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Last year, Stephen Harrison expounded on a string of press releases presaging some of the most promising data of the last decade in NASH drug development. As Principal Investigator, he reviewed on the podcast Phase 2b results from Akero’s HARMONY Trial. This is a 24-week study evaluating the efficacy and safety of the FGF-21 agonist efruxifermin (EFX) in patients with clinically relevant NASH (F2-F3). The study met its primary endpoint for both the 50mg and 28mg EFX dose groups. Respectively, 41% and 39% of EFX-treated patients experienced at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24 (compared with 20% for the placebo arm).

Stephen walks through his presentation on Akero’s lead product candidate EFX and two important points emerge. First, Stephen and Sven Francque share the idea that “not all FGF-21’s are created equal.” FGF-21’s themselves need to be stabilized due to their two-hour half-lives. The first FGF-21, pegbelfermin, was PEGylated and revealed significant challenges in clinical development. EFX is a bivalent structure – two molecules stabilized by a fusion protein. This appears to work far better. The conversation continues with more points and questions about the study results and implications. An interesting idea surfaces: EFX might function better as an induction therapy to be followed by an oral maintenance therapy and a long-term monotherapeutic solution. As the session winds down, the group speculate the dynamics of what happens when disease regresses to a point where there is far less liver damage.