Genentech, a member of the Roche Group, has announced positive results from the first of two phase 3 trials investigating fenebrutinib, the first and only Bruton’s tyrosine kinase (BTK) inhibitor in development for the treatment of relapsing multiple sclerosis (RMS).
Multiple sclerosis (MS) is a chronic neurological condition affecting more than 2.9 million people globally. Approximately 85% of patients are diagnosed with RMS, which is characterised by relapses and progressive disability over time. The remaining 15% have primary progressive multiple sclerosis (PPMS), a form marked by continuous worsening of symptoms without relapses or remissions. Currently, the only treatment approved by the US Food and Drug Administration (FDA) for PPMS is Ocrevus (ocrelizumab).
Fenebrutinib is an investigational, oral BTK inhibitor that targets both B cells and microglia in the immune system. This dual mechanism of action is designed to address key drivers of MS pathology: B-cell inhibition helps to control the acute inflammation responsible for relapses, while targeting microglia within the central nervous system may limit chronic damage and slow long-term disability progression.
According to Genentech, fenebrutinib’s high potency, selectivity and reversibility are driven by its non-covalent binding properties, distinguishing it from other treatments currently in development.
Results from the randomised, double-blind, double-dummy, parallel-group FENhance 2 study showed that fenebrutinib met its primary endpoint, significantly reducing the annualised relapse rate (ARR) in patients with RMS compared with teriflunomide over 96 weeks of treatment. Results from FENhance 1, the second phase 3 trial in the RMS programme, are expected in the first half of 2026.
In addition, the phase 3 FENtrepid study, which evaluated fenebrutinib versus Ocrevus in patients with PPMS, also met its primary endpoint. Fenebrutinib demonstrated non-inferiority to Ocrevus in delaying the onset of composite confirmed disability progression over the treatment period.
“Fenebrutinib substantially reduced the number of relapses in RMS and slowed disability progression in PPMS. These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine as the first high-efficacy, oral treatment for people with RMS or PPMS,” said Levi Garraway, Genentech’s chief medical officer and head of Global Product Development.
“Therefore, these pivotal results for fenebrutinib may offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community.”