Spread the love

 

Following the announcement on February 12 that the ASK1 inhibitor selonsertib (GS4997) missed the first-order endpoint in its first phase III clinical trial (STELLAR-4), Gilead announced on April 25 that selonsertib was in another STELLAR-3 study. The scheduled clinical endpoint of 48 weeks was not reached.

 

STELLAR-4 study

STELLAR-4 is a phase III randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) caused by NASH. A total of 877 NASH-induced compensatory cirrhosis patients were enrolled, and the effects of selonsertib and placebo on fibrosis were compared between the two dose groups.

Eligible adults aged 18 to 70 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 a day. The primary endpoint of the study was a comprehensive assessment of the proportion of patients with no improvement in grade 1 fibrosis (fibrosis improvement ≥1) in patients who did not have NASH deterioration at week 48 and who achieved event-free survival at week 240 according to the NASH CRN classification. .

The results showed that after 48 weeks of treatment, the percentage of patients with no improvement in NASH in the selonsertib 18 mg treatment group and 14.4% in patients with fibrosis improvement ≥1, 12.5% ​​in the selonsertib 6 mg treatment group, and 12.8% in the placebo group. Selonsertib is generally well tolerated and the safety results are consistent with previous studies. However, the pre-set 48-week clinical endpoint was missed.

 

STELLAR-3 study

The STELLAR-3 study was a phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with NASH-induced bridging fibrosis (F3). A total of 802 patients were enrolled in the trial, with elonsertib 18 mg (n=322), selonsertib 6 mg (n=321) or placebo (n=159) administered once daily for 240 weeks.

The primary end point of the study was a comprehensive assessment of the proportion of patients with no improvement in grade 1 fibrosis (fibrosis improvement ≥1) in patients who did not have NASH deterioration at week 48 and who achieved event-free survival at week 240 according to the NASH CRN classification.

The results showed that after 48 weeks of treatment, the rate of NASH in the elonsertib 18 mg treatment group did not worsen and the proportion of patients with at least grade 1 fibrosis improved was 9.3%, 12.1% in the elonsertib 6 mg group, and 13.2% in the placebo group.

NASH is a chronic and progressive liver disease characterized by accumulation of fat 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 compensatory cirrhosis (F4), have a significantly increased risk of liver-related mortality and all-cause mortality. The full name of ASK1 is an apoptosis signal-regulating kinase that activates key regulatory proteins such as JNK and P38 to induce inflammation and fibrosis. Selonsertib is an ASK1 inhibitor and is a highly selective kinase inhibitor.

On April 13th, Gilead just reached a cooperation with Novo Nordisk in the field of NASH to explore the effect of somalupin combined with cilofexor and firsocostat in the treatment of NASH. The two companies will also jointly conduct preclinical exploration studies to improve understanding of the pathology of NASH.

Leave a Reply

Your email address will not be published. Required fields are marked *