14. Selonsertib

Gilead's selonsertib failed two late-stage clinical trials, STELLAR-3 and STELLAR-4, in NASH. (Gilead Sciences)

nonalcoholic steatohepatitis
Sponsor: Gilead Sciences

Gilead Sciences’ ASK1 inhibitor selonsertib was viewed as a front-runner in the challenging nonalcoholic steatohepatitis (NASH) category until it hit a wall this year, missing the mark in a pair of phase 3 trials that spelled the end of the program.

Selonsertib was one of three NASH drugs in Gilead’s clinical pipeline, included in the hope that it could help reduce fibrosis—or scarring—in patients with the fatty liver disease. The STELLAR-4 data dropped in February and showed it was no better than placebo at improving fibrosis in patients with compensated cirrhosis due to NASH.

That was followed in April by the STELLAR-3 readout, in which selonsertib did worse than placebo at reducing scarring in patients with bridging fibrosis—also called stage 3 fibrosis—resulting from NASH. Some analysts said the result wasn’t a surprise given a lackluster showing in phase 2.

Gilead has two other clinical-stage NASH assets in its pipeline, namely FXR agonist cilofexor and ACC inhibitor firsocostat, which are both in midstage testing. Now, however, it faces the prospect of being leapfrogged by at least one of its rivals, although NASH is a tough target and has claimed a number of other candidates in the last few years—including Gilead’s own simtuzumab in 2016.

So far just one new therapy—Intercept Pharma’s obeticholic acid—has shown activity in trials, although it has some safety concerns including severe itching in some patients. The drug is already sold for primary biliary cholangitis as Ocaliva and has been filed for approval in NASH with an FDA decision due next year. EvaluatePharma has a peak sales estimate for the drug that stands at $2 billion, assuming it gets a green light in NASH.

Gilead insists it will learn from the failed STELLAR trials—for example by developing new diagnostics for NASH that could improve trials—and will try to press ahead with its other candidates. It has said it thinks the key to treating NASH effectively lies in drug combinations, and it will have a clearer view of the path forward when the ATLAS combination trial reads out in the coming weeks.

Meanwhile, it continues to add to its R&D programs in this area, such as a recent $1 billion deal with Insitro, including $15 million upfront, to create disease models of NASH and discover targets that affect the progression or regression of the disease.

14. Selonsertib