Gilead Sciences announced February 12 that NASH is developing drugs.The ASK1 inhibitor selonsertib (GS4997) missed the primary endpoint in its first phase III clinical trial (STELLAR-4).
STELLAR-4 is a phase III randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of the new NASH drug selonsertib in patients with compensated cirrhosis (F4) due to NASH.The trial enrolled 877 patients with NASH-induced compensated cirrhosis and compared the effects of selonsertib and placebo on fibrosis at two doses.
Eligible adults aged 18 to 70 years were randomized to receive selonsertib 18 mg (n = 354), selonsertib 6 mg (n = 351), or placebo (n = 172) for up to 240 weeks; selonsertib or placebo was administered orally once daily.The primary endpoint of the study was a comprehensive assessment of the proportion of patients with less improvement in grade 1 fibrosis (fibrosis improvement ≥ stage 1) according to the NASH CRN classification who did not have worsening NASH at week 48 and achieved event-free survival at week 240.
STELLAR-4 trial results showed that in a study of 877 subjects who received the study drug, there were 14 patients treated with selonsertib 18 mg.4% in patients treated with selonsertib 6 mg.Five percent achieved fibrosis improvement of stage ≥ 1 and NASH did not worsen after 48 weeks of treatment; patients receiving placebo achieved fibrosis improvement of stage ≥ 1 of 12.8%.Selonsertib was generally well tolerated, and safety results were consistent with previous studies.But missed the prespecified 48-week clinical endpoint.
Gilead indicated that further in-depth analysis of the findings is ongoing, that the data will be presented to an upcoming scientific meeting, and that the STELLAR-4 study will be completed in a manner that is in the best interest of each patient, in collaboration with the Data Monitoring Committee and researchers.
"While we are disappointed that the STELLAR-4 study did not meet its primary endpoint, we remain committed to advancing therapy for patients with advanced fibrosis due to NASH, particularly as there is a significant unmet need for effective and well-tolerated therapies in this area."Gilead is also collecting data on compensated cirrhosis due to NASH, including a number of biomarkers, which will further improve understanding of the disease and inform broader NASH development programs," said John McHutchison, MD, Chief Scientific Officer of Gilead, in a news release.
Selonsertib is an ASK1 inhibitor and is a highly selective kinase inhibitor.The full name of ASK1 is apoptosis signal-regulating kinase, which can activate JNK.P38 and other key regulatory proteins induce inflammation and fibrosis.
NASH is a chronic and progressive liver disease characterized by fat accumulation and inflammation in the liver, which can lead to scarring or fibrosis that impairs liver function.Individuals with advanced fibrosis, including bridging fibrosis (F3) or compensated cirrhosis (F4), have a significantly increased risk of liver-related mortality and all-cause mortality.
Gilead is advancing a variety of novel investigational compounds for the treatment of advanced fibrosis caused by NASH, evaluating single agent and combination therapies for NASH-related diseases.ACC2 inhibitor GS-0976 has been acquired in recent years.FXR agonist GS-9674.ASK1 inhibitor selonsertib.LOXL2 inhibitor SIM.At the end of 2018, he bought three exclusive priority acquisitions of TGFbeta antibodies from Scholar Rock.
John McHutchison also said he was looking forward to the results of another phase III STELLAR-3 trial of selonsertib and the phase II ATLAS trial of selonsertib, cilofexor (GS-9674) and firsocostat (GS-0976) in patients with bridging fibrosis (F3).