South San Francisco, California, U.S., September 29, 2026
Genentech, a member of the Roche Group, announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for fenebrutinib under priority review for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). Fenebrutinib is an investigational oral, non-covalent and reversible Bruton’s tyrosine kinase (BTK) inhibitor designed to target biological mechanisms associated with both relapses and disability progression in multiple sclerosis. The regulatory filing is supported by results from three Phase III studies, including FENhance 1 and FENhance 2 in relapsing multiple sclerosis and FENtrepid in primary progressive multiple sclerosis. Genentech reported that the comprehensive clinical program demonstrated reductions in relapses and brain lesions in RMS, while the PPMS study showed a numerical reduction in the risk of disability progression compared with Ocrevus.
Fenebrutinib Demonstrates Relapse Reduction in RMS
The FENhance 1 and FENhance 2 Phase III studies evaluated fenebrutinib in patients with relapsing multiple sclerosis and compared the investigational treatment with teriflunomide, an established standard-of-care therapy. Over 96 weeks, fenebrutinib reduced the annualized relapse rate by 51.1% in FENhance 1 and 58.5% in FENhance 2 compared with teriflunomide, with both results reaching statistical significance. Genentech also reported reductions in active and chronic brain lesions, providing evidence of effects on measures of disease activity beyond clinical relapses. Measures of disability progression, including 12-week composite confirmed disability progression (cCDP12), showed consistent positive trends favoring fenebrutinib over teriflunomide. According to Genentech, the relapse-rate findings corresponded to an estimated frequency of approximately one relapse every 17 years in the Phase III studies, although such estimates are derived from trial-level relapse rates and should not be interpreted as an individual patient’s expected disease course.
Phase III PPMS Study Shows Disability Progression Data
The FENtrepid Phase III study evaluated fenebrutinib in people with primary progressive multiple sclerosis, a form of MS characterized by steadily worsening disability rather than distinct relapses. The study met its primary endpoint of non-inferiority compared with Ocrevus (ocrelizumab) in reducing disability progression. Genentech reported that fenebrutinib numerically reduced the risk of disability progression by 12% compared with Ocrevus, based on time to onset of cCDP12, with a hazard ratio of 0.88 and a 95% confidence interval of 0.75 to 1.03. The company also reported that treatment effects were observed across patient subgroups, including participants without active inflammation, and continued throughout the treatment period after Week 24. Fenebrutinib is designed to cross the blood-brain barrier and inhibit both B cells and microglia, potentially addressing acute inflammatory activity associated with relapses and chronic inflammation within the central nervous system.
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Genentech Advances BTK Inhibitor Toward FDA Review
Fenebrutinib is an investigational CNS-penetrant BTK inhibitor that differs from many other BTK inhibitors because it binds reversibly and non-covalently to the BTK enzyme. Its development program is intended to address both relapsing and progressive aspects of multiple sclerosis. The safety database includes more than 2,700 study participants across Phase III and earlier clinical studies. Genentech reported that serious adverse-event rates were 9% for both fenebrutinib and teriflunomide in FENhance 1, 11% versus 6% in FENhance 2, and 19% for both fenebrutinib and Ocrevus in FENtrepid. Liver enzyme elevations were comparable between fenebrutinib and teriflunomide in the RMS studies but occurred more frequently with fenebrutinib than Ocrevus in FENtrepid. The company also noted an imbalance in reported fatalities across the three pivotal studies, with deaths occurring at different times and from various causes. Genentech described the overall safety profile as manageable while acknowledging these safety findings.
The FDA’s acceptance of the NDA under priority review marks a significant regulatory milestone for Genentech’s multiple sclerosis program. If approved, fenebrutinib would represent a new oral treatment option being evaluated for both relapsing and primary progressive multiple sclerosis. The FDA review will determine whether the clinical evidence supports approval and the appropriate labeling for the investigational medicine.
Source: Genentech press release
