Roche/Genentech frame fenebrutinib as a potentially transformative single oral therapy for MS, pending regulatory review, that could cover both RMS and PPMS.

Genentech is emphasizing a broader neuroscience focus, with fenebrutinib being explored across autoimmune diseases beyond MS.

Fenebrutinib inhibits BTK via a non-covalent, CNS-penetrant mechanism aimed at addressing both B cell/microglia biology and progressive disease, with a design to minimize off-target effects.

Roche plans to present the full three-study dataset at the American Academy of Neurology 2026 meeting and submit the combined data to regulators, underscoring the intent to seek broad approval.

Genentech's Phase III program—FENhance 1 and 2 for relapsing MS and FENtrepid for primary progressive MS—positions fenebrutinib as a potential first high-efficacy oral BTK inhibitor capable of addressing both RMS and PPMS.

In FENhance 1, fenebrutinib reduced the annualized relapse rate by about half versus teriflunomide over roughly three years of follow-up, with FENhance 2 showing an even larger 59% reduction, supporting a consistent relapsing MS signal.

In the PPMS study FENtrepid, OCREVUS serves as the comparator, illustrating the current treatment landscape for primary progressive MS.

Global MS context: more than 2.9 million people live with MS; RMS accounts for about 85% of cases and PPMS about 15%, with OCREVUS as the only approved PPMS option previously.

Safety signals in RMS arms included liver enzyme elevations similar to teriflunomide, with asymptomatic Hyer's Law cases that resolved after stopping treatment; eight fatalities occurred in fenebrutinib arms and one in the teriflunomide arm, with ongoing analyses.

Across RMS trials, Hy's Law cases were asymptomatic and resolved after discontinuation, and there was no uptick in such cases beyond those initial instances.

Secondary endpoints showed reductions in brain MRI lesions and favorable trends in disability progression, signaling activity on both relapsing and progressive MS biology.

The RMS trials enrolled 1,497 adults in a double-blind design comparing fenebrutinib twice daily to teriflunomide once daily for at least 96 weeks, with an open-label extension after the double-blind phase.