- Gilead Sciences' lead therapy targeting a fatty liver disease known as NASH has failed a late-stage trial, sending shares of the big biotech down by nearly 5% in early trading Tuesday.
- The trial, named STELLAR 4, tested Gilead's selonsertib in patients with liver fibrosis so severe they developed compensated cirrhosis. Patients were put on either a 6 mg or an 18 mg regimen of selonsertib, or on placebo. Results showed 14.4% of the 18 mg group and 12.5% of the 6 mg group experienced fibrosis improvement of at least one stage as measured by the NASH Clinical Research Network classification.
- Those results, however, weren't significantly better than the 12.8% of placebo-treated patients who also experienced at least one stage of fibrosis improvement. Gilead said analysis of the findings is ongoing and that data will be submitted to an upcoming scientific conference. Another Phase 3 study, STELLAR 3, is testing selonsertib in a less sick patient population and is set to read out in the second quarter.
Selonsertib is one of the few treatments for non-alcoholic steatohepatitis, or NASH, that has made it into late-stage testing. Despite that achievement, Wall Street didn't have high hopes the drug would succeed in STELLAR 4.
That's largely because the trial enrolled NASH patients with F4 fibrosis — the highest level on a widely used fibrosis scale. Analysts noted that not only is fibrosis improvement a hard endpoint to hit, but that selonsertib's efficacy data set thus far has been for patients with less severe liver damage.
"While fibrosis is a dynamic process, it typically does not reverse spontaneously ... and has not been shown to be tractable to pharmacologic intervention in other disease settings," Geoffrey Porges of SVB Leerink wrote in a Jan. 11 investor note.
Porges pointed to scleroderma, a chronic connective tissue disease, and idiopathic pulmonary fibrosis, a lung disease, as other examples of where pharmaceutical companies have had trouble reversing fibrosis.
"All of these diseases have been resistant to many attempts to achieve such outcomes, and the challenges to its achievement in the liver are equally large," he wrote. "Selonsertib is yet another failed attempt at this lofty goal."
Gilead, however, is far from done with its drug.
The late-stage STELLAR 3 study of patients with F3 fibrosis should read out next quarter, according to the company. Gilead also has a Phase 2 study in the works testing three of its drugs —selonsertib, an FXR agonist called cilofexor and an ACC inhibitor called firsocostat — alone and in combination with each other to treat F3 and F4 NASH patients.
Yet with one late-stage failure already in the books, Wall Street analysts largely don't anticipate positive trial results for STELLAR 3.
What some do expect, though, is Gilead to search externally for more NASH candidates to fill its pipeline.
"After speaking with [management], we view this trial failure as likely increasing their appetite for new NASH assets and that they will remain committed to the space, which we believe could cause companies with mid/late-stage NASH assets in development to trade up on the news — though it does also highlight the challenges in current understanding of NASH biology and endpoints," RBC Capital Markets analyst Brian Abrahams wrote in a Feb. 11 note.
Though not mid- to late-stage, Gilead recently put more than $1.5 billion on the table to gain access to fibrosis programs from Scholar Rock, a biotech.
Adding to dealmaking prospects: Gilead's chief financial officer said at the J.P. Morgan Healthcare Conference in early January that M&A is a top focus for capital allocation in 2019.
NASH competitors, including Viking Therapeutics and Madrigal Pharmaceuticals, saw their stocks rise after the STELLAR 4 news.
Next up in the field, however, is Intercept Pharmaceuticals, which expects to soon read out Phase 3 results from its REGENERATE study. The trial tests the biotech's drug obeticholic acid — already approved for another liver disease called primary biliary cholangitis — in NASH patients with stage two or three fibrosis.
Also due to report late-stage results this year is France's Genfit, although data isn't expected until later in the year.