• Gilead’s most advanced drug for non-alcoholic steatohepatitis, a fatty liver disease better known as NASH, has failed a second late-stage clinical trial, arguably costing the big biotech a leading position in the field.
• The latest setback for Gilead’s selonsertib came Thursday, with the release of topline data from the STELLAR 3 study showing a higher percentage of patients in the placebo arm versus two experimental arms achieved fibrosis improvement without NASH worsening, as measured by criteria from the NASH Clinical Research Network.
• STELLAR 3 enrolled 802 patients with a more advanced stage of liver fibrosis, classified as F3 or bridging fibrosis. Gilead earlier this year announced selonsertib failed a different Phase 3 trial that tested it in patients with F4 fibrosis — which is the most severe stage, characterized by the development of compensated cirrhosis.

Gilead is part of a small group of drugmakers with late-stage NASH assets. But misfires in the STELLAR program have dimmed the prospects of selonsertib coming to market anytime soon, at least as a monotherapy.

In STELLAR 3, for instance, investigators found that after 48 weeks of treatment, just 9% of patients receiving the higher selonsertib dose and 12% receiving the lower dose hit the study’s co-primary endpoint of achieving a one-stage or greater improvement in fibrosis without NASH worsening. The study’s placebo group, meanwhile, saw 13% of patients succeed on that endpoint.

Results weren’t much better in the STELLAR 4 study.

Gilead isn’t giving up on the drug entirely, but will trim back selonsertib’s clinical ambitions given the late-stage failure.

The company has an ongoing Phase 2 program called ATLAS that is evaluating the drug both as a monotherapy and in a variety of combinations. A data readout is slated for the fourth quarter.

However, a Gilead spokesperson noted in an email to BioPharma Dive the selonsertib monotherapy arm in ATLAS will be discontinued, but that the combo arms will not be changed.

While Gilead continues to grow its NASH pipeline through R&D collaborations and buyouts, the fact remains that selonsertib’s failure as a monotherapy means the company will have a longer wait to break into the potentially lucrative market. Cantor Fitzgerald analyst Alethia Young predicts it will be three to four years before Gilead starts seeing commercial NASH revenue.

Gilead could ramp up that timeline, though, should it pursue M&A. Young wrote in an April 25 investor note that with more than $30 billion in cash on its balance sheet, Gilead could buy “one or many late-stage NASH assets.” Currently, Intercept Pharmaceuticals is the only company with positive late-stage data for a NASH therapy, but other mid- to late-stage readouts from rival drugmakers should trickle in over the next few years.

“We believe Gilead should be a leader in NASH with its existing liver disease sales force, which we believe could be one of the best in the industry,” Young wrote in her investor note.