Gilead rocked by phase 3 failure of selonsertib in NASH

A phase 3 trial of Gilead’s NASH prospect selonsertib has bombed. The ASK1 inhibitor was no better than placebo at improving fibrosis, wiping out hopes that selonsertib would spearhead Gilead’s push into a new market.

Gilead moved selonsertib into phase 3 on the back of a midphase program that left big questions about the efficacy of the drug unanswered, notably because the key study was relatively small, short and lacked a placebo arm. The doubts created by the shortcomings of the phase 2 study and the data it generated have now proven to be well founded.

For the phase 3 STELLAR-4 trial, Gilead enrolled close to 900 patients and randomized them to receive one of two doses of selonsertib or placebo once a day. After 48 weeks, Gilead checked how many participants had experienced a 1-stage or more histological improvement in fibrosis without worsening of NASH.

Of the 354 patients who took the higher dose of selonsertib, 14.4% experienced such improvement. That compared to 12.8% in the placebo arm and 12.5% in the lower-dose cohort, meaning neither dose statistically outperformed the control and the lower dose fared worse numerically. The finding was damning enough for Gilead to start wrapping up the trial, which was scheduled to run for up 240 weeks.

The data wiped 4% off Gilead’s stock in after-hours trading, and was down 3.2% premarket on Tuesday morning, despite several analysts seeing the flop as unsurprising given doubts raised by the phase 2. Gilead could still revive selonsertib with positive data from an ongoing phase 3 in earlier-stage patients and a phase 2 combination study. But the data from STELLAR-4 have further dampened expectations ahead of those upcoming readouts.

If selonsertib proves to be a total bust, it will join a growing list of assets that were once heralded as a way for Gilead to unlock new revenue streams but ultimately failed deep in the clinic. Gilead pulled the plug on another NASH prospect, simtuzumab, in 2016 and has seen eleclazine, momelotinib and other drugs intended to move it deeper into fields such as cardiovascular disease and cancer flame out. 

Gilead has other NASH assets in its pipeline but now faces the prospect of coming to market well after the frontrunners. Intercept Pharmaceuticals has taken Gilead’s place at the front of the race and is due to deliver data from its own phase 3 by the end of the quarter. 

Shares in Intercept climbed 2% in after-market trading as investors focused on the removal of a potential competitor, not concerns that Gilead’s failure may be a negative signal for the NASH field as a whole. Jefferies analyst Michael Yee shared the view that differences between Gilead and Intercept’s drugs mean the STELLAR-4 findings are no cause for alarm.

“We do not believe STELLAR-4 data today has any read-through to [Intercept] phase 3 data in Q1, given [Intercept’s] OCA is a different mechanism (FXR) that has shown much more robust positive data in its phase 2 study. If this study works and is clean, that asset would be much more scarce and valuable given [Gilead] was actually viewed as a possible competitive threat,” Yee wrote in a note to investors.