Experimental therapy may curb chronic brain inflammation in MS

Genentech’s experimental oral therapy fenebrutinib may help control the chronic inflammation in the brain associated with disability progression in both relapsing forms of multiple sclerosis (MS) and primary progressive MS (PPMS).

That’s according to new analyses of data from three ongoing Phase 3 trials, in which fenebrutinib was associated with significant reductions in slowly expanding lesions in people with both forms of MS. In those with relapsing MS, treatment also significantly reduced relapses, brain tissue loss, and slowed disability progression compared with Aubagio (teriflunomide), an approved MS treatment.

“Our recent data indicate that fenebrutinib can inhibit disease activity inside and outside the central nervous system [brain and spinal cord], underscoring its potential to transform care for people living with relapsing and primary progressive forms of multiple sclerosis,” Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of global product development, said in a company press release.

The findings are being presented at MSToronto2026, the joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, being held Oct. 21–23 in Toronto.

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MS occurs when the body’s immune system mistakenly attacks and damages healthy tissue in the brain and spinal cord, causing inflammation and nerve damage that lead to MS symptoms. Relapsing MS is marked by periods of new or worsening symptoms, called relapses, followed by periods of remission when symptoms ease. In PPMS, symptoms worsen gradually from the onset of the disease.

Although more than 20 disease-modifying therapies are approved for MS, most are specifically indicated for relapsing forms of the disease. These treatments primarily suppress acute inflammatory activity that drives relapses and new brain lesions. However, they are generally less effective at addressing the smoldering inflammation inside the brain that contributes to gradual disease progression over time.

“Addressing long-term disability progression to preserve people’s independence remains a critical challenge in neuroinflammatory diseases, and particularly in multiple sclerosis,” Garraway said.

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Fenebrutinib shows positive results in 2 forms of MS

Fenebrutinib is designed to block Bruton’s tyrosine kinase, an enzyme involved in the activation of immune cells known to contribute to MS. The investigational therapy specifically targets circulating immune B-cells that drive MS relapses, but can also enter the brain and spinal cord, where it may act on microglia, immune cells involved in fueling chronic inflammation.

The treatment is being evaluated in three Phase 3 clinical trials. The FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) twin studies tested fenebrutinib against Aubagio in nearly 1,500 adults with relapsing forms of MS. In the FENtrepid study (NCT04544449), fenebrutinib was tested against the approved treatment Ocrevus (ocrelizumab) in adults with PPMS.

Recently reported findings showed that fenebrutinib reduced relapse rates by more than 50% compared with Aubagio in both FENhance trials and was at least as effective as Ocrevus at slowing disability progression in FENtrepid.

Data from the latest analyses reinforce the potential of fenebrutinib as the first and only high-efficacy oral medicine for both forms of MS, Genetech said.

Across the three trials, researchers examined slowly expanding lesions (SELs), areas of existing brain damage that gradually grow over time. Unlike new lesions that form during acute inflammatory activity, SELs are thought to reflect ongoing inflammation in the brain.

Fenebrutinib significantly reduced the volume of these lesions by up to 30% compared with the control treatments. The analyses covered 96 weeks, or nearly two years, in the FENhance trials, and 120 weeks, or about 2.3 years, in FENtrepid.

Therapy outperformed Aubagio in reducing annual brain volume loss

Researchers also looked at another marker of chronic inflammation in the FENhance trials: paramagnetic rim lesions (PRLs). These are areas of brain damage seen on MRI scans that are linked to chronic inflammation. Among people with relapsing forms of MS, fenebrutinib significantly reduced the accumulation of PRLs by 62% compared with Aubagio.

The new analyses also provided a broader picture of fenebrutinib’s effects on relapsing MS. The new analysis combining data from both FENhance trials showed that fenebrutinib reduced relapse rates by 55% and annual brain volume loss by 23% compared with Aubagio.

The experimental oral therapy also significantly lowered the risk of confirmed disability progression by 16%, based on a combined measure assessing neurological disability, walking ability, and hand function.

Looking at disease activity, 75% of fenebrutinib-treated patients had no evidence of disease activity, known as NEDA-3, at nearly two years. This means they had no relapses, no new MRI disease activity, and no confirmed disability worsening during the assessment period. Compared with Aubagio, fenebrutinib reduced the risk of experiencing disease activity by 70%, a statistically significant difference.

Genentech’s application seeking approval of fenebrutinib for both forms of MS is currently under priority review by the U.S. Food and Drug Administration. This process shortens the agency’s target review timeline from 10 months to six months. A decision is expected by late March or early April 2027.