Iqirvo (Elafibranor) Shows Sustained Efficacy and Safety in Long-Term PBC Treatment
核心洞察
Interim data from the open-label extension of the Phase III ELATIVE trial demonstrate Iqirvo's sustained efficacy and safety profile for up to three years in patients with primary biliary cholangitis (搜索) (PBC).
Patients treated with Iqirvo experienced improvements in pruritus and stabilization of surrogate markers of liver fibrosis, suggesting a positive impact on disease progression.
Exploratory endpoints revealed that Iqirvo led to improvements in fatigue and sleep, as reported by patients, highlighting its potential to address key symptoms of PBC.
Ipsen's Iqirvo® (elafibranor) has demonstrated sustained efficacy and a consistent safety profile for up to three years in patients with primary biliary cholangitis (搜索) (PBC), according to interim data from the open-label extension (OLE) of the Phase III ELATIVE® study. These findings, presented at the American Association for the Study of Liver Disease (AASLD) congress, suggest that elafibranor could offer long-term benefits for individuals living with this rare cholestatic liver disease.
Sustained Efficacy and Safety Profile
The 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 promising results. In a subset of patients (n=13) who received continuous Iqirvo treatment for three years, 85% (n=11/13) 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% (n=5/13) achieved ALP normalization.
"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," said Dr. Kris Kowdley, Director at The Liver Institute Northwest, Washington and a primary investigator on the ELATIVE study.
Impact on Liver Fibrosis and Pruritus
Surrogate markers of liver fibrosis, including liver stiffness measurements (n=23) and enhanced liver fibrosis (ELF™) scores (n=19), indicated stabilization from baseline to week 130. Patients with moderate or severe pruritus at baseline (n=5) experienced sustained improvements in this debilitating symptom with continuous Iqirvo treatment for up to 156 weeks.
Improvements in Fatigue and Sleep
Exploratory endpoints focused on fatigue and sleep, common and challenging symptoms in PBC, were also evaluated. At week 104, patients treated with Iqirvo showed improvements in fatigue and sleep across three patient-reported outcome (PRO) tools. Clinically meaningful improvements were observed in 56% of patients with moderate-to-severe fatigue or excessive sleepiness at baseline, according to the PRO Measurement Information System (PROMIS) Fatigue Short Form 7a. Similar improvements were seen in 50% of patients based on the fatigue domain of the PBC-40 and in 69% of patients according to the Epworth Sleepiness Scale (ESS).
"Fatigue is a symptom often reported by people living with PBC and is also very challenging to manage," said Dr. Mark Swain, Department of Medicine, Cumming School of Medicine, University of Calgary, Canada. "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 observations. The most common treatment-emergent adverse events (>10%) reported in the double-blind period of the trial (abdominal pain, diarrhea, nausea, and vomiting) were also reported in the OLE. No new safety signals were identified.
About Iqirvo (elafibranor)
Iqirvo (elafibranor) is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR (搜索)) agonist indicated for the treatment of primary biliary cholangitis (搜索) (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. It was granted 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. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. A confirmatory study of Iqirvo is ongoing (NCT06016842).