April 24, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Foster City, Calif.-based Gilead Sciences announced results from a proof-of-concept study of GS-0976 in nonalcoholic steatohepatitis (NASH).
NASH, sometimes called the “silent liver disease,” resembles alcoholic liver disease, but appears in people who drink little or no alcohol. However, it can be quite severe and lead to cirrhosis. According to the National Institute of Diabetes and Digestive and Kidney Diseases, NASH affects 2 to 5 percent of people in the U.S. There are currently no specific treatments aside from weight loss, increased physical activity, and avoiding alcohol and unnecessary medications.
Gilead says 10 patients treated with GS-0976 for 12 weeks showed statistically significant improvements in liver fat content and noninvasive markets of fibrosis.
“The identification of novel strategies for reducing liver fibrosis is a core focus in the development of therapies for patients with NASH,” said Eric Lawitz, lead study author and vice president of Scientific and Research Development, Texas Liver Institute and clinical professor of Medicine, University of Texas Health, San Antonio, in a statement. “We know that elevated DNL is a major contributor to the pathogenesis of NASH and these data suggest that decreasing DNL through inhibition of ACC can lead to significant reductions in both liver fat content and stiffness, with early decreases in markers of liver fibrosis.”
Gilead acquired GS-0976 when it acquired Nimbus Therapeutics in April 2016 for $400 million. In November 2016, Gilead paid Nimbus another $200 million in a milestone payment. There is at least another $600 million in potential milestones waiting.
John Carroll, writing for Endpoints News, says, “This is all music to the ears of the team at Nimbus, which has another $600 million in milestones riding on this pact. It also helps Gilead, which has been castigated by a group of analysts for refusing so far to put its considerable cash cache to work acquiring a biotech or two that can significantly add to its late-stage pipeline.”
Gilead is focusing a lot of its resources on NASH. It is planning or conducting Phase II and Phase III trials of single-agent and combination therapies aimed at several pathways associated with NASH, including metabolic dysregulation, inflammation and fibrosis. Its pipeline includes apoptosis signal-regulating kinase 1 (ASK1) inhibitor, selonsertib; the selective, non-steroidal Farnesoid X receptor (FXR) agonist, GS-9674; and GS-0976, an ACC inhibitor.
There’s a lot of interest in NASH. Dublin-based Allergan has bolstered its efforts in the area with several acquisitions late last year, including San Francisco-based Tobira Therapeutics and Akarna Therapeutics, based in San Diego. Other companies working on NASH therapeutics include Intercept , Genfit , Novo Nordisk , Shire , Novartis (NVS), Galmed and Conatus.
Intercept is generally considered to be closest to the market with a therapy for NASH. Its compound, obeticholic acid (OCA), is an FXR agonist, and is currently in a Phase III trial known as REGENERATE. On February 10, the company provided an interim update that also included changing its endpoints and the definition of NASH improvement. In a conference call with investors, the company’s chief executive officer, Mark Pruzanski, said, “First, we are amending our co-primary endpoint from fibrosis improvement and NASH resolution to fibrosis improvement or NASH resolution. We originally designed REGENERATE to include both primary endpoints based on the FLINT trial results, which showed that OCA treatment resulted in improvement in all key aspects of NASH, notably in fibrosis. While we of course remain confident in demonstrating efficacy on both endpoints, this protocol change effectively gives us two shots on goal.”
Gilead’s GS-9674 is also an FXR agonist. Gilead acquired the compound from Phenex Pharmaceuticals in January 2015.
MedCityNews writes, “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.’”
