Intercept hikes NASH hopes with Ocaliva subgroup results. But what about safety?

With more detailed efficacy data from 25-mg Ocaliva, Jefferies analyst Michael Yee thinks the liver toxicity problem on the Intercept drug's use in NASH is largely "overblown." (Michael Bonert/CC BY-SA 3.0)

Still hoping to take Ocaliva into the fatty liver disease field—where no drug has yet been approved—Intercept has resorted to a post hoc analysis to highlight the drug’s efficacy. And it seems the presentation successfully shifted focus away from Ocaliva's safety profile, according to one analyst.

In nonalcoholic steatohepatitis (NASH) patients, a 25-mg dose of Ocaliva achieved a 2-stage or greater liver fibrosis improvement in about three times as many patients patients (13.3% vs. 4.5%) compared with a dummy drug, the New York company reported on Thursday at the European Association for the Study of the Liver (EASL) annual meeting in Vienna. The result falls largely in line with the 23.1% versus 11.9% margin Intercept previously announced for at least 1 stage of improvement.

With its data in hand, Intercept's on track to put Ocaliva up for FDA review in NASH, a blockbuster field that's squarely in the sights of Gilead Sciences, Genfit and others, as evidenced by a host of presentations at the EASL meeting. Ocaliva could win a NASH approval next year, analysts say, and Evaluate's peak sales estimate stands at $2 billion.

When the top-line data were released in February, market watchers zeroed in on Ocaliva's safety risks, namely liver toxicity, an increase in bad cholesterol, and pruritus (itchy skin). But according to Jefferies analyst Michael Yee, doctors “did not ask any question of concern” during Intercept’s presentation at the conference.

“Importantly no questions were even asked on liver tox/safety or Hy’s law [an algorithm to evaluate drug-induced liver injury] or any of those Wall Street concerns,” Yee said in a Thursday note to investors.

When Intercept announced those top-line results, there wasn’t much doubt about Ocaliva’s efficacy, but analysts worried whether the size of the drug's benefit warranted its liver safety risks. A passing increase in LDL cholesterol and dose-related pruritus cases didn’t help, either. And although the 25mg drug was clearly more effective than the 10mg option, it also came with the most safety concerns.

RELATED: With positive phase 3, Intercept to file NASH drug for approval while Inventiva faces a setback

More trial patients on the 25mg dose suffered liver problems but “with no pattern attributable to [Ocaliva],” and serious cases were less than 1% in each of the three arms, Intercept said. LDL increases peaked at 4 weeks, gradually declining to only a 4-point rise above baseline by the 18-month mark. And according to Cantor Fitzgerald analysts, who surveyed influential physicians about the issue, “the vast majority of doctors are comfortable prescribing a statin to their NASH patients (as tolerated) if necessary for an effective NASH therapy.”

Over half of patients on the 25mg dose experienced pruritus, the highest among all three groups. In its Thursday statement, Intercept reiterated that the vast majority of itching problems were mild to moderate. Some 9% of 25mg patients stopped taking their medication because of the itching, compared with less than 1% of patients in the placebo and 10mg groups.

In a Wednesday note before the new Intercept data was unveiled, Cantor analysts argued that more details on itching could be a key differentiator for Ocaliva’s uptake from a commercial perspective. “If a meaningful portion of the pruritus were mild vs. moderate, we think this would be a significant commercial advantage and would minimize real-world dropout rates,” they said.

RELATED: Gilead posts combo NASH data from biotech buyouts

There were of course still some questions about pruritus and statin use during Intercept's Q&A session, but as Jefferies’ Yee sees it, the key is still liver toxicity. For that, he doesn’t see any hurdles “and hence this is mostly overblown and drug should be filed and approved with no major issues in 2020.”

Besides, Intercept also posted more detailed efficacy data to consolidate its case. These included three-fold more patients in the 25mg group whose fibrosis improved rather than worsened, while placebo had no obvious difference. The drug also helped improve some key features of NASH, including hepatocellular ballooning and lobular inflammation, as well as some biochemistry metrics.

Analysts polled by EvaluatePharma figure Ocaliva could reach sales of $2 billion by 2024. But still, nothing is certain until the FDA review, and a final approval—if it comes—might limit the drug’s use in more-specified populations.