Understanding Elafibranor (Iqirvo) for PBC: Insight From New Clinical Trials

In June, elafibranor (Iqirvo) earned accelerated approval from the US Food and Drug Administration (FDA) for the second-line treatment of primary biliary cholangitis (PBC) based on findings from the phase 3 ELATIVE trial evaluating the efficacy and safety of elafibranor 80 mg once daily versus placebo.¹

The decision made elafibranor the second FDA-approved second-line agent for PBC at the time, with obeticholic acid (Ocaliva) being the first. Just weeks after elafibranor was granted accelerated approval, seladelpar (Livdelzi) earned the same indication, marking the third second-line therapy for PBC in patients who have an inadequate response to or are unable to tolerate ursodeoxycholic acid.^1,2

While ELATIVE showed that treatment with elafibranor significantly improved prognostic biomarkers of cholestasis at 52 weeks, a poster presented at the American College of Gastroenterology (ACG) 2024 Scientific Sessions in Philadelphia, Pennsylvania, by Marcelo Kugelmas, MD, of South Denver Gastroenterology, provides an overview of how the peroxisome proliferator-activated receptors (PPAR) agonist is being explored in phase 3 and phase 4 trials in different patient populations with PBC.³

ELFIDENCE

A phase 3 randomized, long-term trial, ELFIDENCE will assess the use of elafibranor in patients with PBC and compensated cirrhosis, with a target enrollment of 276. In the trial, participants will be randomly assigned in a 1:1 ratio to receive elafibranor 80 mg or placebo and assessed over a maximum duration of 42 months.

The primary endpoint is event-free survival from randomization to the first occurrence of all-cause mortality, liver transplant or decompensation, change in model for end-stage liver disease 3.0 score, or the development of hepatocellular carcinoma. Safety endpoints include assessment of adverse events and clinically significant changes from baseline in laboratory tests and vital signs.

Initiated in August of 2023, the study is estimated to be completed in May of 2029.

ELSPIRE

A phase 3b randomized trial, ELSPIRE will evaluate the efficacy and safety of elafibranor in patients with PBC and an incomplete response to ursodeoxycholic acid, defined as alkaline phosphatase >1 × upper limit of normal (ULN) and < 1.67 × ULN, or intolerance to UDCA. The target enrollment is 72 participants who will be randomly assigned in a 2:1 ratio to elafibranor 80 mg or placebo and assessed over a 52-week treatment period.

The primary endpoint is the proportion of patients with alkaline phosphatase normalization at week 52. Safety endpoints include assessment of adverse events of varying severity and clinically significant changes from baseline in laboratory tests and vital signs.

Initiated in July of 2024, the estimated study completion is October of 2026.

ELFINITY

A prospective non-interventional, phase 4 multicenter study, ELFINITY will assess the effectiveness, safety, and tolerability of elafibranor in patients with PBC receiving treatment in real-world settings. Patients prescribed elafibranor as per the approved label and health professional decision are eligible for inclusion, with a target enrollment of 424 participants.

The primary endpoint is the proportion of patients with biochemical response to treatment at 6 months, defined as alkaline phosphatase < 1.67 × ULN with a reduction of ≥ 15% from baseline and total bilirubin ≤ ULN.

Initiated in July of 2024, the estimated study completion is July 2029.

References

1. ^{Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed November 5, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}
2. ^{Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 5, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}
3. ^{Kugelmas M, Kowdley KV, Hanson C, et al. P2877 - Elafibranor for the Treatment of Primary Biliary Cholangitis: Study Designs of the ELFIDENCE, ELSPIRE, and ELFINITY Phase III/IV Trials. Paper presented at: ACG 2024 Annual Scientific Meeting. Philadelphia, Pennsylvania. October 25-30, 2024.}