It looks like Gilead’s dreams of winning the first-to-market non-alcoholic steatohepatitis (NASH) race are becoming increasingly out-of-reach, following another trial fail.
In April, Gilead announced that one of its key NASH candidates selonsertib, a ASK1 inhibitor, failed a crucial phase 3 test, after the drug was unable to improve fibrosis without worsening of NASH, in those with bridging fibrosis (F3).
Selonsertib had already failed another phase 3 test two months prior, that involved advanced NASH patients (F4) whose disease had progressed into compensated cirrhosis.
Its renewed efforts also seem to have been for naught, after this most recent fail. Gilead had been studying both combination and monotherapy investigational treatments for advanced fibrosis (F3-F4), to no avail.
According to the company, “no regimen led to a statistically significant increase in the proportion of patients who achieved the primary efficacy endpoint of a ≥1-stage improvement in fibrosis without worsening of NASH”.
The phase 2 ATLAS study had been investigating dual combinations and monotherapy regimens of farnesoid X receptor cilofexor (30mg), acetyl-CoA carboxylase inhibitor firsocostat (20mg) and selonsertib (18mg).
As monotherapy treatments, firsocostat and cilofexor were only able to hit the primary endpoint in approximately 12% of patients. The combination regimen of selonsertib and firsocostat reduced scarring in 16% of patients, selonsertib-cilofexor in 19% and firsocostat-cilofexor the most successful at 21%.
“NASH is a complex disease driven by multiple mechanisms. The results from the ATLAS study suggest the potential for a combination therapeutic approach for patients with advanced fibrosis by targeting different aspects of this disease,” said Merdad Parsey, chief medical officer, Gilead Sciences.
“We continue to analyse the ATLAS data and will work with regulators to determine appropriate next steps for these therapies.”
NASH is a type of non-alcoholic fatty liver disease which causes an accumulation of fat in the liver, which in turn leads to chronic inflammation and fibrosis. It is commonly associated with obesity, diabetes and high-cholesterol.
Currently, there are no approved treatments for the condition, and the race to market has proved difficult for big pharma companies.
Also looking to make headway in NASH is Novartis, which recently announced positive data from a phase 2b study of its investigational candidate tropifexor.
Interim analysis from that study demonstrated that higher doses of the drug resulted in improvements across a number of key biomarkers for NASH.
As well as Novartis, other major pharma companies including Pfizer, Allergan, Merck & Co and Bristol-Myers Squibb are pursuing treatments in NASH.