S3-E48 – Review of Exciting Clinical Trial Press Releases

Review of Exciting Clinical Trial Press Releases
Stephen Harrison and Mazen Noureddin join regulars Jörn Schattenberg, Louise Campbell and Roger Green to review five recent press releases reporting on trial results from Altimmune, Akero, Poxel, Axcella and Intercept. Dubbed a Wow! episode, the panelists explore some of the most exciting and promising data of the last decade in NASH drug development.

A recent string of press releases has presaged some of the most exciting, promising data of the last decade in NASH drug development. In this episode, Stephen Harrison reviews recent press releases from Altimmune, Akero, Poxel, Axcella and Intercept, while Jörn Schattenberg, Louise Campbell, special guest Mazen Noureddin and Roger Green share questions and impressions.

Last month, Altimmune presented its top-line results of a 12 week Phase 1B study of pemvidutide, a GLP-1/glucagon dual receptor agonist. After outlining the study design, Stephen summarizes the positive results of liver fat content reduction. Jörn takes interest in extending the spectrum of GLP-1s by targeting the liver directly with a glucagon agonist. Mazen notes liver fat reduction as disproportionately higher than what is typically seen in a 4.3% weight loss scenario. He expresses optimism that drug’s positive impact on other metabolic parameters suggests a “whole body approach.” The three then contextualize overall weight loss and liver fat content reductions.

The conversation shifts to Phase 2b results from Akero’s HARMONY Trial. HARMONY met its primary endpoint for both the 50mg and 28mg EFX dose groups, with 41% and 39% of EFX-treated patients experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH at week 24, (vs. 20% for the placebo arm). This leads Mazen to ask whether the future must rely on combination therapies. This leads Roger to recall a similar suggestion from Akero Chief Development Officer on a January 2021 episode. Stephen points out that future therapy might look not only at point-in-time combinations but also sequences of induction and maintenance therapies, as with many cancers.
The next set of data comes from DESTINY-1, a paired liver biopsy Phase 2B trial from Poxel. This 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. Roger expresses enthusiasm that introducing multiple modes of action to the market will create the energy and investment to drive a dynamic explosion of education and exploration in Fatty Liver diseases.

The panel continues exploring oral drugs by reviewing positive interim data from the Phase 2b EMMPACT Study by Axcella. They discuss the broad activity of this drug in addition to its well-tolerated profile and safety.

On a less optimistic note, Stephen outlines the Phase 3 results of the REVERSE trial by Intercept. This study focuses on evaluating the safety and efficacy of OCA in patients with compensated cirrhosis and, ultimately, did not meet its primary endpoint.

Dubbed a Wow! episode by the panelists, there are plenty more observations and supporting data points to be explored in this discussion. Surf on for the full report.

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