Ipsen's Iqirvo (elafibranor) has demonstrated sustained efficacy and a consistent safety profile over three years in patients with primary biliary cholangitis (PBC), according to interim data from the open-label extension of the Phase III ELATIVE study. These findings, presented at the American Association for the Study of Liver Disease (AASLD) congress, suggest that Iqirvo can provide long-term benefits in managing PBC, a chronic cholestatic liver disease. The drug, already approved in the U.S., E.U., and U.K., offers a novel treatment option for patients who have an inadequate response to or cannot tolerate ursodeoxycholic acid (UDCA).
Sustained Efficacy and Safety Profile
The open-label extension (OLE) included 138 patients who had completed the double-blind phase of the ELATIVE study. An interim analysis, conducted after at least one year of Iqirvo treatment in the OLE (up to three years total), revealed that in patients receiving continuous Iqirvo treatment for three years (n=13), 85% achieved a biochemical response, defined as ALP <1.67 x ULN with ≥15% reduction from baseline and total bilirubin ≤ ULN, at week 156. Furthermore, 39% of these patients achieved ALP normalization. These results indicate a sustained therapeutic effect of Iqirvo in reducing key biomarkers of cholestasis.
Impact on Fibrosis and Pruritus
Surrogate markers of liver fibrosis, including liver stiffness measurements (n=23) and enhanced liver fibrosis (ELF™) scores (n=19), suggested stabilization from baseline to week 130 in patients treated with Iqirvo. Additionally, patients with moderate to severe pruritus at baseline (n=5) experienced sustained improvements in this debilitating symptom over the 156-week period. Dr. Kris Kowdley, Director at The Liver Institute Northwest, Washington, emphasized the clinical significance of these findings, stating, "Treatment with Iqirvo had an impact on symptoms of pruritus and surrogate markers of fibrosis, which are important findings for people living with PBC."
Improvements in Fatigue and Sleep
Exploratory endpoints focused on fatigue and sleep, common and challenging symptoms in PBC patients, were also evaluated. Changes in fatigue and sleepiness were assessed from baseline to week 104 using patient-reported outcome (PRO) tools (n=48). Clinically meaningful improvements were observed in patients with moderate-to-severe fatigue or excessive sleepiness at baseline. Specifically, 56% (n=18) of patients showed improvement according to the PRO Measurement Information System (PROMIS) Fatigue Short Form 7a, 50% (n=24) according to the fatigue domain of the PBC-40, and 69% (n=16) according to the Epworth Sleepiness Scale (ESS). Dr. Mark Swain, Department of Medicine, Cumming School of Medicine, University of Calgary, Canada, noted, "Patients treated with Iqirvo reported improvement in fatigue and sleep, across several patient-reported outcome measures."
Safety Profile
The safety profile of Iqirvo remained consistent with previous findings. No new safety concerns were identified during the open-label extension. The most common treatment-emergent adverse events (>10%), which were more frequent in Iqirvo-treated patients during the double-blind period (abdominal pain, diarrhea, nausea, and vomiting), were also reported in the OLE.
Ongoing Research and Regulatory Status
Iqirvo (elafibranor) is a peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Approvals by the FDA and EMA are contingent on further verification of clinical benefit, which is being investigated in an ongoing confirmatory study (NCT06016842).
