http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Safety and efficacy of elafibranor in primary sclerosing cholangitis
the ELMWOOD phase II randomized-controlled trial
Background & Aims - Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease. Elafibranor, a dual peroxisome proliferator-activated receptor-α/δ agonist, was investigated in the phase II ELMWOOD trial (NCT05627362). - Methods - This 12-week, double-blind trial enrolled adults with PSC and alkaline phosphatase (ALP) ≥1.5× the upper limit of normal. The primary endpoint was elafibranor safety vs. placebo. Additional endpoints included relative mean change from baseline in ALP and enhanced liver fibrosis (ELF) score. - Results - A total of 68 participants (male: 54.4%; mean age: 46.3 years; inflammatory bowel disease: 55.9%) were randomized to elafibranor 80 mg (n = 22), elafibranor 120 mg (n = 23), or placebo (n = 23). At baseline, 70.6% were on ursodeoxycholic acid, 48.5% had ELF scores >9.8, and the mean ALP level was 369.5 U/L. At Week 12, rates of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation in participants on elafibranor 80 mg, 120 mg, and placebo were 68.2%, 78.3%, and 69.6%, and 4.5%, 4.3%, and 8.7%, respectively. Serious TEAEs occurred only in participants on placebo (4.3%). Participants on elafibranor 80 mg and 120 mg had reductions in ALP vs. placebo (least squares mean treatment difference [95% CI]: −35.3% [−49.2, −21.4] and −54.7% [−68.3, −41.0], respectively). ALP normalization occurred only in participants on elafibranor 80 mg (9.1%) and 120 mg (17.4%). The LS mean treatment differences (95% CI) in change from baseline in ELF scores in participants on elafibranor 80 mg and 120 mg vs. placebo were -0.19 (−0.52, +0.15) and -0.28 (−0.62, +0.06), respectively. - Conclusions - Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo. A greater magnitude of response was observed with elafibranor 120 mg compared with 80 mg. - Impact and implications - For people with primary sclerosing cholangitis (PSC), there is a need for a well-tolerated and effective treatment that will enhance quality of life, prevent disease progression, and improve long-term outcomes. Here, we present results from the double-blind period of the phase II ELMWOOD trial in PSC, wherein elafibranor, a peroxisome proliferator-activated receptor-α/δ agonist, demonstrated a favorable safety profile, provided greater biochemical improvements over 12 weeks compared with placebo, and appeared to stabilize markers of fibrosis and improve pruritus. These findings support larger and longer term investigations of elafibranor to explore its therapeutic potential as a treatment for people with PSC.
Cynthia Levy, George F. Abouda, Bahri M. Bilir, Alan Bonder, Christopher L. Bowlus, Isabel Campos-Varela, Nora Cazzagon, Natasha Chandok, Kuldeep Cheent, Helena Cortez-Pinto, Münevver Demir, Michael T. Dill, Bertus Eksteen, Jonathan M. Fenkel, Richard Gilroy, Hin Hin Ko, Ira M. Jacobson, Yiannis Kallis, Marcelo Kugelmas, Velimir Luketic, Alessandra Mangia, Aldo J. Montano-Loza, Ashis Mukhopadhya, Antonio Olveira, Bhaktasharan C. Patel, Antonello Pietrangelo, Faruq Pradhan, Magdalena Salcedo, Mitchell L. Shiffman, Kathrin Sprinzl, Rachael Swann, Douglas Thorburn, Paul J. Thuluvath, Palak J. Trivedi, Juan Turnes, Claudia O. Zein, Hugo Gomes da Silva, Seema Jaitly, Benjamin Miller, Claire Milligan, Aude Tavenard, Kris V. Kowdley
Safety and efficacy of elafibranor in primary sclerosing cholangitis the ELMWOOD phase II randomized-controlled trial
Amsterdam [u.a.] : Elsevier Science, 1985