P2877 - Elafibranor for the Treatment of Primary Biliary Cholangitis: Study Designs of the ELFIDENCE, ELSPIRE, and ELFINITY Phase III/IV Trials

Marcelo Kugelmas, MD¹, Kris V.. Kowdley, MD, FACG², Christina Hanson, FNP, MSN¹, Mordechai Rabinovitz, MD³, Marwan Sleiman, PhD⁴, Richard Allan, PhD⁵, Katerine Boutros, PharmD⁶, Ana Bozas, PhD⁶, Christelle Pommie, M2⁴, Jianfen Shu, PhD⁶, Nuno Antunes, PhD⁶, Jörn M. Schattenberg, MD^7
1South Denver Gastroenterology, Englewood, CO; ²Liver Institute Northwest, Seattle, WA; ³University of Pittsburgh, Pittsburgh, PA; ⁴Ipsen, Boulogne-Billancourt, Ile-de-France, France; ⁵Ipsen, London, England, United Kingdom; ⁶Ipsen, Cambridge, MA; ⁷Saarland University Medical Center, Homburg, Saarland, Germany

Introduction: Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Elafibranor, a peroxisome proliferator-activated receptor (PPAR)-α/δ agonist, significantly improved prognostic biomarkers of cholestasis at Week (Wk) 52 in participants (pts) with PBC in the phase III ELATIVE® trial (NCT04526665).¹ Here, we describe methodologies of the ELFIDENCE (NCT06016842), ELSPIRE (NCT06383403), and ELFINITY (NCT06447168) trials designed to further evaluate the safety and efficacy of elafibranor in the treatment of PBC, including assessing complementary populations not yet analyzed, and providing data on long-term clinical outcomes and/or in real-world settings.

Methods: Primary and secondary efficacy endpoints for each trial are presented in the Table.
ELFIDENCE: A phase III randomized, long-term trial of elafibranor in pts with PBC and compensated cirrhosis. Pts will be randomized to elafibranor (80mg) or placebo and assessed over a maximum duration of 42 months (target enrollment=276). Safety endpoints include assessment of adverse events (AEs) and clinically significant changes from baseline in laboratory tests and vital signs.
ELSPIRE: A phase IIIb randomized trial to evaluate the efficacy and safety of elafibranor in pts with PBC and an incomplete response (defined as alkaline phosphatase [ALP] >1 × upper limit of normal [ULN] and < 1.67 × ULN) on (ursodeoxycholic acid) UDCA or intolerance to UDCA. Pts will be assessed over a 52-wk treatment period (target enrollment=72). Safety endpoints include assessment of AEs of varying severity and clinically significant changes from baseline in laboratory tests and vital signs.
ELFINITY: A prospective non-interventional, phase IV multicenter study to assess the effectiveness, safety, and tolerability of elafibranor in pts with PBC receiving treatment in real-world settings. Pts prescribed elafibranor as per approved label and health professional decision are eligible for inclusion (target enrollment=424).

Results: -

Discussion: Results of the ELFIDENCE, ELSPIRE, and ELFINITY trials will facilitate further evaluation of the efficacy and safety of elafibranor in the treatment of pts with PBC, provide data for additional patient populations, and evaluate elafibranor in real-world settings and long-term.

1. Kowdley KV et al. N Engl J Med. 2024;390(9):795–805.


Disclosures:


Marcelo Kugelmas, MD¹, Kris V.. Kowdley, MD, FACG², Christina Hanson, FNP, MSN¹, Mordechai Rabinovitz, MD³, Marwan Sleiman, PhD⁴, Richard Allan, PhD⁵, Katerine Boutros, PharmD⁶, Ana Bozas, PhD⁶, Christelle Pommie, M2⁴, Jianfen Shu, PhD⁶, Nuno Antunes, PhD⁶, Jörn M. Schattenberg, MD⁷. P2877 - Elafibranor for the Treatment of Primary Biliary Cholangitis: Study Designs of the ELFIDENCE, ELSPIRE, and ELFINITY Phase III/IV Trials, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.