Efficacy and Safety of Fenebrutinib vs Ocrelizumab in Primary Progressive Multiple Sclerosis: Primary Results of the Phase III FENtrepid Study
Amit Bar-Or1, Jiwon Oh2, Gavin Giovannoni3, Maria Pia Sormani4, Martin S. Weber5, Sharon Stoll6, Jacqueline A. Nicholas7, H.-Christian von Büdingen8, Jon Lopez9, Louise Roberts9, Miriam Triyatni8, Qi Qi9, John N. Ratchford9, Julie Napieralski9, Alexandra Goodyear9, Stephen L. Hauser10, Ludwig Kappos11
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 2St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada, 3Queen Mary University of London, London, UK, 4University of Genoa, Genoa, Italy, 5Institute of Neuropathology and Department of Neurology, University Medical Center and Fraunhofer Institute for Translational Medicine and Pharmacology, Göttingen, Germany, 6Advocare Stoll Medical Group, Philadelphia, PA, USA, 7OhioHealth Multiple Sclerosis Centre, Riverside Methodist Hospital, Columbus, OH, USA, 8F. Hoffmann-La Roche Ltd, Basel, Switzerland, 9Genentech, Inc., South San Francisco, CA, USA, 10University of California San Francisco, San Francisco, CA, USA, 11University Hospital and University Basel, Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Basel, Switzerland
Objective:
To evaluate the efficacy and safety of fenebrutinib compared with ocrelizumab in adult patients with primary progressive multiple sclerosis (pwPPMS).
Background:
Bruton's tyrosine kinase inhibitors (BTKi) have potential to impact both relapsing and progressive MS disease biologies. Fenbrutinib is an oral, highly selective, noncovalent, reversible BTKi that is CNS-penetrant, as shown in the Phase II FENopta study (NCT05119569) in relapsing MS in which fenebrutinib treatment rapidly reduced acute inflammatory disease activity. Currently the effect of fenebrutinib on progressive MS subtypes has not been demonstrated. Ocrelizumab remains the only approved treatment for PPMS, and an unmet need exists for treatments that can better control disability progression. FENtrepid (NCT04544449) is the first clinical trial of a new therapy in PPMS using ocrelizumab as an active comparator.
Design/Methods:
FENtrepid is a Phase III, multicenter, randomized, double-blind, double-dummy, parallel-group study evaluating the efficacy and safety of fenebrutinib compared with ocrelizumab in pwPPMS (18-65 years old; PPMS diagnosis [2017 revised McDonald criteria]; Expanded Disability Status Scale [EDSS] score 3.0-6.5). Patients were randomized 1:1 to either oral fenebrutinib 200 mg twice daily or intravenous ocrelizumab 600 mg every 24 weeks. The primary endpoint was time to onset of composite confirmed disability progression, defined as a 12-week confirmed increase in one or more of the EDSS, Timed 25-Foot Walk Test or 9-Hole Peg Test.
Results:
FENtrepid enrolled 985 patients with PPMS; 84% were not exposed to recent prior disease modifying therapies. Mean (SD) age at baseline was 48.9 (10.3) years. Median baseline EDSS score was 5.0; mean (SD) duration since MS symptom onset and diagnosis was 9.0 (6.7) and 4.7 (5.4) years, respectively. Primary efficacy and safety results will be presented.
Conclusions:
FENtrepid will provide the first evidence on the effect of fenebrutinib treatment on disability progression in PPMS, relative to an active comparator of ocrelizumab.
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