S6 - E5.1 - FGF-21s and A Promising Future on Cirrhosis

Send us Fan MailThis conversation is the opening segment of SurfingMASH's April discussion, in memory of Stephen A. Harrison, on drug development. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include hepatologists and key opinion leaders Sven Francque and Naim Alkhouri. This opening discussion focuses on exciting advances in one drug class (FGF-21s) and, more broadly, on exploring ways to treat cirrhosis. As Naim points out in his opening comment, these two issues— cirrhosis as a challenge and FGF-21s as a possible solution path —intersect in clear and exciting ways. He notes that the FGF-21 efruxifermin has been reported to have significant improvement in patients with cirrhosis, while the FGF-21 pegozafermin has shared positive results in a small cohort of patients. He also notes that a third FGF-21, efimosfermin alfa, has results in advanced non-cirrhotic MASH that suggest potential for similar efficacy in patients with cirrhosis, but this must be studied and confirmed in clinical trials. He mentions that resmetirom may also be showing signs of efficacy in some patients with cirrhosis. The entire package, he says, is a "game changer."Jörn notes that we are having parallel advances in treatment for advanced, non-cirrhotic patients. Sven concurs and comments that we are seeing effects that are not strictly related to metabolic disease. There is exceptional power that we can demonstrate one-level regression in sicker patients. The three agree that, at the same time, we are seeing cirrhosis trials that will lead to outcomes data; outcomes trials in non-cirrhotic medications may not be far away.Roger asks whether we are making progress in treating patients living with decompensated cirrhosis. Sven discusses what we are learning about treating portal hypertension, which is an important benefit unrelated to fibrosis regression. Simply improving portal hypertension will have an impact on endpoints. Naim points out that some ongoing trials include patients with cirrhosis, including survodutide and belapectin. Louise notes it will require "great P.R." to reverse some of the current perceptions about cirrhosis, but that this is "great." Naim states that even today, we have "a lot to offer" patients with portal hypertension or other symptoms of decompensation. As he concludes, he notes that this is underappreciated today.