In Relapsing MS, BTK Inhibitor Fenebrutinib Showed Reduced Relapse Rate vs Aubagio

Key Takeaways

• Results from the phase 3 FENhance 1 trial showed fenebrutinib reduced annualized relapse rate compared with Aubagio in people with relapsing multiple sclerosis.
• Combined results from FENhance 1 and FENhance 2 equate to 1 relapse every 17 years, according to a statement from Roche.
• If approved, fenebrutinib could be the first oral BTK inhibitor with high efficacy for treatment of relapsing and primary progressive multiple sclerosis.

Fenebrutinib (Roche, Basel, Switzerland), an investigational oral Bruton tyrosine kinase (BTK) inhibitor, reduced relapse activity compared with Aubagio (teriflunomide; Sanofi, Paris, France) in people with relapsing multiple sclerosis (RMS) according to results of the phase 3 FENhance 1 trial (NCT04586010). The findings add to Roche’s broader phase 3 program evaluating fenebrutinib in relapsing and progressive forms of MS. Fenebrutinib is a noncovalent, reversible BTK inhibitor designed to target B-cell–mediated inflammation and microglial activity within the central nervous system.

FENhance 1 and FENhance 2 (NCT04586023) are multicenter, randomized, double-blind, double-dummy, parallel-group phase 3 studies comparing oral fenebrutinib with Aubagio in a combined total of 1497 adults with RMS. Participants were randomized 1:1 to receive fenebrutinib twice daily (with Aubagio-matched placebo) or Aubagio once daily (with fenebrutinib-matched placebo) for at least 96 weeks. The primary end point was annualized relapse rate (ARR), and MRI lesion activity and disability-progression composites (12- and 24-week composite confirmed disability progression [cCDP12/cCDP24] incorporating Expanded Disability Status Scale [EDSS] progression, timed 25-foot walk [T25FW], and nine-hole peg test [9HPT] performance) were key secondary measures.

The results showed:

• Fenebrutinib reduced ARR by 51% versus Aubagio in FENhance 1, consistent with a 59% ARR reduction reported in FENhance 2.
• Secondary end points showed statistically significant, clinically meaningful reductions in brain lesions, while disability progression end points showed favorable trends for fenebrutinib.
• Liver transaminase elevations were comparable to Aubagio; FENhance 1 reported 1 asymptomatic Hy’s Law case in each arm that resolved after treatment discontinuation.
• Fatal events included 1 case in the Aubagio arm and 8 cases (varied causes and different treatment time points) in the fenebrutinib arms, with additional analyses ongoing.

Source: Roche. Roche's fenebrutinib confirms its potential as first and only BTK inhibitor for relapsing and primary progressive MS in third positive phase III study (FENhance 1). Published March 1, 2026. Accessed March 4, 2026 https://www.roche.com/media/releases/med-cor-2026-03-02