Ipsen, Genfit report phase 3 rare liver disease success, setting up showdown with Intercept

Ipsen and Genfit are coming for Intercept Pharmaceuticals. With their phase 3 rare disease trial hitting its primary endpoint, the partners plan to seek U.S. and European approvals of elafibranor, their rival to Intercept’s Ocaliva.

Elafibranor is the dual peroxisome activated receptor agonist that was, at one point, a front-runner in the race for the nonalcoholic steatohepatitis (NASH) market. Weak data eliminated the NASH opportunity, but Genfit kept going after the rare liver disease primary biliary cholangitis (PBC). In 2021, the French biotech persuaded its compatriot Ipsen to pay 120 million euros ($131 million) to partner on the project. 

Now, the companies have reported phase 3 data in the indication. The study met its primary endpoint, with 51% of patients on the 80-mg dose of elafibranor achieving the required response compared to 4% of people in the placebo group.

The primary endpoint was a composite of three measures related to an enzyme that is elevated in PBC patients and a liver damage biomarker. Intercept used the same composite endpoint in its phase 3 trial. In that study, 46% of patients in the Ocaliva titration arm met (PDF) the endpoint compared to 10% of people in the placebo group.

Genfit has identified pruritus, the medical term for severe itching, as an area in which it may have an edge over Ocaliva. Pruritus is a common symptom in patients with PBC and Ocaliva appears to exacerbate it, with 56% of patients in the titration arm of the phase 3 trial reporting the adverse event compared to 38% of people in the placebo group.

In the elafibranor trial, Ipsen and Genfit saw “a trend” for improvement, “with a greater decrease from baseline in the PBC Worst Itch NRS score for patients on elafibranor compared to placebo.” The change fell short of statistical significance but may still give the partners an angle of attack as they try to wrestle the PBC market from Intercept.

The market represents scraps compared to the blockbuster NASH opportunity that Genfit and Intercept looked poised to compete for a few years ago. Going into 2020, Intercept was preparing for an advisory committee and Genfit was closing in on phase 3 data. Things unraveled after that. Elafibranor failed in the phase 3 NASH trial, and Intercept finally abandoned its pursuit of the disease last week.  

Now, the rivalry has turned to PBC. Intercept, having won approval in 2016, generated $285.7 million in U.S. Ocaliva sales last year. Ipsen and Genfit are preparing to file for an FDA approval that would position them to start competing with the Intercept drug.