Ipsen IQIRVO hits 85% ALP normalisation in Phase III PBC trial
Ipsen has reported late-breaking Phase III data for IQIRVO (elafibranor) in primary biliary cholangitis, with 85.3% of patients achieving normalisation of alkaline phosphatase at Week 52 compared with 23.3% on placebo (p<0.0001). The findings from the ELSPIRE study are being presented at The Liver Meeting 2026, hosted by the American Association for the Study of Liver Diseases, and are simultaneously published in HEPATOLOGY.
The ELSPIRE study enrolled 92 patients across ten countries in a population that has not previously featured in registrational trials for IQIRVO: those with ALP between 1 and 1.67 times the upper limit of normal. This group had historically been considered relatively well controlled, with the 1.67× ULN threshold conventionally defining inadequate treatment response. The trial randomised patients 2:1 to receive IQIRVO 80 mg once daily or placebo.
Trial findings
Beyond the primary endpoint of ALP normalisation, secondary readouts reinforced the topline result. An adjusted mean ALP reduction of 36.5% from baseline was recorded in the IQIRVO arm versus 4.2% with placebo. A total of 84.5% of patients in the active arm also met a composite criterion of ALP normalisation together with a reduction of at least 15% from baseline, against 20.0% in the placebo group. Complete biochemical response, defined as normal levels across total bilirubin, ALP, AST, ALT, albumin and INR, was achieved by 64.3% of IQIRVO patients versus 16.7% on placebo. Reductions in total bilirubin and GGT were also reported. IQIRVO was well tolerated, with most treatment-emergent adverse events rated mild or moderate, no serious events attributed to the drug, and low rates of discontinuation.
Kris V. Kowdley, of the Liver Institute Northwest and Washington State University, said the data "support consideration of normal ALP as an achievable treatment goal for patients with an incomplete response to first-line ursodeoxycholic acid treatment."
Ipsen also presented six-month interim data from the ongoing Phase IV real-world ELFINITY study, which showed clinically meaningful improvements in fatigue and pruritus among patients with moderate-to-severe symptoms at baseline, alongside biochemical response in 57.5% of evaluable patients.
Market context and regulatory path
IQIRVO holds a notable regulatory position in the PBC market. The FDA granted accelerated approval in June 2024, the EMA conditional approval in September 2024, and the MHRA followed in October 2024. Both the US and EU approvals are contingent on further verification of clinical benefit, making datasets such as ELSPIRE material to Ipsen's ongoing regulatory obligations. The company said it is sharing the ELSPIRE data with regulatory authorities.
The PBC treatment landscape has grown more competitive in recent years. Obeticholic acid (Ocaliva, Intercept Pharmaceuticals) and seladelpar (Livdelzi, Gilead Sciences) are among the approved second-line options, with the field increasingly focused on biochemical endpoints that go beyond the traditional 1.67× ULN threshold. ELSPIRE is notable in that it deliberately targeted the lower ALP band, a population that some guidelines have considered adequately managed. If regulatory authorities accept ALP normalisation as a primary treatment goal in this group, it could broaden prescribing criteria for IQIRVO and shift competitive dynamics across the class.
PBC affects approximately 1.8 people per 100,000 annually worldwide, with the majority of patients being women. Progressive disease can lead to cirrhosis, liver failure and the need for transplantation, and published data cited in the release associate ALP above the upper limit of normal with reduced transplant-free survival. Ipsen is also pursuing treatments for progressive familial intrahepatic cholestasis and Alagille syndrome, positioning the company as a rare cholestatic liver disease specialist with a multi-asset strategy in an area of high unmet need.