The Safety Profile of Fenebrutinib in Patients with Multiple Sclerosis Is Consistent with Those in Previously Studied Autoimmune Indications
Jiwon Oh1, Anastasiia Raievska2, Malgorzata Sierzega2, João Cerqueira3, Claire S. Riley4, Maresa Caunt5, John N. Ratchford5, Alexandra Goodyear5, Konstantina Vanevski2, Maria Pia Sormani6, Gavin Giovannoni7
1St. Michael's Hospital, University of Toronto, 2F. Hoffmann-La Roche Ltd, 3University of Minho, 4Columbia University Medical Center, 5Genentech Inc., 6University of Genoa, 7Blizard University, Queen Mary University of London
Objective:
To compare the safety and tolerability of fenebrutinib in people with multiple sclerosis (MS) and those with autoimmune indications (AIs).
Background:
Fenebrutinib is a potent, highly selective, reversible oral Bruton’s tyrosine kinase inhibitor being evaluated in a Phase 3 clinical program for MS. Fenebrutinib has been studied in relapsing MS (RMS) and three AIs (rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], chronic spontaneous urticaria [CSU]).
Design/Methods:
Adverse events (AEs) and safety laboratory tests were analyzed for patients who received fenebrutinib at the highest dose (200 mg twice daily [BID]) or placebo in Phase 2 studies of MS and AIs.
Results:
Across Phase 2 studies, 73 patients with RMS and 577 patients with AIs received fenebrutinib 200 mg BID, and 36 with RMS and 278 with AIs received placebo/standard of care. AEs reported in >5% of fenebrutinib-treated patients with RMS were abnormal hepatic transaminase elevation and urinary tract infection (5.5% each). There was no imbalance in rate of infections between treatment arms, and no serious or fatal AEs were reported across all indications. Grade ≥2 hepatic transaminase elevations were observed more frequently in the fenebrutinib vs placebo arms: RMS, 8.2% vs 2.8%; across AIs, 4% vs 1.4% (RA, 1.9% vs 1.3%; SLE, 4.5% vs 2.4%; CSU, 9.6% vs 0%). Nonserious Grade 1 bleeding/bruising AEs were reported in 1.4% of RMS-fenebrutinib (n=1) and 7.7% AI-fenebrutinib (n=23) patients vs 0% RMS-placebo (n=36) and 3.2% AI-placebo (n=9) patients. Irrespective of the indication, there were no cases of major hemorrhage (Grade ≥3, serious) or cardiovascular events reported in patients receiving fenebrutinib.
Conclusions:
The safety and tolerability profile of fenebrutinib in MS remains consistent with that in previously studied AIs (RA, SLE and CSU). These data further support fenebrutinib’s favorable safety profile as well as its clinical development across the Phase 3 MS clinical program.