Berlin, Germany – March 4, 2026 – In a significant advancement for the treatment of multiple sclerosis (MS), Roche announced today positive results from the Phase III FENhance 1 trial evaluating fenebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, in individuals with relapsing multiple sclerosis (RMS). The trial demonstrated a statistically significant 51% reduction in the annualized relapse rate (ARR) compared to teriflunomide, a commonly prescribed MS medication, after a minimum of 96 weeks of treatment. This builds upon earlier positive data from the FENhance 2 trial in RMS and the FENtrepid trial in primary progressive MS (PPMS), positioning fenebrutinib as a potential new therapeutic option for both forms of the disease.
Multiple sclerosis is a chronic, often disabling disease that affects the central nervous system – the brain and spinal cord. RMS, the most common form of MS, is characterized by periods of new or worsening symptoms (relapses) followed by periods of recovery. PPMS, a less common but often more severe form, involves a gradual worsening of neurological function from the onset, without distinct relapses or remissions. Current treatments aim to manage symptoms and slow disease progression, but a need remains for more effective therapies, particularly those that address both relapsing and progressive forms of MS.
Fenebrutinib Demonstrates Significant Efficacy Across Trials
The FENhance 1 trial, a randomized, double-blind, multi-center study, involved 1,497 adults diagnosed with RMS. Participants were assigned to receive either oral fenebrutinib twice daily or oral teriflunomide once daily for at least 96 weeks. The primary endpoint of the trial, the ARR, was significantly reduced in the fenebrutinib group, showcasing a 51% improvement over teriflunomide. This finding aligns with the results from the FENhance 2 trial, which reported a 59% reduction in ARR. According to Roche, these combined results suggest that fenebrutinib could potentially reduce relapses to approximately one every 17 years.
Beyond the reduction in relapse rates, both the FENhance 1 and FENhance 2 studies observed statistically significant reductions in brain lesions, as measured by magnetic resonance imaging (MRI). These lesions are indicative of inflammatory activity in the brain and spinal cord, and their reduction suggests that fenebrutinib may have a disease-modifying effect. All progression endpoints also showed favorable trends for fenebrutinib, indicating a potential to slow the accumulation of disability over time. The secondary endpoints evaluated included the overall count of T1-gadolinium-enhancing MRI lesions, the sum of new or enlarged T2-weighted MRI lesions, and the time to confirmed disability progression.
Understanding BTK Inhibition in MS
Fenebrutinib works by selectively inhibiting Bruton’s tyrosine kinase (BTK), an enzyme involved in the signaling pathways of immune cells, including B cells, and microglia. In MS, these cells play a role in the inflammatory processes that damage the myelin sheath, the protective covering of nerve fibers. By blocking BTK, fenebrutinib aims to dampen the immune response and reduce inflammation in the central nervous system. What sets fenebrutinib apart is its ability to penetrate the brain, allowing it to directly target inflammatory processes within the central nervous system. This brain penetration is a key feature, as many existing MS therapies have limited access to the brain.
Safety Considerations and Regulatory Pathway
Even as the trial results are promising, it’s important to note that safety data is continuously evaluated. Roche reported that fatal cases occurred during the trials, with eight reported in the fenebrutinib arm and one in the teriflunomide arm. Further investigations are underway to determine the cause of these fatalities and assess the overall safety profile of the drug.
Roche plans to submit the comprehensive data from the FENhance 1, FENhance 2, and FENtrepid trials to regulatory authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), seeking approval for fenebrutinib as a treatment for both RMS and PPMS. If approved, fenebrutinib could become the first high-efficacy oral treatment specifically designed for both relapsing and progressive forms of MS, offering a significant advancement for individuals living with this challenging condition.
Levi Garraway on the Potential of Fenebrutinib
Levi Garraway, Roche’s chief medical officer and global head of product development, emphasized the potential impact of fenebrutinib. “These pivotal results, together with the earlier data, provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for RMS and PPMS,” he stated in a press release. “Building on a decade of transforming MS treatment, we are committed to advancing innovation to one day allow people with MS to live a life without disability.”
Looking Ahead: Roche’s Broader Research in Neurodegenerative Diseases
The positive results with fenebrutinib represent a broader commitment by Roche to developing innovative therapies for neurological diseases. In January 2026, the company also reported positive topline results from a Phase II trial evaluating CT-388, a once-weekly subcutaneous injection, for obesity. This demonstrates Roche’s expanding focus on addressing significant unmet medical needs across a range of conditions affecting the nervous system and metabolic health.
The development of fenebrutinib offers renewed hope for individuals with MS, potentially providing a more effective and convenient treatment option. The coming months will be crucial as Roche submits its data to regulatory agencies and works towards making this promising therapy available to patients. Further research will continue to refine our understanding of BTK inhibition and its role in managing MS and other neuroinflammatory conditions.
What’s next? Roche is preparing to submit the complete data package to regulatory authorities for review. A decision on approval is anticipated in late 2026 or early 2027. Stay informed about the latest developments in MS research and treatment options by visiting the National Multiple Sclerosis Society website: https://www.nationalmssociety.org/. We encourage readers to share their thoughts and experiences with MS in the comments below.