BTK Inhibitor Compared With Ocrelizumab for Primary Progressive MS

Study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026 demonstrated that fenebrutinib (Roche, Basel, Switzerland), an investigational oral Bruton tyrosine kinase (BTK) inhibitor, achieved noninferior efficacy compared with Ocrevus (ocrelizumab; Genentech, South San Francisco, CA) in people with primary progressive multiple sclerosis (PPMS).

The multicenter, randomized, double-blind, double-dummy phase 3 FENtrepid study (NCT04544449) included 985 adults with PPMS. Participants were randomized 1:1 to receive either daily oral fenebrutinib plus placebo infusions or intravenous ocrelizumab plus oral placebo for at least 120 weeks. The primary end point was time to onset of 12-week composite confirmed disability progression (cCDP12), a measure incorporating Expanded Disability Status Scale (EDSS) progression, timed 25-foot walk (T25FW), and nine-hole peg test (9HPT) performance.

Key findings from the study include the following:

• Fenebrutinib treatment reduced the risk of 12-week composite confirmed disability progression (cCDP12) by 12% compared with ocrelizumab in patients with PPMS (hazard ratio [HR], 0.88; 95% CI, 0.75 to 1.03).
• Fenebrutinib treatment reduced the risk of worsening on the 9HPT by 26% compared with Ocrevus (HR, 0.74; 95% CI, 0.56 to 0.98).
• Common adverse event rates (≥10%) were comparable between patients treated with fenebrutinib vs Ocrevus, including infections (67.0% vs 70.9%), nausea (12.0% vs 7.1%), and hemorrhage (10.2% vs 8.1%), with comparable rates of serious adverse events (19.1% vs 18.9%) and treatment discontinuation due to AEs (4.3% vs 3.0%).
• Transient, reversible elevations in liver enzymes occurred more often in people treated with fenebrutinib (13.3% vs 2.9%).

Source: Roche. Roche’s fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS). Published February 6, 2026. Accessed February 9, 2026. https://www.roche.com/media/releases/med-cor-2026-02-07