Roche reports Phase III fenebrutinib data showing up to 30% lower slowly expanding lesion volume and 62% lower paramagnetic rim lesion accumulation in multiple sclerosis.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Roche reported new Phase III findings for fenebrutinib, an investigational oral, reversible, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor being evaluated in relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). Presented at MSToronto2026, the results showed reductions in slowly expanding lesion (SEL) volume in both forms of MS and reduced accumulation of paramagnetic rim lesions (PRLs) in RMS.
The findings address an important limitation of current MS treatment assessment. Relapse control and prevention of new MRI lesions measure inflammatory disease activity, but chronic inflammation within existing lesions may also contribute to progressive tissue damage and long-term disability.
Fenebrutinib Reduced Slowly Expanding Lesion Volume
Across the Phase III FENhance 1 and FENhance 2 studies in RMS and the FENtrepid study in PPMS, fenebrutinib reduced SEL volume by up to 30% compared with active comparators. The reductions were reported over 96 weeks in RMS and 120 weeks in PPMS, with statistical significance at p<0.001.
SELs are existing MS lesions that gradually expand over time and are associated with chronic tissue injury. Their assessment may provide additional information about disease processes that conventional relapse and MRI activity measures do not fully capture.
The results extend the evidence supporting fenebrutinib beyond acute inflammatory disease activity. However, a reduction in lesion volume is an imaging outcome and does not independently establish that treatment will prevent long-term disability.
Reduced Accumulation of Paramagnetic Rim Lesions
In RMS, fenebrutinib reduced PRL accumulation by 62% compared with an active comparator (p=0.001).
PRLs are MRI-visible lesions associated with iron-containing immune cells at lesion edges. They are of particular interest in MS research because they can indicate persistent inflammatory activity within the central nervous system.
The combination of reduced SEL volume and PRL accumulation provides evidence across two imaging measures associated with chronic lesion activity. Although these findings support further investigation of BTK inhibition in MS, the reported 62% reduction should not be interpreted as an equivalent reduction in disability or overall disease progression.
Pooled FENhance Results Show Broader Disease Activity Benefits
Roche also reported pooled results from the Phase III FENhance 1 and FENhance 2 studies, which compared fenebrutinib with teriflunomide in RMS. Over 96 weeks, the analysis showed:
- 55% lower annualised relapse rate (ARR) with fenebrutinib (p<0.001).
- 75% of patients achieved no evidence of disease activity (NEDA-3), representing a reported 70% reduction in the risk of not achieving NEDA-3 (p<0.001).
- 23% less annual total brain volume loss (p<0.001).
- 16% lower risk of 12-week composite confirmed disability progression (p=0.04).
NEDA-3 generally denotes the absence of relapses, confirmed disability worsening and new or enlarging MRI lesions over a defined period. The reported result suggests more comprehensive disease activity control, although the composite measure should be interpreted alongside its individual components and prespecified statistical analysis.
The disability-progression finding is also relevant, but its clinical significance requires consideration of the endpoint definition, confidence intervals, follow-up duration and multiplicity-adjustment plan. The reported 16% reduction, with p=0.04, warrants careful interpretation rather than being treated as definitive evidence of durable disability prevention.
How BTK Inhibition May Affect MS Pathology
Fenebrutinib inhibits BTK, an enzyme involved in signalling within B cells and myeloid-lineage immune cells, including microglia in the central nervous system. These cells participate in immune processes implicated in MS.
Fenebrutinib is designed to cross the blood-brain barrier, potentially enabling activity both in the periphery and within the brain. This provides a biological rationale for evaluating its effects on relapses alongside chronic lesion activity and brain volume loss.
However, the mechanism alone does not establish clinical efficacy, and the reported imaging findings do not independently prove the extent to which central nervous system activity accounts for the observed treatment effects.
Additional Findings Across Roche’s Neurology Programme
Roche also reported results from two other studies at MSToronto2026.
In the Phase III OPERETTA 2 study, 90% of children aged 10–17 years with relapsing-remitting MS remained relapse-free over two years while receiving ocrelizumab (Ocrevus). Pre-existing vaccine immunity was preserved in 81–100% of participants across the reported assessments. The European Commission approved Ocrevus for paediatric MS on October 15, 2026.
In the Phase III METEOROID study in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), exploratory analyses of relapse recovery showed a median Expanded Disability Status Scale (EDSS) change 12 weeks after relapse of −2 with satralizumab (Enspryng), compared with −0.5 with placebo. Overall function remained stable with satralizumab and worsened with placebo, according to Roche.
These findings concern different treatments, patient populations and clinical questions. They should be evaluated independently and do not provide evidence of fenebrutinib’s efficacy.
Clinical Interpretation and Next Steps
The distinguishing feature of Roche’s fenebrutinib findings is the combination of reduced chronic lesion activity with improvements across several conventional disease activity measures in RMS. The SEL and PRL results broaden the assessment of treatment effects beyond relapses and new MRI lesions, while the pooled FENhance findings provide additional evidence across relapse, brain volume and disability-related outcomes.
Nevertheless, the magnitude and durability of clinical benefit require assessment against the complete trial datasets, including safety outcomes, discontinuations, confidence intervals and prespecified statistical analyses.
Roche announced on September 30, 2026, that the US Food and Drug Administration had accepted its New Drug Application for fenebrutinib under priority review for RMS and PPMS. The medicine remains investigational and has not yet received FDA approval.
For clinicians, the key question is whether the observed imaging changes translate into sustained, meaningful benefits for patients, particularly in preserving neurological function and limiting disability over time. Full study results and regulatory review will help clarify fenebrutinib’s benefit-risk profile relative to available treatments.
References
Roche presents new pivotal trial data across broad neuroimmunology portfolio at MSToronto2026, Roche, 21 October 2026
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance), ClinicalTrials.gov ID NCT04586010
Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance 2), ClinicalTrials.gov ID NCT04586023
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.