S5 - E20.1 - Drug Development Highlights From EASL Congress 2024: Resmetirom

Surfing the MASH Tsunami

Naim Alkhouri and Mazen Noureddin join Jörn Schattenberg and Roger Green to discuss some of the new research on resmetirom at the EASL Congress 2024.
Mazen begins this discussion by covering a paper he presented on Stephen's behalf, looking at dose-response with resmetirom. The analysis indicated that PDFF and histology improvements at the 100mg dose were greater than at the 80mg dose. Mazen speculates that the higher dose might provide a greater anti-fibrotic response as well, although, in a world where biopsy is not required for prescribing, he doubts the study will ever be done. Jörn notes that the most important element of the study might be a demonstration of effect lasting at least 36 months.
As an aside, Mazen mentions a study from Samer Gawrieh demonstrating that dropping liver stiffness to <10kPa correlates with a 75% reduction in clinical liver events. He reports that resmetirom was a bit higher than 10 in Year 1, but dropped below for those patients continuing to Years 2 and 3.
At this point, Naim shifts slightly to compare modes of analysis: Completer Analysis vs. Intent to Treat.
His point is that Intent to Treat, which scores all non-completers as failures, will produce lower rates of response than a "completer" or "modified Intent to Treat" analysis, which either eliminates non-completers or assigns placebo-level response to them.