Gilead’s selonsertib fails PhIII in less sick NASH patients — to no one’s surprise

The prospects of Gilead’s top late-stage NASH drug selonsertib grew dim when it kicked off Phase III readouts with a flop. Two months later, the company conceded that a second, much similar trial has also failed.

John McHutchison

STELLAR-3 set out to measure how well selonsertib, an oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), can improve fibrosis without NASH worsening. That’s the same primary endpoint as STELLAR-4, except that STELLAR-3 recruited patients at a slightly earlier stage of disease — with F3, or bridging, fibrosis — compared to the cirrhosis (F4 fibrosis) patients enrolled in the other trial.

At 48 weeks, only 9.3% of patients treated with the 18 mg dose of the drug achieved a 1-stage improvement or more in fibrosis, while the 6 mg arm registered a 12.1% success rate. Both are lower than the 13.2% with placebo, though the p-values were 0.42 and 0.93 respectively.

The failure comes as little surprise — and thus little impact — to skeptics who were quick to write off the program after the earlier Phase III, Baird analysts wrote in a note.

That being said, Gilead could face some degree of reputational harm, given that this represents the closure of their second Phase 3 NASH program to fail miserably (the first of which was simtuzumab). Moving forward, Gilead is expected to announce histology data from their Phase 2 trial of various two drug combinations in NASH by the end of 2019.

Gilead recently came up with some early data to support the combination approach, showing in a proof-of-concept study that cilofexor and firsocostat can induce a significant decline in hepatic fat — a hallmark of the liver disease. On top of that it’s also announced a collaboration with diabetes giant Novo Nordisk, adding semaglutide to form a three-drug regimen.

Don’t think selonsertib is going away, though. In line with its cocktail strategy, Gilead has begun testing the drug in combination with cilofexor and firsocostat.

“While we had hoped for different outcomes from the STELLAR program, we remain focused and committed to developing highly effective treatments for patients living with advanced fibrosis due to NASH,” Gilead head of R&D John McHutchison said in a statement.

He added that the company will work with collaborators like PathAI and insitro to better understand the disease, a yet unmet medical need in hot pursuit by big and small players alike.

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