[Updated 1:49 p.m. ET. See below.] An experimental Gilead Sciences treatment for the severe fatty liver disease NASH failed to beat a placebo in Phase 3 testing—the second time the drug has failed in a late-stage clinical trial.
Gilead (NASDAQ: GILD) developed its drug selonsertib to treat nonalcoholic steatohepatitis, more commonly referred to as NASH, a liver disease that causes inflammation and scarring. When the disease progresses to liver failure, patients require a liver transplant. There are no FDA-approved treatments for NASH.
Selonsertib is a small molecule drug meant to block ASK1, a protein that promotes inflammation, cell death, and the liver scarring known as fibrosis. Foster City, CA-based Gilead tested its drug in two Phase 3 trials. The results announced Thursday came from an 802-patient study called STELLAR-3.
The study’s main goal was improvement in fibrosis scores without worsening of NASH after 48 weeks of treatment, and some patients treated with the drug showed signs of hitting that mark. Gilead reported that 9.3 percent of patients treated with the 18 mg dose of the drug showed improvement in signs of fibrosis. In the group treated with the 6 mg dose, 12.1 percent of patients showed fibrosis improvement. But the placebo group was even better, with 13.2 percent of patients showing better fibrosis scores after 48 weeks.
Selonsertib had previously failed to beat a placebo in a Phase 3 study called STELLAR-4, which tested the drug in patients with more severe cases of NASH. Despite the STELLAR-3 failure, Gilead isn’t giving up on its NASH drug. John McHutchison, Gilead’s chief scientific officer and head of research and development, said in a prepared statement that the company believes NASH treatment will require a combination of different drugs. This combination approach is currently being evaluated in a Phase 2 trial testing selonsertib along with two other experimental Gilead drugs, cilofexor and firsocostat. Data from that study are expected later this year.
[Updated to add paragraph with analyst comment.] In a research note, JMP Securities analyst Liisa Bayko wrote that that the second selonsertib clinical trial failure is probably “the final nail in the coffin” for ASK1 inhibitor drugs for Gilead and others. Watertown, MA-based Enanta Pharmaceuticals (NASDAQ: ENTA) has reported encouraging data for its two preclinical ASK1 drugs. But Bayko said that the company will likely halt that work in light of Gilead’s disappointing data and instead turn its focus to its other NASH programs. She added that selonsertib’s failure is good news for Intercept Pharmaceuticals (NASDAQ: ICPT) of New York, which so far has the only NASH medicine that has demonstrated anti-fibrotic effects.
Meanwhile, Gilead is bolstering its efforts to find additional NASH therapies. Last week, the company inked a three-year deal with AI startup Insitro, which will apply its technology to NASH drug discovery research.