S5 - E20.5 - Drug Development Highlights From EASL Congress 2024: Denifenstat, SPECIAL and Other Stories

Surfing the MASH Tsunami

Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss some of the other major drug development stories from the EASL Congress 2024, with special focus on denifenstat, ION-224 and TAK-227, and to review the SPECIAL study on bariatric surgery and cirrhosis.
The panelists concur that all three of these agents have potential value in therapy. Naim expresses some concern about how broad denifestat use will be based on its side effect profile. Later in this conversation, Mazen belives that denifenstat has broad potential for use, given that the most prominent side effect, hair thinning, appears transient and readily manageable. He also notes that denifenstat's impressive results were based on Intent to Treat analysis, which is more rigorous.
Naim states his interest in the ION-224 agent based on its mode of action, which is RNA interference. He also discusses SPECIAL, a study he conducted with the bariatric surgery group at Cleveland Clinic. This study, which evaluated patients with cirrhosis at the time of surgery, demonstrated a 72% risk reduction in major adverse liver outcomes over a 10-year period and 80% risk reduction in decompensation.
Jörn discusses a study he presented on TAK-227, a TG2 inhibitor originally developed for celiac disease. Early results here are quite promising and, as Aleksander Krag mentioned in S5 E17, demonstrates exciting potential for collaboration with drug developers for other diseases.
As the conversation ends, Roger asks Mazen and Jörn what they consider likely to be the biggest MASLD stories at the AASLD Liver Congress in November. Mazen selects the Phase 3 ESSENCE study for semaglutide, while Jörn suggests NITs.