Experimental BTK Inhibitor Suppressed Inflammatory Disease Activity in Those with Relapsing MS

Fenebrutinib (Roche, Basel, Switzerland), an investigational oral, reversible noncovalent Bruton tyrosine kinase (BTK) inhibitor, demonstrated significant efficacy in suppressing inflammatory disease activity in people with relapsing multiple sclerosis (RMS) according to the results of the open-label extension (OLE) of the phase 2 FENopta study (NCT05119569). The results, presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, also showed that fenebrutinib, which targets both peripheral and central nervous system inflammation, maintained a favorable safety profile and robust patient retention throughout the OLE.

The OLE enrolled 99 people with RMS who received fenebrutinib (n=65) or placebo (n=34) during the initial double-blind treatment period. All participants transitioned to fenebrutinib in the OLE, and 96% remained in the study through week 48. Disease activity was assessed from a review of protocol-defined clinical relapses and brain MRI studies.

At OLE week 48, results showed:

• 96% of participants were relapse-free, with an annualized relapse rate of .04.
• The average change from baseline on the Expanded Disability Status Scale (EDSS) was 0, and 89.6% of participants had no evidence of disease activity-3.
• 99% of participants were free of new T1 gadolinium-enhancing lesions, and the average number of new gadolinium-enhancing lesions was .015 lesions per scan (n=67).
• The adjusted annualized rate of new and enlarging T2 lesions was .13 for participants who switched to fenebrutinib from placebo (95% CI, .022 to .78) and .16 for those who were randomized to fenebrutinib in the double-blind period (95% CI, .044 to .60).
• T2 lesion volume decreased toward baseline in those who switched from placebo (.03 cm³; 95% CI, -.28 to .35) and further improved in those who were initially randomized to fenebrutinib (-.33 cm³; 95% CI, -.57 to -.095).
• One participant experienced serious adverse events (urinary tract infection and nephrolithiasis), while 1 other participant developed an elevation of asymptomatic alanine transaminase that resolved with treatment termination.

Researchers concluded that 1 year of  fenebrutinib treatment resulted in near-complete suppression of acute inflammatory disease activity, supporting its potential as a treatment for MS. Three ongoing phase 3 clinical trials are assessing fenebrutinib’s clinical utility and impact on relapsing and progressive MS.