Ipsen and GENFIT have shared encouraging top line data from the pivotal ELATIVE Phase III trial evaluating the efficacy and safety of elafibranor, an investigational dual α,δ PPAR agonist, for the treatment of primary biliary cholangitis (PBC).
PBC is a rare cholestatic liver disease in which the bile ducts in the liver are gradually damaged, leading to complications like cirrhosis and liver failure.
The trial met its primary composite endpoint, demonstrating significant patients achieving a clinically meaningful cholestasis response compared to the placebo. Specifically, 51% of patients receiving elafibranor 80mg achieved a cholestasis response, while only 4% of patients on placebo achieved the same response. The cholestasis response was defined as alkaline phosphatase (ALP) levels <1.67 x upper limit of normal (ULN), an ALP decrease of at least 15%, and total bilirubin (TB) levels ≤ ULN at 52 weeks. These ALP and bilirubin level improvements indicate reduced cholestatic injury and improved liver function.
The trial also met its first secondary endpoint, normalization of the ALP at Week 52, with statistically significant improvements for elafibranor compared to placebo. Although there was a trend for pruritus improvement, with a more substantial decrease from baseline in the PBC Worst Itch NRS score for patients on elafibranor, this difference did not reach statistical significance. Elafibranor was tolerated well, and its safety profile was consistent with previously reported studies.
PBC is a progressive autoimmune liver disease predominantly affecting middle-aged women and significantly impacts patients' quality of life. Existing therapies, such as ursodeoxycholic acid (UDCA), are ineffective for all patients, leaving a high unmet medical need.
Based on the positive results from the ELATIVE trial, Ipsen intends to pursue regulatory applications for elafibranor after discussions with the FDA and EMA.
ELATIVE, a multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial, included 161 patients with PBC who had an inadequate response or intolerance to UDCA. The trial was designed to determine the efficacy of elafibranor 80mg once daily compared to placebo.
Patients with an inadequate response to UDCA continued to receive a combination of UDCA with elafibranor or placebo, while patients unable to tolerate UDCA received only elafibranor or placebo. The study also featured an open-label long-term extension.