Iqirvo® (elafibranor) proves 3-year efficacy and safety in PBC patients, reducing fatigue and pruritus

Ipsen unveiled new data for Iqirvo® (elafibranor 80 mg tablets) based on an interim analysis from the ongoing open-label extension of the Phase III ELATIVE® study at the American Association for the Study of Liver Disease (AASLD) congress. The late-breaking presentations detailed biomarkers of cholestasis, stabilization of liver fibrosis markers, and moderate-to-severe pruritus data for up to three years in patients treated with Iqirvo. Additionally, exploratory endpoints such as fatigue and sleep were assessed using patient-reported outcomes tools.

Dr. Kris Kowdley, Director at The Liver Institute Northwest, Washington, and primary investigator on the ELATIVE study, highlighted the significance of the data: "Over three years, Iqirvo data suggest sustained efficacy and support the safety profile of the medicine. Importantly, when patients tell me they are less impacted by itch and fatigue—that matters to me as a physician." The findings demonstrated Iqirvo's impact on symptoms of pruritus and surrogate markers of fibrosis, which are crucial for individuals living with primary biliary cholangitis (PBC).

Dr. Mark Swain of the University of Calgary, Canada, noted the difficulty in managing fatigue in PBC patients. He emphasized that patients treated with Iqirvo reported improvement in fatigue and sleep across several patient-reported outcome measures.

The open-label extension included 138 patients who had completed the double-blind period of the Phase III ELATIVE® study. This interim analysis was conducted after at least one year of treatment with Iqirvo in the open-label extension, covering up to three years in total. In patients who continuously received Iqirvo for up to 156 weeks, 85% showed a biochemical response, and 39% achieved ALP normalization at week 156. The data suggested stabilization in liver fibrosis markers and sustained improvements in pruritus for patients with moderate or severe pruritus at baseline.

No new safety concerns were observed, and the most common treatment-emergent adverse events, such as abdominal pain, diarrhea, nausea, and vomiting, were consistent with those reported during the double-blind period.

The impact of Iqirvo on fatigue and sleep was further investigated as an exploratory endpoint. Changes in fatigue or sleepiness were reviewed from baseline to week 104, with clinically meaningful improvements observed in patients with moderate-to-severe fatigue or excessive sleepiness at baseline. Improvements were seen in 56% of patients according to the PROMIS Fatigue Short Form 7a, 50% according to the fatigue domain of the PBC-40, and 69% according to the Epworth Sleepiness Scale.

Sandra Silvestri, EVP and Chief Medical Officer at Ipsen, stressed the devastating impact of PBC on patients and their families. She pointed out that the data reinforces the rationale for prescribing Iqirvo, positioning it as the treatment of choice for PBC patients. Ipsen remains committed to supporting the rare liver disease community.

About Primary Biliary Cholangitis (PBC): PBC is a rare, autoimmune, cholestatic liver disease where the buildup of bile and toxins causes irreversible liver fibrosis and bile duct destruction. It affects approximately 100,000 people in the U.S., primarily women. The disease can worsen over time, potentially leading to liver transplant or premature death if not effectively treated. The high symptom burden of PBC significantly impacts daily life.

Iqirvo (elafibranor) is an oral, once-daily peroxisome proliferator-activated receptor (PPAR) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who respond inadequately to UDCA or as monotherapy in those unable to tolerate UDCA. The mechanism is not entirely understood but includes inhibition of bile acid synthesis through activation of PPAR-alpha and PPAR-delta. Iqirvo received Breakthrough Therapy Designation from the FDA in 2019 and obtained accelerated approval in the U.S. in June 2024, conditional approval in the EU in September 2024, and approval in the UK in October 2024. The approvals are contingent on further verification of clinical benefit.

Ipsen acquired the worldwide rights (excluding China, Hong Kong, Taiwan, and Macau) to elafibranor from GENFIT in 2021.