Ipsen reported positive Phase IIIb ELSPIRE results showing IQIRVO (elafibranor) achieved ALP normalization in 85% of primary biliary cholangitis patients versus 23% with placebo, supporting potential regulatory expansion.
Written By: Mayuresh Salvi, PharmD
Reviewed By: Pharmacally Editorial Team
Ipsen has reported positive topline results from the Phase IIIb ELSPIRE trial evaluating IQIRVO® (elafibranor) in adults with primary biliary cholangitis (PBC) who had an alkaline phosphatase (ALP) level between 1.0 and 1.67 times the upper limit of normal despite treatment with ursodeoxycholic acid (UDCA) or who were unable to tolerate UDCA. The study met its primary endpoint, with 85% of patients receiving IQIRVO achieving ALP normalization at Week 52 compared with 23% in the placebo group (p≤0.0001). The therapy maintained a safety profile consistent with previous studies, with no new safety signals identified.
The findings expand clinical evidence supporting IQIRVO in patients with earlier biochemical disease activity and may substantially broaden the population eligible for treatment if supported by regulatory authorities. Ipsen plans to present the complete data at a forthcoming medical meeting and submit the results to regulatory agencies.
IQIRVO Targets Multiple Pathways Driving Cholestatic Liver Disease
IQIRVO (elafibranor) is an oral, once-daily dual peroxisome proliferator-activated receptor (PPAR)-α/δ agonist. Activation of these receptors reduces bile acid toxicity, improves bile acid transport and detoxification, and helps decrease cholestasis. The drug also exerts anti-inflammatory, anti-fibrotic, and metabolic effects that may slow disease progression in PBC.
Primary biliary cholangitis is a chronic autoimmune liver disease characterized by progressive destruction of the bile ducts. Persistent cholestasis leads to liver fibrosis, cirrhosis, liver failure, and, in advanced cases, liver transplantation. Although UDCA remains the standard first-line therapy, many patients fail to achieve adequate biochemical control, highlighting the need for additional treatment options.
ELSPIRE Demonstrated Significant Improvement in ALP Normalization
The Phase IIIb ELSPIRE trial (NCT06383403) was a randomized, double-blind, placebo-controlled study conducted across 10 countries. The trial enrolled 92 adults with PBC whose ALP remained between 1.0 and 1.67 times the upper limit of normal despite inadequate response or intolerance to UDCA.
Participants were randomized in a 2:1 ratio to receive IQIRVO 80 mg once daily (n=62) or placebo (n=30). The primary endpoint evaluated the proportion of patients achieving ALP normalization after 52 weeks of treatment.
IQIRVO met the primary endpoint with a statistically significant improvement over placebo. According to Ipsen, achieving normal ALP levels is increasingly recognized as an important treatment goal because it is associated with improved long-term prognosis and slower disease progression in PBC.
The overall safety findings aligned with the established safety profile of IQIRVO, and investigators reported no new safety concerns during the study.
Experts Highlight the Importance of Achieving Normal ALP Levels
Kris Kowdley, MD, Director of Liver Institute Northwest and Professor at Washington State University, said growing clinical evidence suggests that maintaining normal serum ALP is associated with the most favorable outcomes for patients with PBC. He noted that the ELSPIRE findings demonstrate that ALP normalization is an achievable treatment goal and could translate into improved long-term prognosis.
Christelle Huguet, PhD, Executive Vice President and Head of Research and Development at Ipsen, said the results strengthen the growing body of evidence supporting IQIRVO and reinforce ALP normalization as a clinically meaningful objective that may help delay disease progression and reduce the need for liver transplantation.
Regulatory Path Forward
IQIRVO received U.S. FDA accelerated approval in June 2024, followed by conditional approval in the European Union in September 2024 and UK approval in October 2024 for adults with PBC who have an inadequate response to UDCA or who cannot tolerate the therapy. These approvals remain contingent on confirmation of clinical benefit.
Ipsen intends to present the full ELSPIRE data at an upcoming scientific congress and submit the findings to regulatory authorities. If accepted, the results could support expanding the use of IQIRVO to patients with lower ALP levels, potentially increasing the number of individuals eligible for treatment.
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About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.