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Elafibranor in primary biliary cholangitis: Two-year placebo-controlled outcomes and long-term open-label data from
Kris V Kowdley1, Christopher L Bowlus2, Cynthia Levy3
1Liver Institute Northwest and Velocity Clinical Research, Seattle, Washington, USA; Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USA.
Background & Aims:
We report 104-week placebo-controlled data and long-term open-label extension (OLE) data from the ongoing ELATIVE® phase III trial (NCT04526665) of elafibranor in primary biliary cholangitis (PBC).
Methods:
A total of 161 patients were randomized 2:1 to elafibranor 80 mg or placebo. The double-blind period (DBP) consisted of 52-week common (Part 1) and variable (Part 2) periods. Patients completing Part 1 continued into Part 2 until all patients completed Part 1, or for a maximum of 104 weeks. All patients completing Part 1 could enter the OLE and receive elafibranor.
Results:
At Week 104 in DBP Part 2, 64.3% (18/28) and 10.7% (3/28) of elafibranor-treated patients achieved biochemical response and alkaline phosphatase (ALP) normalization, respectively, vs. no placebo-treated patients. In patients with moderate-to-severe fatigue or pruritus at baseline, mean (SE) changes to Week 104 in PROMIS Fatigue Short Form 7a (PFSF 7a) and PBC Worst-Itch Numeric Rating Scale (PBC WI NRS) were -6.3 (2.2) vs. -0.4 (1.2) and -4.1 (1.0) vs. 0.3 (1.2), respectively, with elafibranor vs. placebo. A total of 138 patients entered the OLE (continuous elafibranor: n = 93; crossover elafibranor: n = 45). Among patients continuing elafibranor, 58.8% (47/80) and 65.0% (13/20) achieved biochemical response, and 15.0% (12/80) and 25.0% (5/20) achieved ALP normalization at Weeks 104 and 156, respectively. In crossover patients, 51.2% (21/41) and 22.0% (9/41) achieved biochemical response and ALP normalization after 52 weeks, respectively. In patients continuing elafibranor with moderate-to-severe symptoms at baseline, mean (SE) changes to Week 130 in PFSF 7a and PBC WI NRS were -4.8 (1.5) and -4.0 (0.7), respectively. There were no unexpected safety findings.
Conclusions:
Through 3 years of treatment, elafibranor led to sustained biochemical improvements and was generally well tolerated, with numerical improvements in fatigue and pruritus.
Impact And Implications:
Given the chronic, progressive nature of primary biliary cholangitis (PBC), the long-term efficacy and tolerability of treatments is important. Here, we present 2-year results from the double-blind period, and long-term data from the ongoing open-label extension of the phase III ELATIVE® trial, wherein elafibranor (a peroxisome proliferator-activated receptor-α/δ agonist) treatment led to sustained biochemical improvements, stable non-invasive tests of fibrosis, and numerical improvements in fatigue and pruritus, through 3 years. Elafibranor demonstrated a favorable safety profile up to a maximum treatment exposure of 3.5 years, including in patients crossing over from placebo. These findings support elafibranor as a durable long-term treatment for patients with PBC, and are particularly relevant for clinicians managing patients with inadequate response or intolerance to first-line treatments.
Trial Registration:
NCT04526665 (https://clinicaltrials.gov/study/NCT04526665); first registered 08/26/2020.
