Gilead’s chances of winning the first-to-market nonalcoholic steatohepatitis (NASH) race has dwindled after one of its key candidates selonsertib failed in a crucial phase 3 test.
During the STELLAR-3 trial, the apoptosis signal-regulating kinase 1 (ASK1) inhibitor failed to meet its primary endpoint, which was to improve fibrosis without worsening of NASH in those with bridging fibrosis (F3).
Gilead was hit with very similar news two months ago, where selonsertib failed another phase 3 test, STELLAR-4, that involved advanced NASH patients (F4) whose disease progressed into compensated cirrhosis.
Analysts already had low expectations for the drug to make much of an impact in F4group, primarily because the drug’s main mechanism of action is to tackle inflammation and fat deposition rather than fibrosis, the main marker in F4 patients.
However, analysts remained hopeful that the drug could demonstrate better results in the F3 subgroup, but during the 802 patient enrolled study, only 9.3% of those treated with selonsertib at 18mg, and 12.1% of those treated with the drug at 6mg, achieved the endpoint.
This was compared to the placebo group, which saw 13.2% of patients achieve the same result.
“While we had hoped for different outcomes from the STELLAR programme, we remain focused and committed to developing highly effective treatments for patients living with advanced fibrosis due to NASH,” said John McHutchison, chief scientific officer and head of research and development, Gilead.
McHutchinson said the company will continue to work with the STELLAR data and its external collaborators, such as PathAI and insitro, to further its understanding of this complex disease.
Gilead isn’t calling it quits on the drug just yet, highlighting its phase 2 ATLAS trial, which involves testing selonsertib in a regimen made up of cilofexor and firsocostat in patients with advanced fibrosis due to NASH.
That data will be available later this year, and McHutchison said Gilead now believes that an effective therapy for NASH will “ultimately require a combination approach”.
Although the setback is disappointing for Gilead, the California, US-based drugmaker has other assets in its pipeline for NASH, mostly due to various acquisitions over the years, including Arresto, Pfenex and Nimbus Apollo.
A number of other major pharma players such as Pfizer, Novartis, Allergan, Merck & Co and BMS are pursuing a treatment for NASH however, making Gilead far from alone in trying to bring a candidate to market.
The company seen as closest to this goal is Intercept, which recently presented further data backing up its case for Ocaliva in NASH.
Three times as many patients on the higher 25mg dose of Ocaliva in the REGENERATE study saw an improvement of two stages or more in their liver fibrosis compared to placebo (13.3% versus 4.5%).
However, the results were far from a home run, as Ocaliva missed a co-primary endpoint of resolving NASH, and more than half of patients on the 25mg dose experience pruritus (severe itching of the skin) to the point where 9% had to abandon treatment.