S5 - E15.3 - MASH Drug Development: Improvement Since 2020 And Issues That Remain

Surfing the MASH Tsunami

This conversation includes two sections: one optimizing efficacy endpoints to reflect clinical practice and a second looking back at what has improved in MASH drug development since 2020.
The first part of this discussion explores the idea that MASH drug development should reflect the clinical use of the target drug. Sven Francque starts by discussing how much larger the drug effect for Rezdiffra looks if we add lack of fibrosis progression to regression in creating the efficacy endpoint. Will Alazawi agrees but notes that the level of other metabolic diseases will also have an impact on how to assess a drug’s performance and that we do not adequately control for this in trials today. Jörn Schattenberg and Will discuss the value and meaning of stabilizing Type 2 diabetes in relevant patients.

Sven points out that the purpose of a clinical trial is different than the goal of clinical practice. Will agrees but wonders whether this might be a reason that some trials fail.

Roger Green shifts the focus of the conversation by asking Jörn Schattenberg what we have learned since the article he co-authored in 2020. Jörn points to two specific areas where the field has improved: greater consistency in reading biopsy results, and a tendency back then to rush agents into clinical trials without sufficient consideration of pre-trial data and even complex Phase 1 or 2a results. Will notes that trials that reported in 2020 were designed in the early or mid-10s, which means they could not take advantage of the innovations described in the 2020 paper. He goes on to point out that the failed trials produced data that provided the foundation for analyses from consortia and other groups. Sven commends the companies that produced this data for "digging deep" into results to find insights.