Genentech'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)

Core Insights - Genentech announced that the pivotal Phase III study (FENhance 1) of fenebrutinib in relapsing multiple sclerosis (RMS) met its primary endpoint, showing a 51% reduction in annualized relapse rate (ARR) compared to teriflunomide over at least 96 weeks of treatment [1][3] - The results from FENhance 1 are consistent with FENhance 2, which showed a 59% reduction in ARR, indicating a profound benefit on relapsing and progressive disease biology [1][3] - Secondary endpoints in both RMS studies demonstrated statistically significant reductions in brain lesions, with favorable trends observed in all progression endpoints for fenebrutinib [1][3] Study Details - FENhance 1 and 2 are Phase III multicenter, randomized, double-blind studies involving 1,497 adult patients with RMS, comparing fenebrutinib to teriflunomide [7] - Participants were randomized 1:1 to receive either oral fenebrutinib twice daily or oral teriflunomide once daily for at least 96 weeks [7] - The primary endpoint was ARR, while secondary endpoints included MRI lesion counts and measures of disability progression [8] Safety and Efficacy - Liver transaminase elevations in both RMS studies were comparable to teriflunomide, with one Hy's Law case reported in each treatment arm, both of which were asymptomatic and resolved after discontinuation [4] - A total of 1 fatal case was reported in the teriflunomide arm, while 8 fatal cases occurred in the fenebrutinib arms, with further analyses ongoing to understand these findings [5] - Fenebrutinib targets B cells and microglia to control acute inflammation and address chronic damage, designed to have high potency and selectivity [6][11][12] Future Developments - Full data from the FENhance 1 and 2 studies will be presented at the American Academy of Neurology (AAN) Annual Meeting in 2026 and submitted to regulatory authorities alongside data from the FENtrepid study [2]