STELLAR-3 phase III study of GS 4997 fails to meet endpoint in NASH

Gilead Sciences announced that STELLAR-3, a Phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of GS 4997 (selonsertib), an investigational, once daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), for patients with bridging fibrosis (F3) due to nonalcoholic steatohepatitis (NASH), did not meet the pre-specified week 48 primary endpoint of an at least 1-stage histologic improvement in fibrosis without worsening of NASH. In the study of 802 enrolled and dosed patients, 9.3 percent of patients treated with selonsertib 18 mg (p=0.42 versus placebo) and 12.1 percent of patients treated with selonsertib 6 mg (p=0.93) achieved an at least 1-stage improvement in fibrosis according to the NASH Clinical Research Network (CRN) classification without worsening of NASH after 48 weeks of treatment, versus 13.2 percent with placebo.

Selonsertib was generally well tolerated and safety results were consistent with prior studies. Gilead will now work with the Data Monitoring Committee and investigators to conclude the STELLAR-3 study in a manner consistent with the best interests of each patient.

Comment: Reported in February 2019, another trial, STELLAR-4, a Phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, did not meet the pre-specified week 48 primary endpoint of a greater than 1-stage histologic improvement in fibrosis without worsening of NASH in patients with compensated cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH). The company is now relying on data from the Phase II ATLAS combination trial of selonsertib, cilofexor and firsocostat in patients with advanced fibrosis due to NASH, which will be available later this year.