S6 E8.3 - Deep Dive into Drug Development IV: Other Modes Of Action; Metabolic vs. Pleiotropic Effects

Send us a text

This conversation is the fourth and final segment of SurfingMASH’s April discussion of drug development in memory of Stephen A. Harrison. In addition to co-hosts Jörn Schattenberg, Louise Campbell and Roger Green, panelists include hepatologist and key opinion leader Sven Francque.

The discussion focuses on PPARs, genetic medicines, and other emerging drug classes while considering the idea that drug therapies can have an impact on the liver independent of their effect on fibrosis regression. It begins with Sven discussing his experience as a lead investigator in clinical trials for the pan-PPAR agonist lanifibranor, whose Phase 3 trial is now fully recruited. Sven states that in addition to fibrosis regression, lanifibranor is likely to exhibit other pleiotropic effects, and notes that vascular changes start early in the fibrotic progression process.

After Sven elaborates on these effects, Louise asks about the SCD-1 agent Aramchol. This leads to a discussion about the idea that over time, therapy will probably come to incorporate two separate modes of action, with one to treat the metabolic dysfunction and the other to treat specific effects in the liver or, as Jörn puts it, "combining weight-neutral and weight-reducing drugs." This evolves into a discussion of what Louise terms "personal-centric" medicine, or what patient advocate Mike Betel has previously described on SurfingMASH as "tailored medicine."

The rest of the conversation predominantly lists other classes of drugs, "safe" mitochondrial uncouplers, genetic medicines, and others. Roger inquires about the FASN inhibitors, which are entering Phase 3 clinical trials. Jörn says that the data appears positive and unique. That said, he and Sven agree we need more data.

Louise sounds the closing note for this roundtable by discussing our co-founder, Stephen Harrison, and the energy and enthusiasm he brought to the entire drug development process. The group agrees that Stephen's impact continues to be felt through the MASLD community, even as he is missed by us all.