Iqirvo reduces fatigue in PBC patients

Additional analyses from the ELATIVE study (LBP-027) suggest that patients with primary biliary cholangitis (PBC) treated with Iqirvo had greater improvements in fatigue compared to placebo after 52 weeks, as measured by both the PROMIS Fatigue Short Form 7a questionnaire (42.9% Iqirvo versus 31.3% placebo) and PBC-40 fatigue domain (22.6% Iqirvo versus 15.4% placebo). Among patients with moderate-to-severe fatigue at baseline, more than twice as many patients treated with Iqirvo (66.7%) achieved clinically meaningful improvements compared to placebo (31.3%). Importantly, the data suggest that the positive effect of Iqirvo on fatigue occurs independently of its effect on pruritus.

These findings are supported by additional late-breaking exploratory data (LBP-025) from a comprehensive proteomic analysis with longitudinal samples from patients in ELATIVE evaluated using Olink technology covering more than 5,500 proteins. Over 20 proteins involved in disease biology mapping to pathways involved in inflammation and immune response, bile acids and lipid homeostasis, fibrosis, and key PBC symptomatic domains, including pruritus and fatigue, had changes in expression in patients treated with Iqirvo with biochemical response at Week 52. Effects observed on fatigue-associated proteomic signatures appeared to be associated with PPARα activation.

“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,” said Dr David Jones, Professor of Liver Immunology for the Faculty of Medical Science at Newcastle University. “As a physician treating people with PBC, these new data are providing important insights into how the action of IQIRVO could impact fatigue.”

“These mechanistic data reinforce the value of IQIRVO as an important treatment option for people with PBC,” said Dr. Sandra Silvestri,  EVP and Chief Medical Officer, Ipsen. “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.”

ELATIVE is a multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial, with an open-label long-term extension (NCT04526665). ELATIVE is evaluating the efficacy and safety of elafibranor 80mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the existing first-line therapy for PBC. The trial enrolled 161 patients who were randomized 2:1 to receive elafibranor 80mg once daily or placebo. Patients with an inadequate response to UDCA would continue to receive UDCA in combination with elafibranor or placebo, while patients unable to tolerate UDCA would receive only elafibranor or placebo. Patients continued their assigned treatment after Week 52 until all patients had completed their treatment or for a maximum of 104 weeks. The open-label long-term extension of ELATIVE remains ongoing.