This conversation between Scott Friedman, Laurent Castera, Louise Campbell and Roger Green covers what the panelists found exciting, important or striking about the presentations of clinical trial results at TLM2023.  Instead of focusing immediately on MASH drugs, Scott suggested we should not overlook the idea that elafibranor is preparing to come to market in the US as a novel medication for PBC with good efficacy and safety from patients who do not respond well to ursodiol or obeticholic acid. I note that elafibranor is only one of two PPARs speeding toward market in PBC with exciting data given what we all heard in the late-breaker presentation on seladelpar. Scott also mentions to integrin antagonist from Pliant in PSC, a disease with no available solutions today. Laurent agrees with Scott that the rare disease drug advances were more exciting than the advances in more common liver diseases.

I bring up papers addressing the value of FGF-21 and FGF-19 agents in cirrhosis, which showed some promise for compensated cirrhotic patients. Scott politely disagrees, feeling that while these agents might hold disease steady, they do not address the challenges and mechanisms necessary to meaningfully regress disease. We agree there is a benefit to any agent that slows or reverses the course of disease even slightly in that this buys the patient more time to be treated with more exciting medications still in the pipeline. Scott notes that for Hepatitis C, a far simpler disease it took 25 years from discovery to cure on a path of incremental process. Scott notes that drug development successes are keeping investors interested, which is encouraging in a challenging environment for investment. Laurent returns to the issue of cirrhosis, noting that there are multiple challenges and concomitant bad behaviors like alcohol consumption. He points out that where good studies exist, these are short studies with small samples. Scott points out that MASH is less like hepatitis and more like inflammatory diseases like IBD, where causes of underlying disease are difficult to determine and there is no single pathway in drug development. He buttresses this by noting that in clinical trials, resmetirom provided benefit to only 25% of patients. 

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