Elafibranor (Iqirvo®): A Comprehensive Monograph on a First-in-Class PPAR Agonist for the Treatment of Primary Biliary Cholangitis

I. Executive Summary and Drug Profile

Introduction

Elafibranor, marketed under the proprietary name Iqirvo®, is a first-in-class, orally administered, once-daily dual peroxisome proliferator-activated receptor (PPAR) alpha (PPARα) and delta (PPARδ) agonist.[1] It has received accelerated or conditional approval in major global jurisdictions, including the United States and the European Union, for the treatment of Primary Biliary Cholangitis (PBC).[2] The approved indication is for adult patients who have demonstrated an inadequate response to, or who are intolerant of, the established first-line therapy, ursodeoxycholic acid (UDCA).[5] This monograph provides an exhaustive analysis of Elafibranor's pharmacology, the pivotal clinical evidence supporting its approval, its comprehensive safety profile, and its therapeutic position within the evolving landscape of PBC management.

Key Attributes

Elafibranor's novel mechanism of action, targeting the fundamental metabolic and inflammatory pathways of PBC, represents a significant departure from existing therapeutic modalities.[7] Its regulatory approvals are primarily based on the robust results of the pivotal Phase 3 ELATIVE trial, which demonstrated a statistically and clinically significant improvement in the primary biochemical endpoint—a composite of alkaline phosphatase (ALP) and total bilirubin levels—compared to placebo.[9] A defining characteristic that distinguishes Elafibranor from the alternative second-line therapy, obeticholic acid (OCA), is its favorable profile concerning pruritus. Pruritus is a common and often debilitating symptom of PBC that can be exacerbated by OCA, whereas Elafibranor has been shown to not worsen this symptom, thereby addressing a critical unmet need in patient management.[7]