Efficacy and Safety of Fenebrutinib vs Teriflunomide in Relapsing Multiple Sclerosis: Results of the FENhance 1 and 2 Studies
Jiwon Oh1, Amit Bar-Or2, Gavin Giovannoni3, Maria Pia Sormani4, Martin S. Weber5, Sharon Stoll6, Jacqueline A. Nicholas7, H.-Christian von Büdingen8, Marquita Decker-Palmer9, Anastasia Loukitcheva9, Miriam Triyatni8, Nan Hu9, John N. Ratchford9, Julie Napieralski9, Alexandra Goodyear9, Ludwig Kappos10, Stephen Hauser11
1St. Michael's Hospital, University of Toronto, 2Perelman School of Medicine, University of Pennsylvania, 3Queen Mary University of London, 4University of Genoa, 5Institute of Neuropathology and Department of Neurology, University Medical Center and Fraunhofer Institute for Translational Medicine and Pharmacology, 6Advocare Stoll Medical Group, 7OhioHealth Multiple Sclerosis Centre, Riverside Methodist Hospital, 8F. Hoffmann-La Roche Ltd, 9Genentech, Inc., 10University Hospital and University Basel, Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), 11University of California San Francisco
Objective:
To evaluate the efficacy and safety of fenebrutinib vs teriflunomide in adults with relapsing multiple sclerosis (RMS).
Background:
With a dual mechanism of action, Bruton’s tyrosine kinase inhibitors (BTKis) may address both relapsing and progressive disease biologies in MS, which are major drivers of disability accumulation. To date, Phase III trials in patients with RMS have not met their primary endpoint in showing that covalent, irreversible BTKis reduce annualized relapse rate (ARR) vs teriflunomide. Fenebrutinib, a noncovalent, reversible, highly selective BTKi, has shown reductions in MRI disease activity in the Phase II FENopta study (NCT05119569) and its open-label extension, with an acceptable safety profile.
Design/Methods:
FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) are largely identical Phase III, multicenter, randomized, double-blind, double-dummy, parallel-group studies enrolling adults aged 18-55 years with RMS (2017 revised McDonald criteria; Expanded Disability Status Scale [EDSS] score 0-5.5). Patients were randomized 1:1 to oral fenebrutinib 200 mg twice daily or teriflunomide 14 mg once daily for a minimum of 96 weeks. The primary endpoint is ARR.
Results:
A total of 1497 patients were enrolled globally. The mean (SD) age at baseline was 35.8 (9.4) years, and the mean (SD) EDSS score was 2.5 (1.3). The mean (SD) duration since MS symptom onset was 5.5 (5.9), and the mean (SD) duration since diagnosis was 3.6 (5.1) years. Primary efficacy and safety data from both FENhance studies will be presented.
Conclusions:
The FENhance studies will provide evidence on the efficacy and safety of fenebrutinib vs teriflunomide in adult patients with RMS. While other BTKis have not shown superiority to teriflunomide in suppressing disease activity in RMS, the FENhance trials will determine whether fenebrutinib’s unique molecular design, optimized CNS exposure and promising Phase II results translate into significant benefits addressing both relapsing and progressive disease biologies in patients with RMS relative to teriflunomide.
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