Elafibranor Achieves 85% ALP Normalization in Phase 3b ELSPIRE Trial for PBC

Elafibranor (Iqirvo) achieved alkaline phosphatase (ALP) normalization in 85% of patients with primary biliary cholangitis (PBC), significantly outperforming placebo (23%; P <.0001) at week 52 in the phase 3b ELSPIRE trial among patients with an inadequate response or intolerance to first-line ursodeoxycholic acid (UDCA).

In a statement, Ipsen announced the trial met its primary endpoint in adults with PBC and baseline ALP levels between 1 and 1.67 times the upper limit of normal (ULN). Investigators also reported a safety profile consistent with previous studies of elafibranor, with no new safety signals identified.

"We now recognize that patients who maintain normal serum ALP have the best outcomes in PBC; therefore, our treatment goals are evolving to aim for ALP normalization as the optimal treatment target for this progressive and chronic liver disease," said Kris Kowdley, MD, Director of Liver Institute Northwest, Medical Director and Senior Scientific Advisor at Velocity Clinical Research, and Professor at Elson S. Floyd College of Medicine at Washington State University, in a statement. "These data from the ELSPIRE trial show that ALP normalization is an achievable goal for patients with PBC and will hopefully improve the prognosis for people living with PBC."

ALP Normalization Emerges as an Important Treatment Goal

ALP normalization has become an increasingly important therapeutic target in PBC, as patients who achieve normal ALP levels have demonstrated better long-term clinical outcomes than those with persistently elevated levels. Rather than focusing solely on reducing ALP, investigators are increasingly evaluating complete biochemical normalization as a marker associated with improved prognosis and slower disease progression.

By enrolling patients with baseline ALP levels between 1 and 1.67 times the ULN, ELSPIRE evaluated whether patients with more modest biochemical elevations could achieve complete ALP normalization, expanding on prior studies of elafibranor in patients with higher baseline ALP levels.

Phase 3b ELSPIRE Met Its Primary Endpoint

Elafibranor is an oral, once-daily dual peroxisome proliferator-activated receptor (PPAR)-α/δ agonist that reduces bile toxicity by modulating bile acid synthesis and detoxification while exerting anti-inflammatory, anticholestatic, antifibrotic, and metabolic effects.

ELSPIRE is a randomized, double-blind, placebo-controlled, 2-arm phase 3b trial evaluating elafibranor 80 mg once daily in adults with PBC who had an inadequate response or intolerance to UDCA. The primary endpoint was the proportion of patients achieving ALP normalization at week 52.

The study enrolled 92 patients across 10 countries with baseline ALP levels between 1 and 1.67 times the ULN and randomized them in a 2:1 ratio to receive elafibranor once daily (n = 62) or placebo (n = 30).

Ipsen reported ALP normalization was achieved in 85% of patients receiving elafibranor compared with 23% of those receiving placebo (P <.0001). The company also noted the safety profile was consistent with previous studies of elafibranor, with no new safety signals identified.

Elafibranor Continues to Demonstrate Consistent Safety

"Normalizing ALP is not just a biochemical outcome, but a tangible objective to delay the need for a liver transplant and improve prognosis for PBC patients," said Christelle Huguet, PhD, executive vice president and head of research and development at Ipsen, in the release. "These results contribute to the growing body of evidence on the potential of IQIRVO to help people achieve ALP normalization."

Ipsen indicated it plans to present the full ELSPIRE findings at an upcoming medical meeting and submit the data to regulatory authorities.

References

1. IPSEN. (2026, July 13). IQIRVO® demonstrates statistically significant improvement in ALP normalization in patients with PBC in Phase IIIb ELSPIRE study. Global. https://www.ipsen.com/press-release/iqirvo-demonstrates-statistically-significant-improvement-in-alp-normalization-in-patients-with-pbc-in-phase-iiib-elspire-study-3325891

2. Murillo Perez CF, Harms MH, Lindor KD, et al; GLOBAL PBC Study Group. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Am J Gastroenterol. 2020;115(7):1066-1074. doi:10.14309/AJG.0000000000000557.