1-year fenebrutinib curbs nearly all disease activity in relapsing MS trial
Phase 3 trials testing fenebrutinib’s potential for relapsing, progressive MS
A year of treatment with the experimental BTK inhibitor fenebrutinib was safe and nearly entirely suppressed signs of disease activity, including relapses, disability progression, and brain lesions, in people with relapsing forms of multiple sclerosis (MS), according to new data from the open-label extension part of a Phase 2 trial.
Roche, which is developing fenebrutinib through its subsidiary Genentech, now plans to present the data in more detail at the upcoming Congress of the European Committee for Treatment and Research in Multiple Sclerosis, being held in Copenhagen later this month.
Ongoing Phase 3 trials are further evaluating fenebrutinib’s potential in people with relapsing and progressive forms of MS, with data from these programs expected by the end of 2025.
“After a year of treatment, our BTK inhibitor fenebrutinib was able to suppress nearly all disease activity and disability progression in people with multiple sclerosis,’’ Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a company press release. “If these results are validated in the ongoing Phase III trials, fenebrutinib could further advance the treatment landscape for people living with multiple sclerosis.”
Fenebrutinib belongs to a class of therapeutics called BTK inhibitors. As the name suggests, these oral small molecules block the activity of the BTK enzyme, which controls how immune cells that are implicated in driving MS-related inflammation grow, survive, and become activated.
Fenebrutinib may help ease inflammation, prevent nerve damage in MS
By blocking BTK, fenebrutinib is expected to ease inflammation and prevent nerve damage in people with MS. Other BTK inhibitors that have been tested in MS include tolebrutinib and evobrutinib.
The Phase 2 FENopta trial (NCT05119569) evaluated fenebrutinib’s safety and efficacy in 109 adults, ages 18-55, with relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Participants were randomly assigned to receive either twice-daily oral fenebrutinib (200 mg) or a placebo for 12 weeks (about three months).
Results showed the treatment reduced the number of inflammatory brain lesions on MRI scans by 90% relative to a placebo after three months, meeting the study’s main goal. The total number of new or enlarging brain lesions was also significantly reduced, by 95%, compared with the placebo.
Moreover, data suggested the treatment can enter the brain and spinal cord at levels expected to sufficiently block immune cell activity.
After the first three months, 99 participants opted to enter an open-label extension phase, where all are continuing to receive daily fenebrutinib for up to around 3.5 years. New data from this extension period showed 96% of treated patients were free from relapses after 48 weeks (nearly a year). The overall annualized relapse rate over that year was 0.04.
Patients also did not experience any disability progression, as assessed by the Expanded Disability Status Scale.
At 48 weeks, 99% of patients were free from active inflammatory lesions
MRI data continued to show fenebrutinib suppressed disease activity in the brain. At 48 weeks, 99% of patients were free from active inflammatory lesions. In addition, total lesion burden was reduced by three times over this period relative to the end of the main trial.
Fenebrutinib’s safety profile was consistent with earlier reports. The most common side effects were urinary tract infection, COVID-19, and sore throat. One person had a rise in liver enzymes that resolved when treatment was discontinued.
Among the ongoing Phase 3 trials are the FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) studies, which are collectively testing fenebrutinib’s ability to reduce relapse rates compared with the approved therapy Aubagio (teriflunomide) in around 1,500 people with relapsing forms of MS.
Another Phase 3 trial, called FENtrepid (NCT04544449), is comparing fenebrutinib’s ability to slow disease progression in people with primary progressive MS relative to Ocrevus (ocrelizumab), the only treatment currently approved in the U.S. for this form of MS.
Notably, these Phase 3 studies were placed on a partial hold by U.S. regulators in November after two treated patients showed signs of possible treatment-related liver injury. The trials continued, but new enrollment was stopped at U.S. sites for all three studies.
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