Surfing the MASH Tsunami

S4-E34.2 - Practical and Plausible Notes On Injectables Versus Oral Agents


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This month, Surfing NASH embarks on a series of episodes dedicated to takeaways emerging from June's two major conferences: the 2023 EASL Congress in Vienna and the American Diabetes Association's 83rd Scientific Sessions meeting in San Diego. In doing so, the Big Band of Surfers (Stephen Harrison, Jörn Schattenberg, Louise Campbell and Roger Green) are joined by Mazen Noureddin for a fascinating conversation which covers compelling data and ideas emerging from the drug development space.

Jörn and Mazen begin by prompting Stephen with questions around the FASCINATE-2 study outlined in the previous conversation. Stephen confirms that the data presented was based on a planned interim analysis of a prespecified subset of patients at week 26 of a 52-week trial. Mazen next asks questions designed to challenge Stephen to reveal how excited he truly is about the drug (denifanstat) and surrounding data. Specifically, Mazen asks whether denifanstat feels like an add-on agent when compared to more 'mainstream' FGF-21 agents. Stephen responds by referring to a need for what he characterizes as a plethora of agents before commenting on possible and practical differences between orals and injectables. He suggests that injectables seem to produce faster drops in liver fat reduction and ALT improvements than orals, although orals may 'catch up' over time in a sort of 'tortoise and the hare' phenomenon. From here Stephen describes the ways which he might use injectables first in more severe patients before introducing orals after achieving the desired effect. He also talks about simply starting with orals in less severe patients. The group digs deeper into these ideas by introducing ACC inhibitors and pan-PPAR agonist, lanifibranor, to the conversation. Finally, concluding comments return to the theme that injectables might produce stronger efficacy results, although there are several agents yet to be clearly differentiated among orals.

Each conversation covers a lot of ground on drug development, analysis of trial results, and the upcoming increases in importance of omics and artificial intelligence. If you have questions or comments around the EASL Congress or ADA meetings, or the themes and data discussed in this episode, we kindly ask that you submit reviews wherever you download the discourse. Alternatively, you can write to us directly at [email protected].

Stay Safe and Surf On


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