- Intercept Pharmaceuticals on Thursday unveiled full data from a Phase 3 trial of Ocaliva in non-alcoholic steatohepatitis, or NASH, that revealed few surprises but continued to throw a spotlight on side effects, particularly the nearly one out of 10 patients who stopped taking the pill due to itching.
- At the same European medical meeting where Intercept was touting Ocaliva, Gilead Sciences released promising Phase 2 data of a combination treatment that did not cause itching, bouncing back from the disappointment from the failure of a more advanced NASH project.
- The two companies are among many trying to fight for a share of a market that could number more than 20 million patients in the U.S. While Ocaliva could arrive first, any competitor with similar effectiveness and fewer side effects could still steal significant market share.
Intercept is in the enviable position of leading in a heated competition to get the first NASH treatment to the market.
The New York-based biotech has an even greater advantage in that its candidate, Ocaliva (obeticholic acid), is already marketed for another liver disease called primary biliary cholangitis. Nonetheless, the drug's side effect profile appears a drawback as a treatment for NASH, a condition in which fat accumulates in the liver and can lead to fibrosis and cirrhosis.
Itching and elevations in low-density lipoprotein (LDL), or "bad cholesterol," have been known since the data from a National Institutes of Health trial called FLINT were unveiled in 2014, and confirmed when Intercept revealed top-line data from the latest trial, called REGENERATE, in February.
The full data release at the European Association for the Study of the Liver meeting in Vienna, Austria, lent no more confidence that Ocaliva would be the best NASH drug should commercial competition emerge.
The main finding is important for patients hoping to stop the disease from progressing. Data showed 23.1% of patients taking a 25 mg daily dose of Ocaliva saw their liver fibrosis scores improve by one stage or more after 18 months of treatment, significantly more than the 11.9% of placebo patients who reached the same outcome.
However, that finding must be balanced against the 51% of patients taking that dose of Ocaliva who experienced pruritis, or itching, symptoms. Nine percent of the patients taking the 25 milligram daily dose stopped taking Ocaliva because of itching.
LDL elevations, meanwhile, reached 22.6 mg per deciliter over baseline after four weeks, but fell to just 4 mg per deciliter over baseline at 18 months. Half of all patients, placebo and Ocaliva alike, were on lipid-lowering therapies at baseline, most of which were statins. An additional 20% were prescribed statins during the course of the trial to manage LDL elevations.
In addition, 3% of the patients taking 25 mg dose experienced gallstones, compared with less than 1% of placebo patients, which puts those Ocaliva patients at risk of undergoing surgery.
In the competitive field of NASH, Intercept's numbers looked even less positive when compared to emerging data from Gilead.
The California biotech reported data from a combination of two phase 2 agents, cilofexor and firsocostat, that generated reductions in liver enzyme levels similar to what Ocaliva did in the Flint trial. Notably, however, those reductions came without increasing pruritis.
The Gilead combination resulted in a median 37% reduction in alanine aminotransferase (ALT) and a median 32% reduction in gamma-glutamyl transpeptidase (GGT). In the Flint trial Ocaliva reduces ALT 38% and GGT 37%.
Gilead's combination is years behind Ocaliva, of course, and the California-based group has already fumbled on NASH development when its lead project selonsertib failed to beat placebo in an early Phase 3 trial.
Those considerations didn't appear to placate investors in Intercept, who sent shares in the biotech down 13% today.
RBC analyst Brian Abrahams, however, chalked it up to "sell the news" behavior by investors who had bid up shares ahead of the data release.