's the kind of weather that makes you want to pull the covers over your head in the morning and just sleep in. Or maybe just hibernate like a bear until summer is really here.But when you think about it, what is hibernation? Why is it something that bears and squirrels do, but humans don't?Even more interesting, what's going on inside a hibernating animal, physiologically, that allows them to survive all winter without freezing to death and without ingesting any food or water?And what can we learn about that process that might inform human medicine?Those are the big questions being investigated right now by a four-year-old startup in California called Fauna BioAnd my guests today are two of Fauna Bio's three founding scientists: Ashley Zehnder and Linda Goodman. I asked them to explain how they got interested in hibernation as a possible model for how humans could protect themselves from disease.…And how progress in comparative genomics over the last few years has made it possible to start to answer that question at the level of gene and protein interactions.We've always looked to the natural world, especially the world of plants, for insights into biochemistry that could inspire new drugs. But what's exciting to me about Fauna Bio is that they're shining a light on a previously neglected area of animal behavior that could yield new insights for treating everything from neurodegenerative diseases to cancer.So, here's my conversation with Ashley Zehnder and Linda Goodman.Harry Glorikian: Ashley. Linda, welcome to the show.Ashley Zehnder: Thanks, Harry, we're excited to be here today. It's going to be fun.Linda Goodman: Yeah, thanks for having us.Harry Glorikian: Yeah, I mean, well, you guys are someplace sunny and warm, and I'm actually I shouldn't say that it's actually sunny right now on the East Coast. So I'm not I'm not.Linda Goodman: Don't jinx yourself.Harry Glorikian: But the temperature is going to drop. Like to I think they said 18. So everything will freeze tonight for sure. So it'll, you know, it's one of those days, but. I want to jump right into this because we've got a lot of ground to cover. Like there's so many questions that I have after sort of looking into the company and sort of digging in and, you know, but even before we jump into what you're working on. Right, I really want to talk about hibernation. Maybe because I'm jealous and I'd like to be able to hibernate. I have sleep apnea. So sleep is a problem. But humans don't hibernate. But there's a ton of other mammalian species that that do. And sometimes I do feel, though, that my teenager hibernates, but that's a different issue. So, but, what what is interesting to you about hibernation from a physiological point of view. What what goes on with metabolism or gene expression during hibernation, that's that's not found in humans, but that could be relevant to human health?Ashley Zehnder: Yeah, I think this is a great question, Harry, because I think both Linda and I came to fauna from different backgrounds. I came from veterinary science, Linda from comparative genomics. We can go into our details later, but neither of us really appreciated the amazing physiology of these species. There are some of the most extreme mammals on the planet, and there are hibernating bears and literally every group of mammals. Right. This is something Linda specializes in. But there are primates in Madagascar that hibernate very similar to the 39 ground squirrels that we tend to work with. So it's this really deeply conserved trait in mammals, including primates. And, you know, it kind of highlights for us what our genes can do when they're adapted for extreme environments. And so that's kind of the lens that we take when we look at hibernation. It's how do these species protect their own tissues from being nearly frozen for six, seven months out of the year, having to protect their brains, their hearts, all their vital organs? They're not eating, they're not drinking. They're not moving for these really deep bodied hibernaters. When you think of 100 kilogram animal that's not eating for seven months, how do they survive that? Right. And it has to do with metabolic rates that change 200- to 300-fold over the course of a couple of hours. It has to do with oxygenation changes and protection from oxidative stress and ischemia reperfusion. And so if you look at a tissue by tissue level, you can start to see how these animals are finally adapted to protecting themselves from from damage. And then we can start to say, well, this is similar damage to what we see in human diseases. And that's why this is such an interesting system, because it's so dynamic and because it happens across so many groups of mammals, it really lends itself to this comparative genomics approach that we take to drug discovery.Harry Glorikian: Yeah. Because I was wondering sort of like what ways of healing from different sort of traumas and conditions do hibernating animals have that that humans don't, that we sort of maybe wish we did? It's sort of like, you know, almost Marvel or one of those things where you like go to sleep, you wake up, you've totally healed again, which kind of be kind of be cool. Yeah. So, you know. But when did scientists first begin to think about whether having a better understanding of hibernation might help us solve? Some of these riddles that we have in human health. I mean, it surely it can't be like a new concept. It has to go further back. I mean, what has changed recently to make it more actionable? I mean, is it, you know, omics, costs coming down that are making it easier, computational capabilities that are, you know, making all these come together? I mean, those. What do you guys. What's. What's the answer? You guys know the answer better than I do.Ashley Zehnder: I'll comment on a little bit on the physiology, and I will let Linda talk about the data revolution, because that's that's really what she knows very intimately. So from a physiology standpoint, these are species and not just hibernaters, but a lot of other species that we've been studying since the early 1900s, 1950s. I mean, these are some of our earliest biological experiments and our earliest understandings of biology. We're not necessarily done by studying humans. A lot of that was done by studying natural disease models, right? How did we figure out that genes cause cancer? So it's a little bit of a tangent, but bear with me, it was not by studying human cancer, it was by studying Rous Sarcoma Virus and how that virus picked up bird genes and then turn them on. Right and other in other individuals. So but then kind of this almost the same year in 1976 that we figured out that genes cause cancer by studying chickens. 1974 we figured out how to genetically modified mice. And we sort of figured out that like, okay, maybe we don't need to study natural biology anymore. And so I feel like we sort of lost a lot of those skills and figured out we had humans and we had model organisms and we were done. And I think now we're kind of in this renaissance where people are realizing that actually there's still a lot of natural biology that we can learn from. But it's being powered now by this data revolution and the decrease in cost and sequencing and availability of omics data like RNA. Seq and then I will pitch that over to Linda because that's really what she knows best.Linda Goodman: Yeah, yes, absolutely. You know, Ashley's right. And I think just to add on to that, that there was this issue in which there were a lot of field biologists out there working with these really fascinating hibernating animals. They knew a lot about what these animals could do, the extreme environments they were exposed to, that they could overcome, they could protect all of their tissues. And there was so there was a group of field biologists who knew all that information. And then on the other side, you have all of these geneticists who are studying the genomes of probably humans and mouse and rat. And they weren't really talking to each other for a long time. And I've been in the genomics field for at least a decade, and not until very recently did I even hear about all these amazing adaptations that these hibernating mammals have. So I think some of it was just a big communication gap. And now that the genomics field is starting to become a little more aware that all these exciting adaptations are out there that we can learn from, I think that's going to be huge. And yes, of course, it certainly does not hurt that there's been a dramatic drop in sequencing costs. We can now sequence a reference genome for around $10,000. That was unheard of years ago. And so a lot of these species that people would previously consider untouchables because they were not model organisms with a pristine reference genome, we can now start to approach these and thoroughly study their biology and genomics in a way that was not possible several years ago.Harry Glorikian: Yeah. I was thinking I was, you know, I was laughing when you said $10,000, because I remember when we did the genome at Applied Biosystems and it was not $10,000.Ashley Zehnder: Yeah.Harry Glorikian: Yeah. And it took I remember Celera, we had an entire floor of sequencers working 24/7 I mean, it was an amazing sight. And now we can do all that, you know, on a.Ashley Zehnder: Benchtop. Benchtop. Exactly. On a benchtop.Harry Glorikian: So. But, you know, it's interesting, like in a way, studying animals to learn more about disease mechanisms seems like a no brainer. I mean, we share a, what, about 99% of our DNA with chimpanzees. And for those listening. Yes, we do. You know, I'm sure there's people out there that, like, bristle when I say that. But what is it, 97.5% of our DNA with rats and mice. That's why we use all these things for sort of safety and effectiveness of drugs meant for humans. But. Still, I'm not used to drug hunters starting out by looking at animals, you know? Why do you think it's taken the drug industry, although I'm I say that very loosely, [so long] to wake up to that idea?Ashley Zehnder: Yeah. I think it's I think it's again, this almost reversal of the paradigm that exists today, which is let's take a human disease that we want to make a new drug for. Let's take a mouse and let's try to genetically manipulate that mouse to mimic as closely as possible what we see in the human disease. And those are always imperfect. I mean, I did a cancer biology PhD at Stanford, and there's that trope of like, Oh, if I had a dollar for every time you occurred mouse in a human right, it would need to work anymore. That's replicated across many fields, right? They're not good models. And so we're saying like obviously that doesn't really work for discovery. It's fine for preclinical and safety and you have to use those models. But for pure discovery, that's not where you want to be, right? Instead, you want to take the approach of saying, where has nature created a path for you? Where is it already solved this problem? And I think there are companies like Varian Bio who are doing this in human populations. We're saying, let's look at humans that have unique physiologies and a unique disease adaptations. And of course then you have to find those niche pockets of human populations.Ashley Zehnder: So that's not a not a simple problem either. But the approach is very analogous. What we're saying is we can use that rare disease discovery approach and just expand that scope of discovery. Look at highly conserved genes, look at how other species are using them to reverse how phosphorylation in the brain to repair their hearts after damage, to reverse insulin dependence. To heal, we'll heal their tissues or regenerate stem cells. Let's just see how nature did it right and just mimic that instead of trying to fix something that we artificially created. So it's literally reversing that paradigm of how we think about animals and drug discovery. But you have to know how to do that. You have to know which models are correct. You have to know how to analyze 415 genomes together in an alignment which is really complicated. Linda knows how to do that, so you have to know how to do it correctly, although you could screw it up very badly. So there's a lot of expertise that goes into these analyses and also again, the data availability, which wasn't there nearly a decade ago. So.Harry Glorikian: So I asked this question out of pure naivete, because I'm not sure that I could sort of draw a straight line. But, you know, which drugs were have been discovered through research on genetic mechanisms of disease in animals. Is there, are there?Ashley Zehnder: You know, I think directly it's a new field. Right. So I think, Linda, you and I have looked at some examples of looking at drugs for narcolepsy, looking at dog genetics and studies, looking at muscle disorders in certain species of cattle that have naturally beefed up muscles and translating those into therapies. I mean, there are examples of looking at animals for things like genotype, right, came from Gila monster venom, although that's not strictly a genetic program. Right? So I think this idea of looking at natural animal models is a source of innovation. It's just that, again, the data wasn't really available until fairly recently, but we know the strategy works by what's been done on things like PCSK9 inhibitors in humans, right? It's a very similar approach to that. It's just expanding that scope of discovery.Harry Glorikian: So because you guys raised money and you guys are moving this forward, sort of and I don't want you to tell me anything that's confidential, but. So what was the pitch when you when you put that in front of everybody?Ashley Zehnder: It was really that, look, drug discovery right now is really been hampered by a lack of innovation. And we're really stuck in looking at these very kind of currently limited data sources, which is humans and again, these handful of really imperfect animal models. But we can take what we've learned from working with human genomics and really greatly expand the opportunities for a number of diseases that still don't have good therapies. Right. We've had the human genome for really close to 20 years now. We spent a lot of money sequencing it. And still, if you go back and look at the FDA approvals in the last two years, which I did by hand a while ago, or more than three quarters of those are not new targets. They're new drugs for a new indication or new drugs, same drugs before a new indication or they're kind of meta pathway drugs or they're drugs for which we still don't know the mechanism. It's some small molecule. It's been around since fifties. And so like where is the innovation in the top ten diseases of people still have it changed? So like where I pulled these two headlines right not too long ago, one from 2003, which is like the era of the genomics revolution. Right? And then one from 2019, which was the genomics revolution question mark. Right. Like we're still sort of waiting for it. And so what is that missing piece of data that's really going to allow us to really leverage the power that's in the human genome? And to do that, we have to put our own genes in an evolutionary context to understand what's important. That's been that third dimension of genomics that's been missing. So it's really not necessarily about any particular species that we work on, all of which are amazing. It's really about using that data to shine a better light on what's important in our own genome. And so that's a lot of the pitches, like how are we going to use our own genome better and find better treatments?Harry Glorikian: Yep. Understood. So. You have a third founder, Katie Grabek. Right. So. Tell me about yourselves. I mean, did the three of you get interested in comparative genomics and hibernation? How did you come together? How did you decide like, oh, hey, let's do a startup and get this thing going in this area? So tell tell me the origin story.Ashley Zehnder: Linda, do you want to kick off?Linda Goodman: Sure. I think it all really started, Ashley and I initially started batting a few ideas around. We both had this understanding that that drug discovery today did not look outside of human mouse rat very much. And we both understood there was this wealth of animal data that's just waiting to be used and no one was doing it and we couldn't really figure out why. And we were having trouble figuring out exactly which animal we wanted to study and which diseases we wanted to study. And it just so happened that we lucked out. There was another woman in our lab at Stanford, Grabek, who had the perfect study system for what we were thinking about. She had these amazing hibernates our animals that have exquisite abilities in terms of disease, resistance and repair. And once she started talking about all the amazing phenotypes these animals have, we thought, wow, that would make a great study system to make the next human therapeutic. Yeah. And I think it's interesting that both Katie and Linda have human genetics PhDs. Right. So I think both of them and Linda can expound on this. But from Katie perspective. Right, she she went in to do a human genetics Ph.D. trying to understand how genes can be used to improve human health and shouldn't be rotating the lab of somebody who studied the 39 ground squirrel and said this physiology is way more extreme than anything we see in humans, but they're doing it using the same genes.Linda Goodman: What are those genes doing in these animals that we can adapt for human therapeutics? And so she brought that work with her to Stanford and was really one of the preeminent researchers studying the genetics and genomics of these species. My background is I'm of Marion, so my clinical training is in exotic species. So as a clinician, I treated birds, mammals, reptiles and saw that they all presented with different kinds of diseases or in some cases didn't present with diseases like cancer that were super interesting. And then coming to a place like Stanford to do a PhD, it was working with a bunch of human researchers, human focused researchers. They're all generally human researchers, but you know what I mean? It's a little bit tricky with the nomenclature. Generally, I have my doubts about, you know, maybe there's some chimpanzees doing research somewhere, people studying human diseases, right from a human lens who are completely ignorant of the fact that animals often also had these disease traits or in some cases were resistant to them. So there was this huge disconnect there of of biologists and veterinarians and physiologists who understood all these traits across different species and the people who knew the molecular mechanisms, even though a lot of those are shared.Linda Goodman: And so one of the things that I found really interesting just from a cancer perspective was that a lot of our major oncogenes are highly conserved because these are core biological genes that if you screw them up, will give you cancer. But there's an evolutionary pressure to maintain these genes. And so there's a reason why they're conservative, because they're really important biologically, and that's true across many other diseases as well. So from that perspective, I was really interested in this intersection of human and animal health. I always wanted to do more genomics myself and just never had had the training. Linda had always been interested in veterinary science, and so we kind of immediately started collaborating and saying, Look, look, there's a huge opportunity in this, again, third space, third dimension of genomics that people are not looking at. What do we do trying to start a comparative genomics company? I'm using air quotes here for the podcast listeners is a little bit broad. Where do you start? And I think Katie really gave us that start in saying, here's a model. We have a biobank of samples that are proprietary to fauna. We have an expert in this field. We have a model that's good for so many different diseases. Let's prove that the process works here and then we can expand into multiple disease areas.Harry Glorikian: You know, you got to love, people I think, underestimate that magic that happens when the right people get together and the spark happens, right? I mean, I'll take that. Any day. I mean, I love coming up with a plan and then, you know, working to the plan. But when it happens, when the right people in the room and they're all get excited, those are those are the most incredible start ups, in my opinion. Yeah. So you're starting off with targets in heart disease, stroke, Alzheimer's, diabetes, very different areas, right? Cardiovascular, neurodegenerative and metabolic. So. Why start with those areas in particular?Linda Goodman: So I think for us it was really again showing showing what we can translate from this model. So some of the phenotypes that we see, the traits that we see in the ground squirrel, which is predominantly one of the species we use for our work, is that they're exquisitely resistant to ischemia, reperfusion injury. So the kind of injury that gets, if you have a heart attack and you go and get the heart attack on block, you get this rush of warm, oxygenated blood back into your heart that can actually be damaging. And that's a lot of what causes damage after a heart attack, what these animals happen, they do this 25 times over the course of a 6 to 7 month hibernation cycle. And if you look at their hearts in the peak of one of these periods, there is an upregulation of collagen, which is cause of fibrosis. There's an upregulation, there's histologically, there's a little bit of damage. It's less than you would I would have, but there's a little bit there. But if you get to the end of that whole cycle and look at their hearts, they look normal and they do it again next year. Right. So you and I could not survive 25 of these attacks over six or seven month period, right? Obviously not. So let's pick the strongest phenotypes we have in these animals and let's show that we can use information from that and come up with genes and compounds that are protective in our more standard models of these diseases.Linda Goodman: And that's what we did really with the first round of data that we had is we generated four genetic targets and two compounds that came out of the heart data that we had from hibernating and that we tested them in human cardiomyocytes in a dish and said if we take oxygen and glucose away from these cells, they get really unhappy and die and we could double survival of human heart cells in a dish. And then we said, okay, great, let's actually move this into animals. And so we used AAV or some of these viral vectors to then knock down genes in vivo in hearts of rats. So we literally tied off a coronary artery and then let the blood come back in and saw that we could almost fully protect these hearts from damage by knocking down genes that we found in the hibernating data. So it was really closing that loop and saying, where are the strongest traits? Can we show that this works? And then it was really figuring out where are the really large areas of unmet need. And so in terms of metabolism, we end up connecting with Novo Nordisk, which is a publicly disclosed partnership. They are very focused on obesity. We have a model that increases this metabolism, 235 fold over an hour. Name another model that can do that, right?Harry Glorikian: I need that. I need that. I need like, because...Ashley Zehnder: We all need that!Harry Glorikian: I could get rid of a few pounds right around here.Linda Goodman: Exactly. So then it's really just figuring out where are the unmet needs, who is really interested in these areas we're looking at and do we have unique data that speaks to those models? And that's really we just try to be guided by the biology and saying, where do we have unique data sets that can answer high unmet needs?Harry Glorikian: Okay. Well, all I mean, all sounds super exciting if we can make the translation, you know, in the right way and find those targets. But. You guys have built up a significant biobank, right? I understand you have a huge database of genomic readout from various hibernating animals. Can you tell us a little more about the extent of that biobank? How did you collect the data and how unique is that database in the industry?Ashley Zehnder: Yeah. Linda, do you want to talk a little bit about the data sources that we're currently using at Fauna?Linda Goodman: Yeah. So maybe, you might be the best person to talk about the Biobank and then I can talk about all the other data sources layering on top of that.Ashley Zehnder: Yeah, I'll talk a little about the BiobanK. So we have yeah, we have a number of different data sources. The Biobank is one of them and probably one of the main ones that we use. So Katie, during her PhD, built a really unique biobank of very precisely time tissue samples from 39 ground squirrels across the whole hibernation cycle. And the reason why that timing is so important is because the cycle is so dynamic. If you don't have really precise sample timing, you end up with a big kind of smush of data that you can't tease apart by having really precisely timed data points, you can separate these genes into clusters and know exactly kind of where you are in time. And that timing relates to the physiological injuries that we study. So we know what time points their hearts are protected because those physiological studies have been done. We've looked at those time points very specifically. So we have that biobank of samples that we in licensed as founding IP at Fauna CANI literally drove it across the country in a U-Haul because we didn't trust anybody to move it. So that's that's now in our freezers and Emeryville with a cadre of backup batteries to protect it.Ashley Zehnder: So that's the founding data that we have. And that's been really crucial because I look at other companies trying to use data for drug discovery, particularly in the early stage. A lot of it is kind of publicly available data or cell lines or kind of shared data sources. And part of what is unique about font, as we literally have truly novel data sources that we're starting with that are wholly owned that we control and we know the quality of those. So that's really the Biobank that we have is and it's 22 different tissues. I mean, it's brain, it's kidney, it's lung, it's hard. It's liver or skeletal muscle. Right? Pretty much every kind of tissue you would want in that founding biobank. But then on top of that, I think what we've done with the other data is super important. Yeah. And so we layer on top of that all sorts of publicly available data and also data we've been able to source, such as human data from the UK Biobank. But I really want to hit on the point of, of why the model species hibernate or data is so different. All of the other data that most people work with is trying to compare animals that are healthy to animals that are diseased, or people that are healthy to people who are have disease. What's really unique about the model species that we're working with is we're trying to figure out why they have these superpowers in terms of disease, resistance and repair.Ashley Zehnder: So it's kind of the other end of the spectrum that we're making this comparison between a normal, normal hibernate or during, say, the summer months and then a hibernate or that has gene expression patterns that mean that it's resistant to many diseases and it can repair tissues when it gets damaged. So it's actually quite different from the normal types of comparisons that others would make. But yes, and then we integrate publicly available data from sources like Open Targets Reactance. And one of the other data sets that we work with that's that's valuable is that we go back through literature that is relevant to the disease, indications that we're going after. And we have a team of curators that mines these papers that where the biology is relevant and we integrate those transcriptomic studies generally into our database. And that that really helps with our comparisons. And I can kind of give you an example of the way that we would do this type of cross-species analysis compared to what other what others in the industry might do if they were just looking at humans or say, just looking at mouse and rat is that, you know, if you're if you're just looking at at a human study and you're trying to say, look, for what genes do we think are involved in heart failure? You would look at, say, transcriptomic, differences between healthy human hearts and failing human hearts.Ashley Zehnder: And then you would have some type of gene list where you'd see the genes that have differential regulation between those two groups. And it fa not we we look at that type of data and then we also look at hibernate or data and then we can compare that. And that's really where the magic happens because we can look at hibernate hours when their hearts are protected during the winter months. So we have an example of these are genes that are involved in protection and then compare that to the summer months where they're not protected. And then we can integrate both of those to analyses so we can say what's really different about a human heart when it is failing to a hibernating heart when it is protected. And we do very fancy types of network analyses and then we layer on all of these data from external sources and the really exciting moments where we see these networks light up with the exact regulation patterns we are expecting that is relevant to our biology. Those are really fun. And I would say the other data source, Linda, that would be good to touch on is the genomic data, right? I think the comparative genomics data. So maybe give a little context on that. I think that really broadens the the views point of what we work with.Linda Goodman: Yeah, absolutely. So that's another data source that we work with. We have a collaboration with the Broad Institute that is one of the leaders of the Zoonomia Project that has in the neighborhood of 250 mammals in a in a big alignment. So we can do comparative genomics across all of these animals. And what we like to look for are comparing the genomes of animals that have a specific phenotype to others that don't. So for example, what is different in the genomes of hibernaters compared to the mammals that cannot hibernate? And we typically do this with how fast or slow evolving genes are, right? So if a gene doesn't accumulate very many mutations in hibernate hours, then it's probably pretty important for hibernation because there's a lot of purifying selection on that versus say, in other mammals that are not hibernaters, like like a human or a rat. It got a lot of mutations in it because it didn't matter as much for those animals. So that's another way of pinpointing the genes that are really important to hibernation. And we know, of course, that some of those might relate to the overall hibernation trait, but many of them are going to be disease relevant because they've had to evolve these genes in a way to protect their hearts and their other organs from these extreme environments they're in during hibernation.Harry Glorikian: So that, if I'm not mistaken, so did the Zoonomia Consortium, there was a big white paper about comparative genomics published in Nature.Ashley Zehnder: Nature last year? Yep. Two years ago. Yeah. A little bit.Harry Glorikian: Yes. Time seems to blur under COVID.Ashley Zehnder: Yeah.Harry Glorikian: How long have I been in this room? Wait. No.Harry Glorikian: But. Can you guys I mean, because doing comparative genomics is not, you know. It's not new necessarily, but can you guys summarize sort of the. Arguments or the principles of that paper, you know, quickly. And then, you know, my next question is going to be like, do you feel that Fauna Bio is part of a larger movement in science and drug discovery that sort of gaining momentum? So I'll, I'll I'll let you guys riff on that launch.Ashley Zehnder: Linda, you're you're the best one to do a perspective on that paper for sure.Linda Goodman: Sure. Yeah. You know, I think this is really born out of the concept that in order to identify the most important genes in the human genome, we need to be looking at other animals and more precisely, other mammals to see their pattern of evolution. Because if you see a gene that looks nearly identical across all other mammals, that means that it's really important. It means that it has been evolving for somewhere in the neighborhood of 100 million years, not accumulating mutations, which really translates to if you got damaging mutations in that gene, you were a dead mammal. Those have been selected out. And that's really how you can tell these are the key genes that are important to to your physiology, the difference between life and death. And you can't understand those things as well by just looking within humans and human populations. We're all too similar to each other. But it's really when you get to these long time scales that the statistics work out where you can see, okay, this has been this mutation has not happened in 100 million years. We don't see it in anybody's genome. So that is obviously very important. And that's just this other way of looking at our own human genome that helps highlight the genes that are going to be important to diseases. And I think, you know, another side to this paper related to conservation and the fact that a lot of these animals with really exciting genomes, the ones that are exciting to people like us, are those that have these really long branch lengths where they're they're kind of an ancient lineage. And that's really where the gold is, because that helps us even more understand how quickly or slowly some of these genes are evolving, and it related to trying to conserve some of these species as well.[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: I should say congratulations because you guys did raise a $9 million seed round last fall from a group of venture funds, some in life sciences, some more general. Right. What does that funding do? What is it? What does that unlock next?Ashley Zehnder: You. I will answer that question. I do want to jump back to your other question that was kind of is this part of a larger movement and comparative genomics? Right. I think that's an important question. I think you sort of hit the nail on the head there. We were invited to a symposium in August of 2019 called Perspective and Comparative Genomics that was held at NHGRI in Bethesda. And I think there's a recognition and actually some of our grant funding is also through NHGRI. And I think there's a recognition from the folks who sequenced the human genome, that they don't have all those answers. And so it's an interesting time where we realize that there is this kind of other data out there that can help us really understand that better. And it does feel a little bit like a rising tide. And so that's that's something that I think is important to recognize. But in terms of the seed round, really, that was meant to expand the platform and the pipeline that we built with our initial funding back from Laura Deming and Age One and True Ventures, who led around for us in early 2019. It's really saying like that initial $3 million or so is really to say like, does this work or is this crazy, right? Can we it's just a crazy idea.Ashley Zehnder: And that's what we really started to generate those first few animal studies that said, yes, actually we can find genes and compounds from this data that meaningfully affect not only human cells, but animal models of human disease. And now we're really expanding into new disease areas. We're looking at areas like fibrosis. We're looking at areas like pulmonary disease. We've got some really interesting data coming out of animal models of pulmonary hypertension with a compound that we found on our platform. We've got the collaboration with Novo Nordisk, which of the five genes that they tested in animals? We have one that has a significant obesity phenotype. So I mean, 20% hit rate on a novel target discovery in vivo is not bad, right? So we've gotten to the point now where repeatedly over multiple disease areas, we've seen that between 20 and 30% of our either compounds or genes are hits, which shows us that this is not only kind of a we got lucky in cardiac disease, but actually this is a process for enriching for important drug targets. And now it's a matter of really expanding the pipeline. We brought on a really experienced head of Therapeutics Discovery, Brian Burke, who spent 20 years at NIBR running very early discovery programs and then seeing programs go into the clinic.Ashley Zehnder: He worked on drugs like Entresto and then worked on a couple of startups after that. So he's kind of gotten both big pharma and startup experience, and his job at Fauna is to really look at the menu of things that we're presenting him from an early research and discovery phase and picking the winners and really figuring out how to take them forward and also killing the programs that are less exciting to him for a number of technical or practical reasons. So that's been really, really helpful to have someone come in truly from the outside and take a look at the science at Fauna and say this is as good or better as anything that I've worked on before. I'm really excited to work on this, and that's been kind of a nice external perspective on on the science and the pipeline at Fauna. So that's really what the $9 million is for. It's really expanding a lot of the computational expertise and and progress and Linda can talk a little bit about that, but also just expanding into new disease areas as well.Harry Glorikian: Understood. So, you know, on this show, like, I talk a lot about, you know, technology, data, and how it's all affecting health care, which this all fits into. But one of the things we talk about a lot is how crappy, terrible, I should use, you know, terrible, right, electronic health records are in the lack of interoperability between them. And Ashley, you actually wrote a paper.Ashley Zehnder: I did, yeah, veterinary medical records are just as bad, actually, veterinary medical records are probably a little bit worse, if it's possible.Harry Glorikian: And to be quite honest, I'm sorry, I just hadn't thought about Fifi or Rover and their...Ashley Zehnder: Their medical records.Harry Glorikian: EHR. Is like is the problem bigger, even, when it comes to functional genomics? I'm trying to think of like obtaining and storing and analyzing 'omics of different species. I mean, who's working on this? Is that part of the Zoonomia consortium? Right. I'm just trying to think it through, like, how do you get all this information and then look at it across all these different species. And at some point, you know, look looking at it against humans also.Ashley Zehnder: Yeah. I'll let Linda talk about the genomics side. I'll comment on sort of some of the validation, some of the externally curated data that Linda talked about. I think this is actually becoming a really important data set. It was a little bit of a slow burn to figure out how to get it and to curate it. But there are a lot of studies now coming out and not just your traditional model organisms, but naked mole rats and long lived rock fishes and primate studies and bats and all kinds of people looking at genomics and RNA seek metabolomics and proteomics across these species that have interesting phenotypes. The problem is, every one of those researchers really heads down on their own species of interest, right? Nobody's saying, oh, well, actually, we're seeing the same genetic signature in these bats that we're seeing in the naked mole rats that we're seeing in some of these long lived fish. Right. But that data is not in a very friendly format. So we were like originally we were like, okay, we're going to write some scripts, we're going to try to pull some of the stuff out of supplemental tables. It's going to be awesome. No, no, no. We have very highly trained curators who work on this data and bring it in. And we have a very standard pipeline and a process and a way to normalize the data across different studies and standard ontologies and ways to clean up this data in a way that it can be integrated with the genomics coming out of the platform. And that is a tedious and painful and ongoing effort to bring in all this data.Ashley Zehnder: Now, we have data from well over 330 individual studies, over 30 species. I think Linda, you told me it was like more than 800,000 gene entries at this point that's curated and that's kind of growing month over month. So now that's becoming part of our defensible moat, is that we've taken the last two or three years, again, slow burn, pulling all this data together in a way that it can be reused. And now we can turn a paper around and put it on a platform in a week or two. So we're kind of always scanning for these studies. But yeah, it's, it's, it's out there, but it's not always in a usable format without a lot of pain and effort. And so we've kind of put that pain and effort into getting that data in a place that we can use it. And then, of course, the comparative genomics is like a whole 'nother level of complexity.Linda Goodman: Yeah, so I can talk a little bit about how we do that within the comparative genomics community and how we've done that for Zoonomia. Because I referenced before that we like to do these sorts of studies to examine the genomes of hibernate ers and non hibernate and figure out what's different. And you'd think it would be a trivial question who is a hybrid nature amongst mammals? But it's actually not. And so along with our collaborators Alison Hindle and Cornelia Santer, as part of the Genome Project, Fauna tried to go through and categorize every every genome that was in Zoonomia. So we're talking about around 250 mammals for is it a hibernater, or is it not? And you'd be surprised how often it was digging through literature from the 1970s and someone would say, this animal is not often seen during the winter. So we think it hibernates and it's not always the most satisfying. And so it is an extremely tedious effort, but well worthwhile to go through and say this animal, I'm very sure, hibernates. This one, I'm very sure does not. And then there's this third category of animals that were unsure about we're going to remove those. And it's tedious, but you have to do that part, right? Because if you do the analysis with bad data, you're never going to find the genes that you want. And Linda, I remember you telling me when you were going through this very painful process, I think your threshold for being a perpetrator, quote unquote, was that you could drop your metabolism like 50%. Correct me if I'm wrong, and humans could go down to like 40 like in certain instances, like humans are almost there. You know, it's it's hard to know when there is only one paper about it, but certainly there are some really deep meditative states and humans and low oxygen environments where, you know, we're getting kind of close to the area where we might say that that's a hibernated, but certainly not the duration that you get out of hibernation. But it's it's it surprised me to see how close how much how much metabolic flexibility there really is when you start to look at it. Yeah.Harry Glorikian: Yeah. We've got to go talk to the monks.Linda Goodman: Absolutely. Absolutely. You know, we have that in mind. It sounds like an interesting travel experience. Yeah.Harry Glorikian: So I want to jump back for a second because. You guys don't necessarily have from what I have pieced together, the normal sort of like startup story. Right. First of all, you're an all female founding team, right? Highly unusual, right? Not something I see every day. You guys started at an accelerator program in San Francisco called Age One.Ashley Zehnder: Age One.Harry Glorikian: And then you moved to QB3 and the East Bay Innovation Center.Ashley Zehnder: Yep.Harry Glorikian: And then I think they helped you with some paid interns.Ashley Zehnder: Well, we got some from Berkeley. Yep, we did.Harry Glorikian: Yeah. And then you went through a SBIR grant.Ashley Zehnder: A couple of them.Harry Glorikian: From the Small Business Administration. And then a small business technology transfer grant from the Human Genome Research Initiative at NIH. Right.Ashley Zehnder: Yep.Harry Glorikian: I'm hopeful, hopefully my notes are all correct. Talk a little bit about the on ramp or infrastructure today for sort of seed stage startups like you. I mean, what were the most important resources?Ashley Zehnder: This is such an important conversation. I'm really glad you're asking this question. We had a call with a reporter from Business Insider yesterday who was talking to all three of us about this early founder ecosystems in biotech and sort of East Coast versus West Coast ways of starting biotechnology companies. Right. And that is a whole do a whole podcast on that, let me tell you. But I will say that there are a lot of resources for, let's call them founder led bio. Right. In the West Coast, which is kind of the buzzword these days, but people really supporting the scientists who originate the concepts and training them to be founders as opposed to assuming that you need to bring in an experienced CEO to run a company at this stage. Right. So I think we were very fortunate to meet Laura Deming at Stanford, who is one of the founding VCs. And longevity before that was a buzz word, right? She was one of the first longevity funds, literally Longevity Fund, and is really been a champion of founders, starting companies and really training founders to start companies who are deep science founders. So we started in age one. It was the first batch of age one. We're still very close to that cohort of companies doing interesting things from machine learning and image analysis through pure therapeutics development. And then Laura really helped us, her, her. We asked her later, like, why did you end up investing in us? She said, Well, the science was amazing.Ashley Zehnder: This is totally a field with so much promise. I just needed to teach you guys how to pitch. The science was there, right? So she helped me just how to pitch and how to use less science words in our pitches, which we're still working on to some extent. But then it was this balanced approach of taking in some venture money to really support the growth of the company, but balance with some of this non-dilutive funding for specific projects where it made sense and some of that was some of that in the early stage is validation, right? Having having funding through groups like NHGRI, having an early partnership with a company like Novo Nordisk, which provided also some non-dilutive funding for the company, really validated all of the science that we were doing because we were first time founders, because we're a little bit outside of the normal profile. For me, I don't feel weird being a female founder only because 80% of veterinarians are female. Like, I'm used to being in a room with all women. You go to a bio conference, it's not the same thing, right? So for us, we're just we are who we are. Right. But it's helpful, I think, to get some of that external validation and then really be able to use that to to start to build on programs and show progress.Ashley Zehnder: And then it becomes more about the data and the progress and what you can do with it. So that's a lot of how we started the company. There's I said there's a lot of support in the West Coast for this kind of thing. There's great programs like Berkeley Foreman Fund Talks, which I worked, which I was in as well, just about logistics around starting companies. There's a lot of good startup accelerators. I've got a really amazing all of us, how amazing a network of founders who we can reach out to on different. I got four or five different Slack channels of founders that I could reach out to for all kinds of advice. And usually it's always good to have a company that's one or two stages ahead of you, like talking to folks who IPO'd or something last year is is not as helpful as folks who recently raised a series B, right. And figuring out what those milestones look like and then particularly those that have taken mostly money from tech investors like we have all the lifeforce capital who led our last round is also has funded some very good therapeutics companies, Sonoma Therapeutics and Second Genome and other therapeutics companies as well. So I think it's it's helpful to see how people balance the needs of the companies at different stages in what you need.Harry Glorikian: But so do you guys think that you could have started Fauna ten years ago? I mean, did the support systems exist for starting a company like this?Ashley Zehnder: Well, no, for two reasons. We couldn't have started Fauna ten years ago. One is the data just simply wasn't in a place that the company was a tractable strategy. Everything was still too expensive and we had really shitty genomes for a few species at that point. And B, I think there really wasn't the kind of groundswell of support for deeply scientific technical founders to start their own companies and train them to be the kind of leaders they need to be to run those companies for a longer term. So I think it's a confluence of those things and being in an environment like Stanford that really encourages people to to try startups, it's not a crazy idea. Like people don't look at you like you're your heads backwards. If you start to start a company at Stanford, it's like, okay, cool. Like, when are you launching? You know.Harry Glorikian: I think it's the opposite.Ashley Zehnder: Yeah, exactly. Exactly. Like, why aren't you have a company yet? Whereas you know, a lot, many, many, many, many other places like that is seen as a very strange thing to do. So I think the environment plays a huge role. Yeah, for sure.Harry Glorikian: Yeah. I think between East Coast and West Coast too, there's.Ashley Zehnder: That's a whole, we should have a whole 'nother podcast on that.Harry Glorikian: Yeah. Yeah, exactly. Well, I live here and I was I was born and raised on the West and I remember there and I came here and I was like, Oh, this is where you are not in Kansas anymore. Like, this place is different. So, I mean, I'm hoping that the East Coast is actually embracing risk a little bit more and sort of stepping out on the edge. But it's really slow. They don't call it New England for nothing. So. But, you know, it was great having you both on the show. I this was great. I we covered a lot of ground. I'm sure people's heads are spinning, thinking about, you know, you know, different animal species and how that's going to play into this. And I mean. It really does sound like I know we have to do the hard work, but there's a lot of computational effort that has to go on here to sort of. Make sense of this and bring it all together and align it so that you can be looking at it properly and make the right decisions going forward.Ashley Zehnder: Yep. Millions of data points coming together to find drug targets for sure.Harry Glorikian: So thanks for being on the show. And you know, I wish you guys incredible luck.Ashley Zehnder: Thanks, Harry, so much. This was fun.Linda Goodman: Thanks for having us.Harry Glorikian: Thanks.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

When you hear people use the phrase "It's a hits-driven business," they're usually talking about venture capital, TV production, videogames, or pop music—all industries where you don't make much money unless you come up with at least one (and  preferably a string of) massively popular products. But you know what's another hits-driven business? Drug development. This week, we present the fourth and final episode in the Persistent Innovators miniseries, originally produced for InnoLead's Innovation Answered podcast and republished here for Soonish listeners. It's all about the giant Swiss pharmaceutical company Novartis, maker of more than a dozen blockbuster drugs like Cosentyx for psoriasis, Entresto for heart failure, and Gilenya for multiple sclerosis. Because companies lose patent protection on their old drugs after 17 years, they must constantly refill their pipeline of new drugs—and Novartis has done that by placing a huge bet on the Novartis Institutes for BioMedical Research (NIBR), its 2,000-person R&D lab based in Soonish's hometown of Cambridge, MA. In this episode you'll meet Tom Hughes, a biotech entrepreneur and former Novartis executive who helped to set up NIBR in the early 2000s, as well as NIBR's current president, Jay Bradner. They explain why the decision to build NIBR was initially controversial even inside Novartis, and how the labs are structured today to take big but manageable risks and ensure that the company can capitalize on biology's growing understanding of the molecular and genetic underpinnings of disease."I find from the top down, our chairman to our CEO, to every commercial leader, there is a tolerance and an appetite for bravery in drug discovery that is really refreshing and honestly very empowering," Bradner says of Novartis. "If you looked at the type of programs in our portfolio, they're not for the faint of heart. And this is for a very specific reason. We worry that if we don't try to [do it] well, then who will?""What Makes Novartis a Persistent Innovator?" was first published by Innovation Answered on February 28, 2022. You can hear the entire miniseries at innovationleader.com or in your podcast player of choice.Logo photo by Sangharsh Lohakare on UnsplashFull transcript available at http://www.soonishpodcast.org/505-novartis

As we finish up we focus on the contemporary management of systolic heart failure or so called heart failure with reduced ejection fraction. Our focus in this episode is on RAAS blockade which includes the aldosterone antagonists along with a new kid on the block, Entresto. How does Entresto compare and where does it fit in to our contemporary management of systolic heart failure? We'll discuss that, along with the reason why we dont see much Digoxin anymore. When we're done, we'll have a very complete contemporary approach to how best to use pharmacotherapy in our patients with heart failure.

This week, the top managed care news included Entresto winning the first FDA nod in a hard-to-treat type of heart failure; President Joe Biden nominates a new CMS administrator; experts discuss the potential for Biden health reforms.

FirstWord Pharma PLUS editors Michael Flanagan and Simon King discuss the week's most important news in pharma and biotech, including positive data for Keytruda and Lenvima in first-line renal cell carcinoma which was presented at ASCO-GU, more data for Eli Lilly's diabetes treatment tirzepatide, expanded approval for Novartis' Entresto and gene therapy concerns for bluebird bio.

An FDA warning over pharma company's promo material; Entresto's approval is expanded, There's approvals in homozygous familial hypercholesterolemia and chronic inflammatory demyelinating polyneuropathy; And a migraine device for OK'd for teens.

Í þessum þætti leiðir Hjálmar Ragnar Agnarsson, héraðslæknir og aðjúnkt við Háskóla Íslands, okkur gegnum langvinna hjartabilun. Hver er munurinnn á HFrEF og HFpEF? Hvernig á að haga vökvagjöf í hjartabiluðum einstaklingum? Hvernig skal meðferðinni háttað og eru einhver lyf mikilvægari en önnur í þeirri meðferð? Að lokum er farið yfir nýjungar í hjartabilunarmeðferð, þar á meðal SGLT2 hemla og fleira.

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: I'm Greg Hundley, associate editor from the VCU Pauley Heart Center in Richmond, Virginia. Dr Carolyn Lam: Greg, amyloid cardiomyopathy is the rage. I cannot tell you the number of discussions I've had on the topic. Of course, it was tafamidis, the amazing results with that trial that really made us realize we need to pick this up. But have you ever thought about the cost effectiveness of tafamidis for amyloid cardiomyopathy? Well, guess what? We're going to have a whole feature discussion just about that. But first let's go to our summary, shall we? Dr Greg Hundley: You bet, Carolyn. Well, let me get started. I'm going to talk about regulation of cell cycle growth as well as division in regard to cardiac regeneration. My first paper comes from Dr Lior Zangi from the Mount Sinai School of Medicine. Well, Carolyn, have you ever wondered why the adult mammalian heart has limited regenerative capacity? Dr Carolyn Lam: All the time, Greg. Dr Greg Hundley: Well, of course you have. It's mostly due to postnatal cardiomyocyte cell cycle arrest. In this study the investigators evaluated the effect of pyruvate kinase muscle isozyme 2 and cardiomyocytes through models of loss, that is cardiomyocyte specific PKM2 deletion during cardiac development or gain using cardiomyocytes specific PKM to modified mRNA to evaluate PKM to function and regenerative effects post-acute or chronic MI in mice. Dr Carolyn Lam: Nicely described. What did they find, Greg? Dr Greg Hundley: What they found is that PKM2 is expressed in cardiomyocytes during development and immediately after birth, but not during adulthood. Using cardiomyocytes PKM to modified RNA, they found that cardiomyocyte targeted strategy following acute or chronic MI resulted in increased cardiomyocyte cell division, enhanced cardiac function, and improved long-term survival. They found that PKM2 regulates the cardiomyocyte cell cycle and reduces oxidative stress damage through anabolic pathways and beta-catenin. Dr Carolyn Lam: Cool, Greg. Man, this cardiac regeneration really, really is a hot area. Dr Greg Hundley: Carolyn, that is so insightful because these results really impact research toward unlocking pathways that could be involved in induction of myocyte cell division and regeneration in those sustaining MI or conditions like MI. Dr Carolyn Lam: Nice. Well, Greg, I'm going to change tones here and ask you, can we prevent atrial fibrillation with treatments for diabetes? Well, guess what? We have a paper next. It's from Dr Wiviott from the TIMI Study Group and his colleagues who really reason that since atrial fibrillation is associated with hypertension, obesity and heart failure in patients with diabetes and SGLT2 inhibitors have been shown to lower blood pressure, reduce weight, and reduce hospitalization for heart failure in these patients, perhaps SGLT2 inhibitors may also reduce the risk of atrial fibrillation. They explored the effect of Dapagliflozin on the first and total number of atrial fibrillation and atrial flutter events in patients from the DECLARE-TIMI 58. As a reminder, they had type two diabetes with either multiple risk factors for or known atherosclerotic cardiovascular disease. Now importantly, atrial fibrillation events were identified by a search of the safety database using these MedDAR preferred terms. Now what they found was Dapagliflozin reduced the risk of atrial fibrillation events during follow-up as well as the total number of atrial fibrillation events in patients with type two diabetes. These reductions were consistent across major subgroups including sex, presence of atherosclerotic cardiovascular disease, history of atrial fibrillation, history of heart failure, history of ischemic stroke, HBA1C groups, body mass index groups, blood pressure or EGFR. They looked at all these subgroups because these are all clinical factors, well established, with associations with the risk of atrial fibrillation. Dr Greg Hundley: Wow, Carolyn. Another sort of feather in the cap for the SGLT2 inhibitors. What does this mean for clinical practice? Dr Carolyn Lam: Ah. I'm not going to answer it here. I am going to say everybody has to read the excellent editorial by Dr Granger from Duke University and Dr Mahaffey from Stanford University School of Medicine. But what I will tell you is their concluding sentences. They said, "This report provides evidence that Dapagliflozin appears to reduce atrial fibrillation events in patients with diabetes and coronary disease and multiple risk factors. It also raises the issue of how to determine when effects on a secondary outcome, particularly one collected without the rigor of systematic collection using perspective definitions and case report forms, whether or not these are reliable." So must read. Dr Greg Hundley: Absolutely. Carolyn, my next study comes and evaluates arrhythmogenic right ventricular cardiomyopathy and is really investigating the concept of auto immunity, looking at associations of circulating anti heart and anti intercalated disc auto antibodies with disease severity and family history. The paper comes from Professor Alida Caforio from the University of Padova. Again, looking at the role of auto antibodies in patients with ARVC. An interesting topic. Dr Carolyn Lam: Yeah, that's really novel. What did they find? Dr Greg Hundley: They investigated ARVC pro bands, so those that sort of started with the disease process in a family and noted an increased frequency of serum organ specific anti heart autoantibodies and anti-intercalated disc autoantibodies in a sizeable arrhythmogenic RVC cohort as compared to controls. They found that positive AHA status. Dr Carolyn Lam: Anti-heart antibodies. Dr Greg Hundley: Yep. Was associated with lower left ventricular ejection fraction, a higher frequency of cardiac symptoms and implantable cardioverter defibrillator implantation. Positive AIDA was associated with lower ejection fractions in both the right and the left ventricle. Dr Carolyn Lam: AIDA being the anti-intercalated disc auto antibodies. Wow. That is interesting. But what are the clinical implications? Dr Greg Hundley: Well, the presence of both these organ specific AHA and AIDA antibodies provides evidence of autoimmunity in the majority, so 85% of familiar, and almost half, 45%, of sporadic ARVC. In programs and in effective relatives, these antibodies were associated with the disease severity features. So really a link with this auto immunity and ARVC. Dr Carolyn Lam: Yeah. I never thought of ARVC as an autoimmune disease. Very interesting. But let me also tell you what else is in this week's issue. There are letters to the editors, one from Dr Kaski regarding the mag STEMI randomized control trial questioning whether improving coronary vasal motion can be equated to restoring patient's cardiovascular health. Interestingly with a letter in response from Dr Sabatine. There's also a research letter by Dr Alahmad on the cardiovascular mortality and exposure to heat in an inherently hot region and where they were was Kuwait. They also drew some implications for climate change. Very interesting piece. There's also an ECG challenged by Dr Verma describing conduction abnormalities and ischemic cardiomyopathy in an 84-year-old man. Dr Greg Hundley: Very nice. Carolyn, in the mailbag, there's a nice research letter from Dr Nicholas Leeper from Stanford University School of Medicine. It's entitled “The 9p21 locus promotes calcific atherosclerosis.” Our own Josh Beckman has an on my mind piece regarding “The Big Mac Attack on Peripheral Arterial Disease.” Dr Carolyn Lam: I love that. I just love the titles Josh comes up with. Dr Greg Hundley: Then finally Bridget Kuehn has a very nice sort of correspondence on Cardiovascular News regarding cardiac imaging on the cusp of artificial intelligence. What a revolution we have ahead, Carolyn, and I know that's a topic that's true to your heart. Dr Carolyn Lam: It is. I loved her paper. Dr Greg Hundley: Okay. Carolyn, how about we get onto that feature article? I'm waiting to hear about the cost effectiveness of tafamidis. Dr Carolyn Lam: Me too. Dr Greg Hundley: Well listeners, we have got a great discussion for our feature publication today and we have Dr Dhruv Kazi from Beth Israel Deaconess in Boston and our own associate editor, Dr Justin Ezekowitz from University of Alberta. Well, as we get started, Kazi, can you tell us a little bit what was the hypothesis that you wanted to test with this study and maybe even before that a little bit of background with transthyretin amyloid and tafamidis? Dr Dhruv Kazi: Yeah. Transthyretin amyloidosis is a subgroup of patients who present with heart failure with preserved ejection fraction, which we know is a heterogeneous condition that has been pretty resilient to effective guideline directed therapies over the past decade. It's a subgroup of patients generally presenting in their 70s with slowly declining quality of life and a median survival of about three years. It hadn't had an effective therapy before and so when tafamidis, which is a stabilizer of transthyretin and prevents its deposition in the myocardium, was developed and tested in a randomized clinical trial that showed an improvement in survival, a reduction in heart failure hospitalizations and a slowing of decline and quality of life. It was viewed as a really big win for the heart failure community. What came as a surprise though is the pricing. It was launched in 2019 at $225,000 a year. We set out to ask, given that this is a severe disease without alternative treatments, is this price tag generating enough value? Is this a cost-effective therapy? The background here again is that oncologic therapies have had a long history of very high prices for rare diseases and severe diseases. But this is the first time we're seeing this in cardiology. Can we think more broadly about how we're going to tackle this issue? Not just for tafamidis but also for other drugs that come down the pipe. Dr Greg Hundley: Wow. $225,000 per year. Tell us what was your study design, and how did you go about evaluating this issue? Dr Dhruv Kazi: We started off with the one phase three trial of the drug that has been published and simulated in a mathematical model the population that would be eligible for this therapy, reproduced the events, heart failure hospitalizations, debts, quality of life that were seen in the trial for the first three years, and then extrapolated beyond the trial based on what we know about HFpEF and what we know about transthyretin amyloidosis. It's a mathematical model that first reproduces what was seen in the trial and then extrapolates beyond what we think is the best guess of what happens to these patients. We tested a variety of scenarios whether the drug continues to be effective, whether the effectiveness declines over time or the effectiveness ceases immediately after three years. Dr Greg Hundley: What did you find? Dr Dhruv Kazi: What we found was interesting and it surprised us a little bit, which is that in the base case, which is assuming that the drug stays effective beyond three years, the drug is actually very effective in the traditional sense. It added 1.3 quality adjusted life years. For context here, this is about twice the effect size you expect to see with Entresto, and the HFpEF patients. So here's a drug that we've accepted and HFpEF has part of guideline directed medical therapy. Tafamidis in that best-case scenario is about twice as effective, but it is not cost effective. Because you're paying $225,000 for every year that the patient is on the medication, its incremental cost effectiveness ratio compared with usual care was $880,000, so well above what we would consider value for money. That's the best-case scenario assuming that the drug is permanently effective, if the drug's effect wanes over time, which is very likely as these patients get older and sicker, then the drug gets even less economically attractive. Dr Greg Hundley: You've pointed out in your article, if you had 120,000 transthyretin patients in the United States, that would translate to how many dollars? Dr Dhruv Kazi: We estimate that if all of those 120,000 patients received tafamidis, the healthcare spending would go up by $32 billion a year and most of it is towards the drug. But the caveat is that we think 120,000 patients in the US is a very conservative number because the diagnostic technology for amyloid cardiomyopathy has improved substantially over the last five years so that we no longer need biopsies. We can use nuclear scans to diagnose the disease and we have pretty good to genetic testing to identify the genetic variant of the disease. We think that number is probably closer to 200,000 or even higher because the healthcare expenditure is almost entirely driven by drug costs. The more patients we diagnosed, the bigger the budget's impact on healthcare spending. Dr Greg Hundley: Oh my. Well Justin, for our listeners, Justin resides in Canada. Justin, what do we do with these results? I mean this is quite a sticker shock for probably an important therapy for this patient population. Dr Justin Ezekowitz: Greg, it's a great issue and Kazi, thank you very much for this terrific, easily understandable manuscript that I think everybody should read as it's very well written and easy to understand for us non-health economists. The sticker shock is a bit of a tricky one because we always want to do what's best for our patients. When we look at that budget impact analysis, the challenge is what do we think internationally? The US is critical in terms of understanding this, but then for the rest of the world, there's certainly almost no willingness to pay at this threshold and with an uncertain incidence of amyloidosis globally, but also within the US and Canada and the difficult in diagnosis already, I think we're going to have to realize what can we do for our patients and who benefits the most with this drug given its importance and its efficacy? Kazi, you mentioned another thing which I think is critical is what happens after 30 months if the effect wanes and where does that take us for the impact on cost and effectiveness over time but also the budget impact analysis? Because the second drug or third drug may very well come along that may fill that niche. Dr Dhruv Kazi: Justin, that's a really good question. I mean the study only goes to 30 months and that's the only one randomized trial for tafamidis that we're working off of. So there's substantial uncertainty about what happens to this drug beyond 30 months. It's reasonable to assume that some of the effect persists, that as patients get older, get sicker, that effectiveness will wane over time. Which ties very closely to the cost effectiveness. So if the patients continue to take the drug but it's not as effective as you can imagine, it becomes less cost effective. This also has implications for other drugs coming down the pike, which may or may not be more effective than tafamidis. They may or may not be tested head to head with tafamidis. Physicians are going to be left with the question, very clinically relevant question, of which drug to start with, how do you switch on them the next generation or more expensive drugs that come down the pike? We'll have to rely on both real-world evidence and to some extent mathematical modeling to use our best judgment on developing a treatment strategy for these patients. But rest assured that our current regulatory framework means that the drugs coming down in the future will be more expensive than tafamidis and hence, this is a good time to have the conversation about cost effectiveness and our willingness to pay for innovation. Dr Greg Hundley: What needs to happen next to help either lower cost or develop some sort of competition in the treatment of this disease to lower the cost? Dr Dhruv Kazi: I can take a stab at that. Greg, I think the findings of this particular drug in transthyretin amyloidosis is illustrative of the challenges that lie ahead. I think there are clinical research and policy implications. As clinicians, it's really important for us to know that this high cost of the drug is not a theoretical challenge. It's a practical challenge for our patients. The majority of these patients are going to be on Medicare part D. We estimate that the out of pocket costs is going to be in the range of $8,000 to $9,000 a year even with Medicare part D, which is a big amount of money for our fixed income seniors. I encourage our clinicians to have this conversation about out-of-pocket costs with patients, not just when you start the therapy but throughout the year. We know that the Medicare part D copays change over the course of the year based on where they are in the insurance plan. Having this conversation may help preclude costs related non-adherence. We might be able to identify patients early or at risk, put them into patient support programs or switch them to alternate therapies that may not be as effective but at least are likely to offer the patient some support. From a research perspective, we really need to figure out what subgroup of patients are more likely to benefit. Let's say we have 200,000 patients with transthyretin amyloidosis in the US. We need more research, and the company is not going to be vested in doing this research, it's going to have to be NIH funded research to identify subgroups of patients who benefit most from this drug, both in the short term and over the long term. From a policy perspective, what this drug pricing issue is telling us is that we provided incentives for companies to innovate in the rare disease orphan drug program. These incentives are working. More than half of the drugs that are coming out now or have in the past year are under this rare disease umbrella. But these drugs, once they're approved, are super expensive. We need to figure out a regulatory framework where we continue to incentivize innovation for rare diseases for orphan drugs, but at the same time tie those incentives to the final pricing to ensure that the patients get access to the drug and not just the wealthy patients who can afford the copays, but all patients who would benefit from the drug. One of the things that comes to mind as clinicians and researchers is that particularly in cardiology, we are obsessed with innovating, with regards to new molecules and new technology. I would like us as a community to focus not just on molecules but also on markets because the innovation is not meaningful if our patients cannot have access to them. This year being the presidential election year, we're going to hear a lot about drug pricing. What I hope that this example shines a light on is that drug pricing is complicated and trying to figure out the right framework to incentivize innovation while it's still ensuring access is going to take thoughtful interventions, regulatory interventions, and clinicians should very much be a part of that process. Dr Greg Hundley: Well listeners, we've heard a wonderful discussion here highlighting a new therapy for a disease process that's being increasingly diagnosed with our aging population and new technologies, magnetic resonance, echocardiography that identify this condition. But then how are we going to afford some of the therapies that are moving forward and design a system that emphasizes not only scientific discovery, but cost effectiveness? We want to thank Dr Dhruv Kazi from Beth Israel Deaconess and also Justin Ezekowitz from the University of Alberta. We hope you have a great week and look forward to speaking with you next week. This program is copyright the American Heart Association 2020.

Sacubitril/Valsartan, known as Entresto, is a new dual drug therapy that includes an angiotensin receptor inhibitor and is indicated to reduce the risk of cardiovascular death and hospitalization in patients with chronic heart failure.  Since its approval for the treatment of chronic heart failure with reduced injection fraction, a commonly raised question is whether treatment with this drug challenges the use of B-type natriuretic peptide, or BNP, testing compared to the N terminal proBNP assay because Sacubitril may interfere with BNP clearance. The clinical and analytical studies addressing this issue are limited, along with the fact the diversity of both BNP and NT-proBNP assays used in clinical laboratory practice have not been adequately evaluated in clinical trials or studies to provide an evidenced-based on final decision as to what assay or assays should be used or eliminated from use when a patient is on Entresto. In the September 2019 issue of Clinical Chemistry, a Q&A feature titled, “Role of BNP vs NT-proBNP Testing in the Age of New Drug Therapies” asked five experts with different roles in this field to discuss this issue. 

This week: New Invokana approval; More ranitidine recalls lead CVS to suspend all sales; FDA has identifies 11 serious cybersecurity vulnerabilities that could affect medical devices and hospital networks; Entresto indication expanded; and COPD investigate treatment is rejected.

B-type natriuretic peptides, or BNP, and N-terminal proBNP, or NT-proBNP, are peptides produced in the heart in response to increased wall stretch and volume overload.  Their production and secretion increases in the heart with the progression of heart failure and they have emerged as useful heart failure biomarkers.  Since the discovery of BNPs in the 1980s, much effort has been made to precisely determine the BNP and NT-proBNP levels via immunoassays for reliable heart failure diagnostics. Entresto™ is a new heart failure therapy that includes sacubitril as one of its components.  Sacubitril is a specific inhibitor of neprilysin. This is a zinc-dependent metalloproteinase that cleaves various peptides including BNP.  In fact, augmentation of circulating BNP due to neprilysin inhibition is considered as a possible mechanism of Entresto’s positive effects.  A paper appearing in the October 2019 issue of Clinical Chemistry examines the circulating products of BNP proteolysis by neprilysin and how they might reflect impact on the metabolism of active BNP. 

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, associate editor and director of the Pauley Heart Center at VCU Health, in Richmond, Virginia. Dr Carolyn Lam:                So Greg, are ARNI's now going to be used for functional, mitral regurgitation and heart failure? Well, we're going to be chatting all about that with our feature paper, coming right up after these summaries.                                                 Greg, you've got a biggie to start with, haven't you? Dr Greg Hundley:             Oh yes, Carolyn, I'm really excited about this paper. The senior author Wanpen Vongpatanasin from University of Texas Southwestern Medical Center in Dallas and looking at high phosphate diets and their relationship to exercise intolerance. I really felt this was an exceptional study and combining that key that we have, for basic science papers and translation, where we're looking at data from both human and basic science, in both in a single manuscript.                                                 So, this study focuses on inorganic phosphates and they are present in 40-70 percent of the foods, really as a preservative enhancer, in western diets. We see it in colas, meats, dry food mixes, bakery products.                                                 For the human subject component of this study, the investigators examine the relationship between physical inactivity, assessed with ActiGraphs that were worn, and serum phosphate levels. They also obtained MRI measures of cardiac function and participants were recruited from the Dallas Heart Study too.                                                 In animals, they looked at the direct effects of dietary, inorganic phosphate on exercise capacity, oxygen uptake, serum non-esterified fatty acids, and glucose was measured during exercise treadmill tests in mice fed either high inorganic phosphate diets or normal in-organic phosphate diets. And they were on that for 12 weeks.                                                 To determine the direct effect of phosphate on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in the differentiated myotubes were conducted after subjecting those cells to media with high or low phosphate conditions. Dr Carolyn Lam:                So, what did the study show? Dr Greg Hundley:             In the human part, among 1603 participants, higher serum in-organic phosphate was independently associated with reduced time spent in moderate to vigorous physical activity and increased sedentary time. And interestingly, there was no association between serum phosphate levels and left ventricular ejection fraction or volumes.                                                 In the animal studies, mechanistic insight was obtained. Compared to controlled diets, consumption of high phosphate diet for 12 weeks did not alter body weight or left ventricular function, thereby confirming what we saw in the human subjects, but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, fatty acid levels, and led to down-regulations of genes involved in fatty acid synthesis.                                                 So, the take-home on this is that the results of this study demonstrate a detrimental effect of dietary, phosphate excess on skeletal muscle, fatty acid metabolism, and exercise capacity, which is independent of obesity and cardiac contractile function.                                                 And as such, dietary in-organic phosphate may represent a novel and modifiable target to reduce physical inactivity associated with the western diet. I think, Carolyn, we're going to see a large number of epidemiologic studies that are going to really look at this as something we might be able to modify in our diet to help impact some of these sedentary lifestyles and the harmful cardiovascular effects that we find associated with that lifestyle. Dr Carolyn Lam:                Yikes. Remind me again, so phosphates in colas, meats, dried food mixes, and bakery products and so on, the preservative. Wow, you're right; big paper. Dr Greg Hundley:             It's amazing. It's in 40-70 percent of the food products here in the United States. So, wow. Something really striking. So Carolyn, how about one of the papers that you liked? Dr Carolyn Lam:                Moving to related cardio metabolic disease, we know that patients with type 2 diabetes and prevalent atherosclerotic cardiovascular disease, there is a tenfold variation in future cardiovascular risk in these patients. The current paper actually analyzes data from EMPA-REG OUTCOME where the authors, led by David Fitchett from St. Michael's Hospital in Toronto, sought to investigate whether the beneficial effects of Empagliflozin, observed in the EMPA-REG OUTCOME trial, varied across the spectrum of baseline, cardiovascular risk.                                                 What they found was that in patients with type 2 diabetes and atherosclerotic cardiovascular disease, the relative reductions in risk of cardiovascular death, all-cause mortality, 3-point MACE, and heart failure hospitalizations with Empagliflozin versus placebo, were consistent in patients with and without a prior, myocardial infarction, with and without a prior stroke, and across sub-groups by the 10-point TIMI Risk Score for secondary prevention at baseline. Dr Greg Hundley:             Does this suggest, Carolyn, that we use these inhibitors in all patients with type 2 diabetes? Dr Carolyn Lam:                Remember the EMPA-REG OUTCOME; all patients had established atherosclerotic cardiovascular disease. This paper really adds to the understanding of the gradient of risk within these patients who had atherosclerotic cardiovascular disease and says Empagliflozin could be beneficial. But remember, there are patients with type 2 diabetes without established, cardiovascular disease and I think there's still equipoise in this primary prevention population. Dr Greg Hundley:             That was great, Carolyn. Now I'm going to grab another sip of coffee and go onto my next paper. Dr Carolyn Lam:                Sure, as long as it's not cola. No phosphates. Dr Greg Hundley:             Right, thank you very much, Carolyn. I'm going to talk about screening for small and medium abdominal aortic aneurysms. This particular study comes from the surveillance of the National Health Service screening program by Dr Earnshaw. Basically, population screening for abdominal, aortic aneurysms has been shown to reduce AAA-related mortality by up to 50%. Most men who screen positive have a AAA below 5.5 centimeters in diameter, and that's really our current referral threshold for treatment. When they have smaller diameter aneurysms they're entered into an ultrasound surveillance program.                                                 In this study, the investigators looked and reviewed those that had small, 3-4.4 centimeter diameter aneurysms or medium ,4.5 up to 5.4 centimeter aneurysms, and they were followed. They were looking at the risk of rupture in these under surveillance.                                                 They had a total of 18,652 men and the risk of rupture overall per annum was 0.03% for men with small, abdominal aortic aneurysms and 0.28% for medium size. That was just below the threshold for the 5-5.4 centimeters, which was 0.4% over time. The risk of abdominal aortic aneurysm surveillance is below .5% per year and that is just below our current referral threshold for surgery, which is 5.5 centimeters.                                                 This is a study that really confirms, Carolyn, that the target mark or diameter that we've selected is appropriate. Dr Carolyn Lam:                Nice. These just confirm the current guidelines? Dr Greg Hundley:             Yeah, they do and Gil Upchurch from University of Florida, a surgeon, had a very nice editorial. The point he wants to make is yep, diameter of 5.5 is the threshold, but a couple key points. As patients are coming in for these visits, we need to continue to emphasize to them other factors related to growth of abdominal aortic aneurysms and their rupture. So, tobacco cessation, treatment of your lipids, management of your hypertension.                                                 The other point that he makes, is we really don't need to be operating on those individuals with an abdominal aortic aneurysm diameter of less than 5.5 centimeters. He makes an argument here that's in some countries with fee-for-service reimbursement, up to 30% of AAA repairs are for aneurysms less than this diameter of 5.5 centimeters. This over utilization of resources can add considerable costs to the healthcare system for managing this condition and is unlikely to increase the overall survival of these patients.                                                 A nice study confirming that what we're doing, really in terms of size and diameter, is correct, but also emphasizing this patient population often has a lot of other cardiovascular co-morbidities that we need to aggressively manage. How about your next paper? Dr Carolyn Lam:                From one very clinically, applicable paper to another. This one answers the question, what's the optimal duration of emergency department and post-emergency department rhythm monitoring among patients with syncope. And the authors, led by Dr Thiruganasambandamoorthy and his colleagues from the Ottawa Hospital Research Institute, prospectively studied adults presenting within 24 hours of syncope at six emergency departments. They collected baseline characteristics, the time of syncope, the time of emergency department arrival, and the Canadian Syncope Risk Score, risk category. They followed subjects for 30 days and adjudicated the primary outcome, which was serious arrhythmic conditions and that includes arrhythmias or interventions for arrhythmias and unexplained death.                                                 Their results showed that the overall arrhythmia risk, and the risk after two hours of emergency department arrival from Canadian Syncope Risk Score, low-risk patients, was indeed very low. Similarly, the overall risk and after six hours of emergency department arrival for medium and high-risk patients was moderate and high, respectively. No low-risk patients suffered ventricular arrhythmia or unexplained death and most of the arrhythmias among the non-low-risk patients occurred within 15 days of the index syncope. Dr Greg Hundley:             Carolyn, what's the take home message here? Dr Carolyn Lam:                The results really support brief monitoring in the emergency department for two hours for Canadian Syncope Risk Score low-risk patients, and six hours for medium and high risk patients followed by selective admissions and the results also support a 15-day outpatient monitoring for medium-risk patients at a selected threshold and for all high-risk patients. So very practical advice. Dr Greg Hundley:             Very good. Until next week, I'm going to watch out for phosphates. Dr Carolyn Lam:                Indeed, and let's go on now to our featured discussion.                                                 For today's featured paper, we are discussing the results of the PRIME Study and that is Angiotensin Receptor Neprilysin Inhibitor, or ARNIs, for functional mitral regurgitation. A terribly interesting study. So pleased to have with us an author Dr Sung-Hee Shin from Inha University Medical center in Incheon, Korea as well as our associate editor Dr Victoria Delgado from University of Leiden in the Netherlands.                                                 Sung-Hee, what an interesting study. ARNI or Entresto for functional mitral regurgitation. Could you tell us what inspired this study and what did you find? Dr Sung-Hee Shin:            Our study was the designed to tell if ARNI or functional mitral regurgitation because secondary functional mitral regurgitation was developed as a result of a reduced function. Guideline-directed medical therapy for heart failure would be a mainstay for a therapy.                                                 But despite use of the traditional drugs such as BETA blocker, ACE inhibitor or angiotensin receptor blockers, you know that the functional mitral regurgitation may be common and significant in the person having this functional mitral regurgitation would be related to increased morbidity and mortality.                                                 So, that trial showed that trans-catheter mitral valve repair effectively reduced the function mitral patient and resulted in lower rate of heart related mortality among patients with heart failure and function mitral regurgitation.                                                 In our blind trial, we also tried to tell whether an ARNI is more effective in improving function mitral regurgitation and randomly assigned 118 patients with heart failure and chronic secondary function mitral regurgitation lasting more than six months despite medical therapy and ejection fraction between 25% and 50% to receive either sacubitril/valsartan or valsartan in addition to standard medical therapy for heart failure.                                                 What happened with that change of mitral regurgitation after 12 months which was assessed by means of transthoracic area ways echo. What we observed was that transthoracic area as well as the volume of mitral regurgitation saw a decrease much more effective in the sacubitril/valsartan group than valsartan group.                                                 We also looked at the various other measures of the left ventricle remodeling and showed that the valsartan group had smaller left ventricle volume at 12 months and had a greater reduction of end-diastolic volume index.                                                 Also, among the completers ARNI, for the reduced left ventricle volume and the yearly time than the control group. So, what we think is that these factors might contribute to greater reduction of function mitral regurgitation in patients in the sacubitril/valsartan group.                                                 But our study was a mechanism study, but it was not designed to see outcomes. So further research and data would be necessary to check is this transthoracic echo end point can translate into better outcome in this population. Dr Carolyn Lam:                Sung-Hee, this is just so interesting to have hypothesized this about functional mitral regurgitation. And not only that, I mean, to my mind, this is the largest echo-based studies of patients before and after Entresto that I can think of. It's nice to know, on top of knowing in paradigm that we can improve outcomes in heart failure reduced ejection fraction, that we now can look at the heart and see what happens in so many dimensions.                                                 So, congratulations.                                                 Victoria, were you surprised by these results? And do you agree with the mechanisms that Sung-Hee suggested? Dr Victoria Delgado:        I think that this study is very important because in the field of functional mitral regurgitation, there is still a lack of consensus on how to treat these patients, which are very challenging.                                                 If the patient needs revascularization they will be referred for certain. But it still should be CBR mitral regurgitation and moderate and mile mitral regurgitation are not considered.                                                 I think that we discuss often which is the optimal medical therapy or the guidelines based medical therapy but it's not really consensus because the studies before have not been like this one. That large in order to answer a specifically that question.                                                 I think that this article brings an important message and brings more evidence to our field that there is not that much data. So, I think it's very important for that research, in particularly after the research of the co-op and the mitral trial where it seems that the selection of patients is very important in order to identify the patients that will really benefit from those therapies. Dr Carolyn Lam:                That's such a good point. Going to that selection of patients, Sung-He, you mentioned very carefully the ejection fractions that you allowed up to 50% in these patients. Could you explain how you reasoned the selection of this patient cohort? Dr Sung-Hee Shin:            The reason why we chose the patients we did, the range of ejection fraction condition, was that we thought the reversibility of the left ventricle mortality and function mitral regurgitation might be more pronounced in these patients.                                                 When we considered the fraction condition in mitral regurgitation with ejection fraction used under [inaudible 00:18:17] LV dysfunction, our inclusive criteria of ejection fraction between 25 to 50% might correspond to ejection fraction of 20 to 40% in patients with mitral regurgitation.                                                 We concluded that if a patient had ejection fraction less than 25% because the reversibility of mortality and function mitral regurgitation might be smaller when all the LV dilation is too extreme and advanced heart failure is already established.                                                 So, I just thing how it can be provided to the patient who have functional mitral regurgitation associated with too extreme LV dilation and LV ejection fraction too. Dr Victoria Delgado:        I think, Carolyn, it's a very good point what she explained because we are used to select patients based on ejection fraction, in particularly patients with functional mitral regurgitation, ejection fraction is rather misleading because actually it's just a change of volume in the ventricles emptying in a low pressure chamber which is the left atrium.                                                 The moment that you correct that in mitral regurgitation sometimes then you face, or you see, the true ejection fraction of that ventricle. And if we wait too long, we may end up with ventricles that they don't have any more resource in order to improve ejection fraction after repair of the mitral valve.                                                 So, I think that this study is important to also realize that concept. That ejection fraction in patients with functional mitral regurgitation may not be the most accurate parameter to assess the function of that ventricle. Dr Carolyn Lam:                Yeah. Exactly. And I thought that was a very clever part of the design. I'm glad you explained it and also so glad, Victoria, you invited the editorial by Dr Mullens, who also commented on that. So, just for the audience to understand that ejection fraction up to 50% was included and ejection fraction less than 25% was excluded.                                                 So also, again, very consistent to your prior point, Victoria.                                                 Could I ask you, I think Dr Mullens also spent quite some time talking about the potential mechanisms. What's your take of this Victoria? ARNI for functional regurgitation. How come? Dr Victoria Delgado:        For me, I'm much more from the side of the imaging point of view. When we have patients with functional mitral regurgitation I always try to see which is the capability that that ventricle has to recover.                                                 Actually, first is always medical therapy, but we know that the [inaudible 00:20:59] only, for example, we just reduced the mitral regurgitation, but they don't really improve the function of that ventricle, while if you reduce the loading conditions of the ventricle in terms of blood pressure as well and favoring remodeling of the left ventricle, you can improve the condition of the mitral valve and reduce the mitral regurgitation.                                                 How valsartan plus sacubitril works differently than valsartan alone that I don't think that I have enough knowledge to explain why but it could be that in a way there is more effective with sacubitril on top of valsartan can improve the loading conditions of the ventricle and improve the, or facilitate, the reversing of morbidity of that ventricle, reducing the mitral regurgitation and that, by itself, could also lead to reversing morbidity.                                                 Like a little bit cardiac resynchronization we'd do, for example, in patients with an ejection fraction below 35% and based on the EEG you have the synchronous fraction of the papillary muscle or the walls of the ventricle which could lead to the mitral regurgitation at the moment that you resynchronize that mitral regurgitation can produce, you reduce part of the volume of the load of the ventricle and that can favor that reversing morbidity.                                                 So, I think that this study raises a lot of questions and I think that further research is needed in order to confirm or to know more how these treatments work. Dr Carolyn Lam:                Goodness, that was so beautifully explained and in fact, many clues from Sung-Hee's study and the reversal of left ventricle end diastolic volume index greater with those treated with ARNI, the LA size and so on.                                                 But maybe I should ask you, Sung-Hee, in line with what Victoria said, what are the next steps? Do you already know what are the next studies that you're going to be looking at in PRIME? Dr Sung-Hee Shin:            We're considering mark of monitoring such as NT pro-BNP or using auto imaging models such as echo and cardiac MRI to look at the change of mitral valve regurgitation in more detail.                                                 This kind of study might be very helpful in understanding [inaudible 00:23:15] ARNI in functional mitral patient. Dr Carolyn Lam:                Yes, that's clever, too. And Victoria, before we end could you maybe give us some take home messages? Dr Victoria Delgado:        I think that the take home message from this study is that when we have patients with functional mitral regurgitation, we need to think what we can offer to them. Not consider mitral regurgitation just as a base standard. That it's going to respond only to diuretics. No. We need to do something on that left ventricle to help it to improve the function and to avoid the progress to more reduced function.                                                 It's very important to understand the mechanism of the mitral regurgitation and to use the guidelines based medical therapy trying to go step by step in order to optimize the medication of that patient and later on, see all the potential treatments that are available right now such as cardiac synchronization therapy, which we should not forget, and then surgery if the patient needs catheterization and if the patient needs the benefit from mitral valve plasty or eventually, for example, trans catheter mitral valve therapies.                                                 But we should avoid that the patient goes further down into heart failure with very dilated ventricles and very poor function because then probably we may face a point of no return. Dr Carolyn Lam:                Thank you so much, Victoria. Both you and Sung-Hee mentioned this is a mechanistic study. So many insights. But it's not saying that everybody with functional mitral regurgitation has to be treated this way now. It's calling for more work and it's certainly very, very important study.                                                 Thank you listeners, for listening today as well. You've been listening to Circulation on the Run. Don't forget to tune in again next week.                                                 This program is copyright American Heart Association, 2019.  

Beth Davidson, a nurse practitioner who specializes in heart failure management in Nashville, TN, and heart failure patient Michele N, discuss the problem of heart failure, providing insight into the impact on African Americans specifically, the symptoms, and managing the condition. Listen to more health-related stories and research updates at www.hpr.fm

A review of the ARNI approved for the treatment of HFrEF.

Master this practical approach to reading the medical literature (*No statistics needed!) with expert tips from Dr. Christine Laine, Editor in Chief, Annals of Internal Medicine, and Dr. Darren Taichman, Executive Deputy Editor, Annals of Internal Medicine. They teach us what we should be reading, and detail their thought processes as they appraise an article. Topics covered include: Is 3 minute critical appraisal possible? What’s the deal with P-values? What are common sources of bias? How does the approach differ with clinical trials versus observational studies versus meta-analyses? *Minimal statistics needed ; ) Full show notes available at http://thecurbsiders.com/podcast Join our newsletter mailing list. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Time Stamps 00:00 Intro 01:13 Listener comment on Entresto 02:50 Picks of the week 09:36 Getting to know our guests 14:00 How to stay up on the medical literature 17:15 Three minute critical appraisal 19:15 Step 1: Assess the outcome being studied 20:50 Statistical versus clinical significance 22:33 Evaluating composite endpoints 24:47 Statistical power 28:58 Evaluating for bias 34:40 Recap of what we’ve learned so far 36:33 Is PICO useful? 39:01 Observational studies and bias 41:09 Evaluating a meta-analysis 46:05 Take home points 50:35 The Curbsiders recap the episode 53:02 Outro Tags: literature, appraisal, meta, analysis, analyze, critical, read, medical, journal, study, randomized, observational, systematic, review, clinical, trial, assistant, care, education, doctor, family, foam, foamed, health, hospitalist, hospital, internal, internist, nurse, medicine, medical, primary, physician, resident, student

Update your management of heart failure (HF) with expert tips from Cardiologist Dr. Eric Adler, Associate Professor of Medicine and Director of Cardiac Transplant and Mechanical Circulatory Support at UC San Diego. We cover how to use BNP, a simple way to examine jugular venous distention, medical therapy for heart failure, the PARADIGM-HF trial, and how to use sacubitril/valsartan (Entresto). Full show notes available at http://thecurbsiders.com/podcast Join our newsletter mailing list. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Time Stamps 00:00 Intro 04:25 Rapid fire questions 06:00 Palliative care and heart failure 08:40 Book recommendation 10:20 Advice for teachers and learners 12:27 Clinical case of HF 13:38 Classification and staging of HF 17:07 Discussion of BNP 19:35 How to perform neck vein exam for JVD 21:20 BNP for prognosis 23:00 BNP at hospital discharge 26:36 Factors that affect BNP 27:25 Initial patient counseling 32:35 Exercise in HF 34:00 Additional testing at time of diagnosis 36:28 Initial medical therapy 38:30 Discussion of diuretics and dosing 42:50 Aldosterone antagonists 44:30 PARADIGM-HF and entresto 51:27 Medications to avoid in HF 54:14 Digoxin 57:30 Dr. Adler’s take home points 59:11 Stuart questions dosing conventions 60:48 Outro Tags: arni, assistant, care, diuretics, doctor, education, failure, family, foam, foamed, health, heart, hospitalist, hospital, internal, internist, neprilysin, nurse, management, medicine, medical, physician, practitioner, primary, resident, sacubitril, student

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: AIFA, EMA, Merk, Celgene, PRA Health Sciences, Novartis, Tesaro.Persone: Beatrice Lorenzin (Ministro della Salute), Claudio Vincelli (Generale NAS), Mario Melazzini (AIFA), Alessandra Aloe (Merk, Ssfa), Antonio Messina (Merk), Jean-Yves Chatelan (Celgene), Walter Ricciardi (ISS), Michele D’Alto (AO Monaldi Di Napoli), Leonardo Radicchi (AIPI), Vittorio Vivenzio (AMIP), Carmine Dario Vizza (Università ‘La Sapienza’ di Roma), Michele Senni (Ospedale Papa Giovanni XXIII di Bergamo), Giuseppe Maiocchi (Novartis), Roberto Florenzano (Tesaro).Nuove terapie: alemtuzumab, Entresto, rolapitant, nivolumab.Patologie: obesità, ipertensione polmonare, sclerosi multipla, scompenso cardiaco, nausea e vomito indotti da chemioterapia (CINV), tumore testa-collo a cellule squamose.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: AIFA, EMA, Merk, Celgene, PRA Health Sciences, Novartis, Tesaro.Persone: Beatrice Lorenzin (Ministro della Salute), Claudio Vincelli (Generale NAS), Mario Melazzini (AIFA), Alessandra Aloe (Merk, Ssfa), Antonio Messina (Merk), Jean-Yves Chatelan (Celgene), Walter Ricciardi (ISS), Michele D’Alto (AO Monaldi Di Napoli), Leonardo Radicchi (AIPI), Vittorio Vivenzio (AMIP), Carmine Dario Vizza (Università ‘La Sapienza’ di Roma), Michele Senni (Ospedale Papa Giovanni XXIII di Bergamo), Giuseppe Maiocchi (Novartis), Roberto Florenzano (Tesaro).Nuove terapie: alemtuzumab, Entresto, rolapitant, nivolumab.Patologie: obesità, ipertensione polmonare, sclerosi multipla, scompenso cardiaco, nausea e vomito indotti da chemioterapia (CINV), tumore testa-collo a cellule squamose.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

Pretravel consultation (1:10), sacubitril/valsartan (Entresto) (5:40), intimate partner violence (9:00), flu shot recommendations (13:30), aspirin (14:40), mental status examinations (18:40), and our favorite Tweets (21:30).

One in four heart failure patients are readmitted within 30 days of hospital discharge...often due to medication-related problems. But early follow-up from you...their pharmacist...can help. For example, talking with patients within 2 days of discharge PLUS an office visit within 7 days prevents one ED visit for every 9 heart failure patients...and one readmission for every 52 patients. Expect to see more hospitals, prescribers, and payers looking to work with YOU to help reduce readmissions. Your expertise can improve care...and save money. Think of your role managing heart failure as similar to managing anticoag patients. There'll be professional and financial opportunity in it. Offer comprehensive med reviews to identify and resolve problems. Recommend an ACEI or ARB plus an "evidence-based" beta-blocker...bisoprolol, carvedilol, or metoprolol SUCCINATE...for systolic heart failure. Suggest adding an aldosterone antagonist if symptoms persist. Recommend trying to titrate to target doses that improve survival, such as lisinopril 20 to 40 mg/day or metoprolol succinate 200 mg/day. Consider suggesting Entresto (sacubitril/valsartan) instead of the ACEI or ARB if hospitalization occurs despite use of target doses. But be aware of hypotension, and avoid Entresto when systolic BP < 100 mmHg. Educate patients about self-management...and when to get help. Include caregivers...they are crucially important to success in many cases. Consider using a heart failure questionnaire from our PL Detail-Document to identify red flags BEFORE patients get worse. For example, advise patients to report if weight changes by more than a few pounds. Emphasize adherence with meds, limiting fluids, diet, etc. For example, help patients understand how taking their ACEI or ARB improves their outcomes. Plus this also impacts Star Ratings. Suggest pillboxes or consider offering med sync to boost adherence. Use our PL Conversation Starter to guide your discussions. Communicate with colleagues if you find problems with med lists or identify adherence issues...to prevent gaps in therapy.

BNP use as a lab and therapeutic are discussed. The episode also explores the PARADIGM-HF trial and Neprilysin inhibition. The novel combination medication sacubitril/valsartan (Entresto) for systolic CHF is evaluated in depth. Clinical tips for avoiding angioedema and other clinical pearls are provided.

In this episode, we discuss the new drug class, ARNI, recently approved for heart failure with a focus on sacubatril/valsartan (Entresto) and the PARADIGM-HF trial.

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