dm+d

Unassigned

New Medicines

Non-alcoholic steatohepatitis (NASH)

Information

New molecular entity
Gilead Sciences
Gilead Sciences

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Jun 19: No longer listed in Gilead pipeline for NASH (PII for diabetic kidney disease); assume development discontinued [6].

Category

An inhibitor of MAP3 kinase 5 (also known as apoptosis signal-regulating kinase 1 [ASK-1]
Fatty liver disease is divided into alcohol-related fatty liver disease, and non-alcoholic fatty liver disease (NAFLD). The only difference between the two is the alcohol. A threshold of <20 g of alcohol per day in women and <30 g in men is usually used to allow a diagnosis of NAFLD. When inflammation is present, this becomes non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. In Europe prevalence of NAFLD is 20-30% and NASH is 5% [1].
Non-alcoholic steatohepatitis (NASH)
Oral

Trial or other data

Apr 19: Topline data show PIII randomised, double-blind, placebo-controlled STELLAR-3 study (n=802) of selonsertib in Bridging Fibrosis (F3) due to NASH showed that it did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH. Pts had been randomised to receive selonsertib 18 mg (n=322), 6mg (n=321) or placebo (n=159) for up to 240 weeks orally once daily. In the study, 9.3% (o=0.42 vs. placebo) of pts treated with selonsertib 18mg and 12.1% (p=0.93 vs. placebo) of pts on selonsertib 6mg compared with 13.2% of pts on placebo achieved a ≥ 1-stage improvement in fibrosis without worsening of NASH after 48 weeks. [5]


Feb 19: Gilead announce that the PIII STELLAR-4 trial (NCT03053063) has not met its pre-specified primary endpoint (≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network (CRN) classification without worsening of NASH after 48 weeks of treatment). Compared to 12.8% on placebo, 14.4% (p=0.56) and 12.5% (p=1.00) respectively of patients taking 18 mg and 6 mg achieved the endpoint. The company await results from the STELLAR-3 trial and a combination trial due later this year [4].


Q1 17: PIII Stellar 3 study (NCT03053050) to evaluate whether selonsertib can cause fibrosis regression and reduce progression to cirrhosis and associated complications in patient with NASH and bridging F3 starts. Patients with NASH and bridging F3 fibrosis will be enrolled. Study is due to complete Q2 19. PIII (NCT03053063) study is also known as Stellar 4 [3].


Feb 17: Gilead Sciences initiates a PIII trial to evaluate the safety and efficacy of selonsertib in patients with compensated cirrhosis, due to NASH (GS-US-384-1944; NCT03053063). Patients achieving ≥ 1-stage improvement in NASH according to the NASH clinical research network classification at 48 weeks and event free survival are week 240, are the defined endpoints of the study. This randomised, double-blind, placebo-controlled trial is enrolling 800 patients in the US [2].

Evidence based evaluations