Gilead says first data on Nimbus NASH candidate are positive

Gilead Sciences has the first proof-of-concept data for its novel drug candidate for nonalcoholic steatohepatitis (NASH) as it tries to rebuild confidence in its R&D pipeline.

This is the first clinical data on GS-0976, which Gilead acquired from Nimbus Therapeutics in a $1.2 billion deal signed last year. Nimbus has already pocketed around half that figure in upfront and milestone payments.

The new data is the first indication that Gilead's investment is on course in the fiercely contested race to bring NASH drugs to market, although the results—presented at the International Liver Congress (ILC) in Amsterdam today—are very preliminary.

The trial was small and open-label—involving just 10 patients—and revealed that GS-0976 was able to block the formation of new fat in the liver (de novo lipogenesis, or DNL) by 29% over the 12-week study period. The drug also achieved a sizable 43% reduction in liver fat by the end of the trial, although the data on liver fibrosis (scarring) was marginal. Using a biomarker for fibrosis (liver stiffness), patients on GS-0976 showed a decline from 3.4 to 3.1 kPa at week 12, which was just barely statistically significant.

NASH is a form of chronic liver disease caused by a buildup of fat in the liver and is thought to affect around 15 million Americans. If left untreated, it can cause scarring, or fibrosis, in the liver, which can eventually lead to liver failure.

Some experts predict it could replace alcoholism and viral hepatitis as the leading cause of liver transplants by the next decade, generating a market for NASH-targeted medicines that could reach a whopping $35 billion at peak.

"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, M.D., of University of Texas Health Science Center, who presented the trial results at the ILC. "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."

GS-0976 is an allosteric acetyl-CoA carboxylase (ACC) inhibitor, an emerging class of drug candidates for NASH and other liver diseases. The drug is in a clutch of trials in healthy volunteers and NASH patients, including a phase 2 trial in 125 NASH patients that is fully recruited and due to report results in the summer.

It's one of three liver fibrosis programs at Gilead alongside FXR agonist GS-9674—originally developed by Phenex and also in phase 2 testing—as well as ASK1 inhibitor selonsertib that is in two phase 3 trials involving NASH patients with fibrosis (STELLAR 3) and cirrhosis (STELLAR 4). Gilead pulled the plug on another NASH hopeful, LOXL2 inhibitor simtuzumab, last year.

Faced with declining sales of its blockbuster hepatitis C franchise—and after a crop of R&D disappointments across multiple indications in recent months—Gilead has been under pressure to use its hefty cash reserves for a major deal.