ACTRIMS 2026: Roche’s investigational therapy fenebrutinib shows breakthrough results in primary progressive multiple sclerosis (PPMS)
- ipharmaservices
- 6 hours ago
- 2 min read
Roche has released new late-breaking Phase III data demonstrating that its experimental Bruton’s tyrosine kinase (BTK) inhibitor, fenebrutinib showing potential in patients with primary progressive multiple sclerosis (PPMS).
Findings from the pivotal FENtrepid trial, presented at the ACTRIMS forum, indicate that fenebrutinib met its primary endpoint of non-inferiority to the current standard therapy, OCREVUS (ocrelizumab), in delaying disability progression among people with PPMS.
In the study, fenebrutinib reduced the risk of confirmed disability progression by 12% compared with Ocrevus, with treatment separation observed as early as 24 weeks. The benefit was consistent across different patient subgroups and sustained throughout the trial period. Notably, fenebrutinib also showed potential improvement in upper limb function, a key measure of disease impact in PPMS.
Key results from FENtrepid
The primary assessment, 12-week composite confirmed disability progression (cCDP12), integrated three clinical measures:
Expanded Disability Status Scale (EDSS): to evaluate overall functional disability
Timed 25-Foot Walk (T25FW): to measure ambulatory speed
Nine-Hole Peg Test (9HPT): to assess hand and arm coordination
The largest benefit was seen in upper limb function, where fenebrutinib reduced the risk of worsening on the 9HPT by 26%. A post-hoc analysis further highlighted a 22% lower risk of progression on a composite endpoint combining the EDSS and 9HPT compared with OCREVUS.
About the FENtrepid trial of fenebrutinib
FENtrepid is a Phase III, randomized, double-blind, double-dummy, parallel-group study involving 985 adults diagnosed with PPMS. Participants were randomly assigned (1:1) to receive either daily oral fenebrutinib (plus an intravenous placebo mimicking OCREVUS) or intravenous OCREVUS (plus an oral placebo) for a minimum duration of 120 weeks.
The study’s primary endpoint was the time to onset of 12-week composite confirmed disability progression (cCDP12). This measure is more comprehensive than the EDSS alone, capturing multiple dimensions of physical disability, ambulation, dexterity, and overall function, and allowing earlier detection of disease progression. Key secondary outcomes included 24-week composite confirmed disability progression (cCDP24) and confirmed EDSS progression at 12 and 24 weeks. After the blinded phase, participants could transition into an open-label extension, continuing treatment with fenebrutinib to assess long-term efficacy and safety.
About fenebrutinib and Mechanism of action
Fenebrutinib is a novel, reversible, non-covalent, oral BTK inhibitor specifically designed to penetrate the central nervous system (CNS). Unlike many existing BTK inhibitors that bind to the BTK enzyme irreversibly, fenebrutinib’s reversible mechanism allows it to disengage from the enzyme, potentially reducing off-target interactions and improving safety. Its optimized pharmacokinetic properties and high potency make it a promising candidate not only for PPMS but also for relapsing forms of multiple sclerosis (RMS).
If approved, fenebrutinib could become the first oral BTK inhibitor with demonstrated effectiveness in slowing disability progression in PPMS, marking a major advance for people living with this challenging neurological condition.