Roche’s fenebrutinib met primary endpoint in Phase III FENhance 1 (NCT04586010), reducing ARR by 51% vs. teriflunomide in RMS consistent with FENhance 2’s 59% reduction. Full data at AAN 2026; potential first high-efficacy oral MS therapy.
Written By: Pharmacally Medical News Desk
Roche today announced positive topline results from its pivotal Phase III FENhance 1 (NCT04586010) study of fenebrutinib, an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor, in relapsing multiple sclerosis (RMS).
The trial met its primary endpoint, demonstrating a statistically significant 51% reduction in annualized relapse rate (ARR) compared to teriflunomide over at least 96 weeks results consistent with the companion FENhance 2 study, which showed a 59% ARR reduction. Combined, these data translate to roughly one relapse every 17 years.
Secondary endpoints in both RMS studies also favored fenebrutinib, with significant reductions in brain lesions, including T1-gadolinium-enhancing and new/enlarging T2-weighted lesions on MRI.
All disability progression measures, such as 12- and 24-week confirmed composite disability progression (cCDP12 and cCDP24) incorporating EDSS, timed 25-foot walk, and nine-hole peg test, showed favorable trends.
- These findings build on November’s positive results from FENhance 2 (NCT04586023) in RMS and FENtrepid (NCT04544449) in primary progressive MS (PPMS), positioning fenebrutinib as a potential first high-efficacy oral therapy for both relapsing and progressive forms. Full data from FENhance 1 and 2 will be presented at the American Academy of Neurology (AAN) Annual Meeting 2026 and submitted to regulators alongside FENtrepid results.
“Fenebrutinib provides convincing evidence as the first high-efficacy oral treatment for RMS and PPMS,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We’re advancing innovation to help people with MS live without disability.”
Fenebrutinib’s non-covalent, reversible design offers high potency, selectivity (130-fold over other kinases), and blood-brain barrier penetration. It targets B cells to curb relapsing inflammation and microglia to address chronic CNS damage driving progression addressing an unmet need where 30% of patients remain on low-efficacy orals despite CD20 therapies.
Safety Profile
FENhance 1 and 2 enrolled 1,497 RMS patients in double-blind, teriflunomide-controlled trials (1:1 randomization, oral fenebrutinib BID vs. teriflunomide QD). Liver transaminase elevations matched teriflunomide; one asymptomatic Hy’s Law case occurred per arm in FENhance 1, resolving post-discontinuation, with none elsewhere in the MS or autoimmune programs.
One fatal case occurred in the teriflunomide arm across RMS studies; eight varied fatalities arose in fenebrutinib arms, under further analysis. Patients may enter open-label extension with fenebrutinib.
Over 2,700 participants have received fenebrutinib across Phase I-III trials in MS and autoimmune diseases. MS affects 2.9 million worldwide, with RMS in approx. 85% and PPMS in approx.15%; OCREVUS remains the sole PPMS-approved therapy.
Fenebrutinib could transform MS management by combining relapse prevention with progression slowing in an oral format.
References
[Ad hoc announcement pursuant to Art. 53 LR] 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), 02 March 2026, [Ad hoc announcement pursuant to Art. 53 LR] Roche’s fenebrutinib confirms its potential as first and only BTK inhibitor for relapsing and primary progressive MS in third positive Phase III study (…
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance), ClinicalTrials.gov ID NCT04586010, https://clinicaltrials.gov/study/NCT04586010
Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance 2), ClinicalTrials.gov ID NCT04586023, https://clinicaltrials.gov/study/NCT04586023
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Ocrelizumab in Adult Participants with Primary Progressive Multiple Sclerosis (FENtrepid), ClinicalTrials.gov ID NCT04544449, https://clinicaltrials.gov/study/NCT04544449