S4-34.1 – The Excitement of FASN Inhibitors: Positive 2B Interim Data for Denifanstat

S4-34.1 - The Excitement of FASN Inhibitors: Positive 2B Interim Data for Denifanstat
Stephen Harrison, Mazen Noureddin, Jörn Schattenberg, Louise Campbell and Roger Green unpack compelling drug development stories from this month's EASL Congress and ADA meetings. This session details positive Phase 2b FASCINATE-2 clinical trial interim data for FASN inhibitor, denifanstat.

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.

This is the second session focusing on drug development, and specifically, on several presentations for exciting drugs in development. 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 plenty of compelling clinical trial data.

Jörn preludes this discussion by noting just how much important drug development research was released at this year’s EASL Congress. Stephen proceeds from here to detail positive Phase 2b FASCINATE-2 clinical trial interim data for fatty acid synthase (FASN) inhibitor, denifanstat, as presented at EASL Congress by Rohit Loomba. In the process, Stephen elucidates why the idea of a FASN inhibitor is so exciting. It blocks de novo lipogenesis, which means it can have effects on inflammation and possibly direct fibrosis inhibition. Previously in Season 4, Episode 32, it was discussed why inflammation, which is tied to liver volume, might be a critical component to better understand for therapuetic development and the wider scope of liver health. From here, Stephen goes on to describe the trial, starting with basic design and sharing the MRI-PDFF and biomarker data that was presented at the EASL Congress. He finishes with safety and efficacy data and a general comment that the trial demonstrated, ‘the drug is doing what it’s intended.’

The following excerpt is from the Sagiment Biosciences press release on this topic:

The Phase 2b FASCINATE-2 study is a 52-week randomized, double-blind, placebo-controlled trial evaluating the safety and histological impact of a 50mg daily oral dose of denifanstat compared to placebo in 168 biopsy-confirmed NASH patients with moderate-to-severe fibrosis (stage F2 or F3). The primary efficacy endpoint is histological (liver biopsy) improvement at week 52 in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) without worsening of fibrosis or resolution of steatohepatitis without worsening of fibrosis. Secondary endpoints include biomarkers of inflammation, fibrosis and liver injury.

Denifanstat was well-tolerated and met primary endpoint in planned interim readout with 67% of treated patients achieving ≥30% reductions in liver fat at week 26 compared to 18% placebo (p<0.001) as assessed by MRI-PDFF Denifanstat statistically significantly decreased LDL cholesterol in treated patients and improvements in the circulating blood lipid profile were observed Topline week 52 liver biopsy results expected in the first quarter of 2024 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 questions@SurfingNASH.com. Stay Safe and Surf On

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