While a Phase 2 trial powers on, Gilead Sciences has announced some earlier proof-of-concept data for its investigational acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, in patients with non-alcoholic steatohepatitis (NASH).
The results were presented at the 2017 International Liver Congress now underway in Amsterdam.
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It’s an early win for a drug Gilead acquired from Nimbus Therapeutics in April 2016. A handful of other preclinical programs were included in the deal, which saw Gilead pay an upfront $400 million. A further $200 million was paid out last November, as part of an $800 million pool of potential milestone payments.
Approximately five percent (15.9 million) of Americans are believed to have non-alcoholic steatohepatitis (NASH), but that’s just the tip of the iceberg. It comes as a progression of non-alcoholic fatty liver disease (NAFLD), which affects an estimated 75-100 million Americans.
As an inhibitor of ACC, GS-0976 is designed to interfere with the production of new lipids within the liver and stimulate their breakdown. Based on animal models of fatty liver, ACC inhibition reduces hepatic fat content, inflammation, and fibrosis (scarring), all of which drive the progression of NASH.
Announced Friday, the new data come from an open-label study of 10 patients. A 20 mg oral dose of GS-0976 was taken once daily for 12 weeks. At week 12, Gilead states that patients receiving GS-0976 experienced a 43 percent median relative decrease in liver fat content. Median liver stiffness, a noninvasive marker of fibrosis declined from 3.4 to 3.1 kPa.
According to the company statement, liver biochemistry and serum markers of fibrosis and apoptosis also improved in patients that experienced a reduction in hepatic fat, supporting the biological activity of GS-0976. Only minor Grade 1 or 2 side effects were reported and all participants completed their course of medication.
A separate Phase 2, randomized, double-blind, placebo-controlled trial evaluating GS-0976 in 125 patients with NASH is ongoing.
Based in Foster City, California, Gilead has two other clinical programs in NASH. The most advanced is selonsertib (GS-4997), an apoptosis signal-regulating kinase 1 (ASK1) inhibitor that is now in Phase 3 trials. Selonsertib treats fibrosis associated with NASH.
The third candidate is a selective, non-steroidal farnesoid X receptor (FXR) agonist dubbed GS-9674. It was acquired from Phenex Pharmaceuticals in January 2015, in a deal valued at $470 million. According to Gilead’s website, it is currently in Phase 2 trials.
While difficult, NASH is a natural evolution for Gilead, which made billions pioneering some of the first therapeutic cures for hepatitis C. That market is now saturated, prompting investors to ask “what’s next?”
NASH could be the blockbuster opportunity on the horizon. A 2014 Deutsche Bank industry report titled “NASH — the next big global epidemic in 10 years?” estimated that the market could peak at $30-40 billion by 2025. But it’s not exactly a sitting duck. Startups and Big Pharma alike are pouring into the field with nine-figure acquisitions, prompting a so-called “Dash to NASH.”
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