Surfing the MASH Tsunami

S6 - E5 - Drug Development Week: FGF-21s, Cirrhosis, Resmiterom, Gene Therapies


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00:00:00 - Surf's Up: Season 6 Episode 5

Host Roger Green briefly describes this episode’s three sections and introduces Roundtable guests. The Roundtable panel shares groundbreakers. 

00:10:39 - Roundtable: A Deep Dive Into Drug Development, Part One

The opening portion of this month's roundtable centers around two issues: exciting data for FGF-21s and, more generally, treating patients with cirrhosis. Naim Alkhouri sets the tone in his opening comments, which start by focusing on the exciting SYMMETRY data from efruxifermin and then hones in on FGF-21s and resmetirom in cirrhosis. The rest of the conversation features Jörn Schattenberg, Sven Francque and Naim discussing therapies in development for compensated and decompensating cirrhosis.

00;24:44 - Newsmaker: Naga Chalasani on Real-World Experience Prescribing Resmetirom

Naga joins Roger to discuss the paper Early Experience with resmetirom to treat Metabolic Dysfunction-Associated Steatohepatitis With Fibrosis in a Real-World Setting from his group at Indiana University, which his group authored and Hepatology Communications recently posted. The paper, based on IU Health's experience with its first 113 resmetirom patients, shares the group's practical experience developing processes to work closely with the specialty pharmacies dispensing resmetirom and, finally, concludes that a more engaged patient management strategy might reduce drug discontinuation to a level comparable with clinical trials.  

00:47:21 - Expert: Scott Friedman on Gene Therapy, Diversity of Stellate Cell Types, Other Basic Liver Science

Scott and Roger cover a range of basis science topics in a fast-moving 19-minute discussion. It starts with Scott discussing the increasing acceptance that gene therapy is an acceptable way to treat a range of liver diseases, many of which are orphan or ultra-orphan but, in fact, include potential gene therapies for non-cirrhotic MASH and MASH cirrhosis. He notes that in addition to classic gene therapy, which introduces protective gene variants into the systems of patients with the risky variants, gene therapy is now looking to introduce FGF-21 into patients through genetic modification. From there, the conversation covers CAR-T therapy, the increasing ability to identify many different types of stellate cells and the idea that the most effective therapy for eary fibrosis, advanced fibrosis and cirrhosis might require fundamentally different kinds of interventions. The two final elements are the idea that what we now call "MASH" may be several diseases with different etiologies with similar manifestations and a passionate call for all of us to support maintaining NIH funding in whatever ways we can.

01:06:45 - Business Report

As Roger copes with his laryngitis, AI voices deliver an abbreviated business report 

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