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A recent string of press releases presaged some of the most exciting, promising data of the last decade in NASH drug development. In this conversation, Stephen Harrison continues his review of Phase 2B results from Akero’s HARMONY Trial before introducing more positive Phase 2B results from a study by Poxel. Mazen Noureddin, Jörn Schattenberg, Louise Campbell and Roger Green share impressions.  

Mazen asked whether the future must rely on combination therapies. The question leads Roger back to a comment Akero Chief Development Officer, Kitty Yale, made in a January 2021 podcast. She stated that Akero believes the future of NASH therapy might not hinge on combination therapies. Stephen suggests it prudent to continue following these results as it might be premature to discuss how this drug will be applied. The uncertainty stems from questions around the drug’s modes of action and delivery, potential for tolerability issues or possible reduction of effect over time. Roger asks whether this drug, like BMS’s pegbelfermin, might wear off over time. Stephen suggests that differences in the chemical structure of these two FGF-21 agents points that EFX might not do so. He explains how a drug like EFX could serve as induction therapy followed by a lower cost, better tolerated oral agent. 

The conversation shifts to the next set of data produced by Poxel. The DESTINY-1 study reports positive histology results for PXL065, a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone. Stephen elucidates on the science of this drug and the mechanics of deuterium as a stabilizer. The study design consists of 117 subjects across four cohorts: three different doses versus placebo. The trial met its primary efficacy endpoint for liver fat content reduction at 36 weeks for all doses. Louise emphasizes the positives associated with delivering an oral mechanism.