S3-E43.1 - Combination Agents for Fibrotic Regression

Send us Fan MailThis discussion begins with Naim offering an in-depth look into the mechanics of the recently published combination study. He explains that “semaglutide hits every point” in terms of effects on metabolic syndrome, cardiovascular outcomes, obesity and liver fat, but it has not yet been proven in monotherapy to regress fibrosis. Gilead Sciences had three agents whose potential anti-fibrotic effects the company wanted to explore fully, so Gilead and Novo Nordisk, which owns semaglutide, formed a partnership to develop these drugs.One agent, selonsertib, turned out to be ineffective, but the other two, the FXR agonist cilofexor and the ACC agent firsocostat proved efficacious in combination with semaglutide. Naim goes on to describe the mechanics of the study and presents results demonstrating that even in a six-month trial, the triple therapy proved efficacious with a favorable side effect profile.Jörn notes one very important aspect of combination agents: by requiring lower levels of each individual agent, they have the potential to exhibit superior safety and side effect profiles that a higher-dose monotherapy might.The rest of this conversation features additional comments by Mazen, namely addressing the short duration of the study. He suggests that if extended, the study quite possibly had more positive results to be shown, namely, through further weight loss. Mazen also raises an intriguing prospect with an interesting acknowledgment: this is an open-label study with neither biopsies nor a placebo arm. However, he suggests, this kind of design will become far more prevalent in a future when one agent in the study has already been approved and is widely used with patients.