FDA Grants Accelerated Approval for Elafibranor as Treatment of Primary Biliary Cholangitis

Updated June 12, 2024, at 11:28 am

The FDA has granted accelerated approval to elafibranor (Iqirvo; GENFIT, Ipsen), a first-in-class, once daily oral peroxisome proliferator-activated receptor (PPAR) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid for those with an inadequate response to ursodeoxycholic acid or as a monotherapy for those who are unable to tolerate ursodeoxycholic acid. The indication is approved under accelerated approval due to reductions in alkaline phosphatase, according to a news release.¹

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"We took elafibranor (Iqirvo) all the way from drug discovery to the end of phase 3 and now, thanks to our partnership with Ipsen, it will be made available to health care providers in the [United States] and ultimately provide patients with a valuable therapeutic alternative,” Pascal Prigent, CEO of GENFIT, said in the news release.¹

Ursodeoxycholic acid is the only approved first-line therapy for those with PBC; however, up to 40% of patients have inadequate response to the treatment, according to authors of a study published in the New England Journal of Medicine. Elafibranor has been shown to decrease the toxic effects of bile acid and inflammation by targeting PPAR-α and PPAR-δ. Investigators aimed to conduct a phase 2 trial to determine the efficacy and safety of elafibranor for patients.²

In the study, individuals aged 18 to 75 years old were included in the trial if they received a diagnosis of PBC and had inadequate repones or unacceptable adverse events with ursodeoxycholic acid from 82 sites in 14 countries. All individuals included had an alkaline phosphatase level at least 1.67 times greater than the upper limit of the normal range and total bilirubin level of no more than 2 times the upper limit of the normal range, according to the investigators. Treatment was randomized in a 2:1 ratio, with individuals receiving once daily elafibranor at a dose of 80 mg to the placebo.²

The primary end point included biochemical response at week 52, defined as an alkaline phosphatase level of less than 1.57 times with a reduction of 15% or more from baseline and the total bilirubin at or below the upper limit of normal range. Key secondary end points included the normalization of the alkaline phosphatase level at week 52 as well as the change in pruritus intensity from baseline through week 52 and week 24, according to the study authors.²

There was a total of 161 patients randomly assigned to receive elafibranor (108 patients) or the placebo (53 patients). The baseline characteristics were similar between the 2 groups, with 96% of patients being women and a mean age of 57 years. The mean baseline alkaline phosphatase level was 321.9 U per liter. Investigators found that a biochemical response was observed in 51% of patients taking elafibranor compared with 4% for the placebo. The response occurred approximately 4 weeks after treatment initiation and was maintained through 52 weeks.²

Normalization of alkaline phosphatase level at week 52 occurred in approximately 15% of patients taking elafibranor and 0% taking the placebo and was consistently higher in the elafibranor group through the 52 weeks compared with the placebo.²

Investigators reported that adverse events (AEs) occurred in more than 10% of individuals receiving elafibranor, including abdominal pain, diarrhea, nausea, and vomiting. The majority of AEs were mild to moderate in severity, according to the study authors.²

According to the news release, the improvement in survival or prevention of liver decompensation have not been demonstrated, and continued approval may be contingent upon verification of clinical benefits in trials.¹

Reference

1. GENFIT: historic milestone achieved with US FDA accelerated approval of Ipsen's Iqirvo for primary bilary cholangitis. News release. GENFIT. June 10, 2024. Accessed June 12, 2024. https://ir.genfit.com/news-releases/news-release-details/genfit-historic-milestone-achieved-us-fda-accelerated-approval

2. Kowdley KV, Bowlus CL, Levy C, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med. 2024;390(9):795-805. doi:10.1056/NEJMoa2306185