Iqirvo Shows Significant Fatigue Improvement in Patients with Primary Biliary Cholangitis After 52 Weeks in Phase III ELATIVE Trial

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Updated data from the pivotal Phase III ELATIVE trial (NCT04526665) show Iqirvo (elafibranor) significantly improved fatigue in patients with primary biliary cholangitis (PBC) after 52 weeks.^1,2 The updated trial results, presented at the European Association for the Study of the Liver congress, demonstrated that these treatment effects were independent of pruritus and bolstered by mechanistic proteomic analyses from the trial, according to the investigators.

“For so many patients living with PBC, fatigue is a debilitating symptom that can impact their ability to perform daily tasks or participate in social activities,” David Jones, MD, PhD, professor of Liver Immunology for the Faculty of Medical Science at Newcastle University, said in a press release. “As a physician treating people with PBC, these new data are providing important insights into how the action of Iqirvo could impact fatigue.”¹

Iqirvo is an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist. The drug has been found to reduce the toxic effects of bile acid and inflammation via downstream modulation of PPAR-α and PPAR-δ.³

Iqirvo was granted accelerated approval by the FDA in June 2024 for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) for patients who had an inadequate response to UDCA or as a monotherapy for patients unable to tolerate UDCA. The approval was based on results from the ELATIVE trial also published by The New England Journal of Medicine.^3,4

Trial Design

The multi-center, randomized, double-blind, placebo-controlled ELATIVE trial analyzed the efficacy and safety of Iqirvo at a dose of 80 mg administered once daily compared to placebo in patients with PBC who an inadequate response or intolerance to UDCA. Investigators randomly assigned 161 patients in a 2:1 ratio to receive Iqirvo or placebo. Those who showed an inadequate response to UDCA continued to receive it in combination with Iqirvo or placebo, whereas those unable to tolerate UDCA were administered Iqirvo monotherapy or placebo.

Patients stayed on the assigned therapeutic regimen after 52 weeks until all patients in the trial completed treatment or for a maximum of 104 weeks. The trial’s open-label, long-term extension is ongoing.

The ELATIVE trial’s primary endpoint was a biochemical response at week 52. Key secondary endpoints included normalization of alkaline phosphatase level at week 52 and change in pruritus intensity from baseline through week 52 and through week 24, as per the Worst Itch Numeric Rating Scale.

Trial findings released in 2023 show 51% of patients administered Iqirvo achieved a biochemical response compared to 4% in the placebo cohort. Alkaline phosphatase levels were normalized in 15% of patients administered Iqirvo compared to none in the placebo cohort at week 52.³

Latest results show that patients administered Iqirvo achieved greater improvements in fatigue versus placebo after 52 weeks. These results were determined by the PROMIS Fatigue Short Form 7a questionnaire, at 42.9% in the Iqirvo cohort compared to 31.3% in the placebo cohort, and the PBC-40 fatigue domain, at 22.6% in the Iqirvo cohort compared to 15.4% with placebo.¹

Among patients with moderate-to-severe fatigue at baseline, 66.7% in the Iqirvo cohort achieved clinically meaningful improvements compared to 31.3% in the placebo cohort. According to the investigators, these data indicate that Iqirvo’s efficacy in improving fatigue is independent of its effect on pruritus.

“These mechanistic data reinforce the value of Iqirvo as an important treatment option for people with PBC,” Sandra Silvestri, MD, Ipsen EVP and chief medical officer, said in a press release. “Today, we have a clearer understanding of the molecular pathway implicated in PBC. We believe the more we learn about a disease, the more effective we can be in developing treatments for patients that address both the disease and debilitating symptoms.”¹

References

1. Late-breaking exploratory data highlights the impact of IQIRVO® (elafibranor) on fatigue and provides mechanistic insights into anti-inflammatory and symptom-related effects in patients with primary biliary cholangitis. News release. Ipsen. May 7, 2025. Accessed May 8, 2025. https://www.ipsen.com/press-releases/late-breaking-exploratory-data-highlights-the-impact-of-iqirvo-elafibranor-on-fatigue-and-provides-mechanistic-insights-into-anti-inflammatory-and-symptom-related-effects-in-patients-with-prim-3075746/

2. Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) (ELATIVE). ClinicalTrials.gov. Updated April 30, 2025. Accessed May 8, 2025. https://clinicaltrials.gov/study/NCT04526665

3. 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

4. GENFIT: historic milestone achieved with US FDA accelerated approval of Ipsen's Iqirvo for primary bilary cholangitis. News release. GENFIT. June 10, 2024. Accessed May 8, 2025. https://ir.genfit.com/news-releases/news-release-details/genfit-historic-milestone-achieved-us-fda-accelerated-approval