- The preliminary results of the first of two clinical trials in relapsing MS showed that fenebrutinib reduced the rate of relapses in comparison to teriflunomide, an existing treatment for relapsing MS.
- The clinical trial in primary progressive MS showed that fenebrutinib was not inferior to ocrelizumab (an existing treatment for primary progressive MS) in delaying confirmed disability progression.
- These results will help guide future discussions with regulators to potentially provide a new treatment option for people with relapsing MS and people with primary progressive MS.
What is fenebrutinib?
Fenebrutinib is an experimental oral drug being studied for its ability to treat relapsing MS and primary progressive MS. It is in a class of medications known as Bruton’s tyrosine kinase (BTK) inhibitors. BTK is an enzyme (a biological molecule that speeds up reactions within cells) that is important for many immune “B cells” as well as immune cells in the brain and spinal cord, known as microglia.
This means that BTK inhibitors can target the immune cells that are thought to be involved in disease progression inside and outside the brain tissue. Additionally, because BTK inhibitors only target B cells that contain BTK, rather than all B cells, they do not compromise the overall immune system, offering a potentially safer and more targeted treatment than those currently available.
Fenebrutinib and relapsing MS – FENhance
There are two Phase III clinical trials with similar designs (called FENhance 1 and 2) for fenebrutinib in relapsing MS (RMS). Results from one of these trials, FENhance 2, was recently presented at the ECTRIMS Conference.
Over both studies, 1,497 participants will be treated over 96 weeks with either fenebrutinib or teriflunomide, an oral medication currently available to treat RMS. The early results from FENhance 2 showed that fenebrutinib significantly reduced the rate of relapses compared to teriflunomide. The sister clinical trial, FENhance 1, is expected to have results available in the first half of 2026. These trial results will then be combined to determine the ultimate outcome, including the full safety results.
Fenebrutinib and primary progressive MS – FENtrepid
There is currently only one medication on the market for primary progressive MS (PPMS). Due to the fact that they can penetrate the brain and spinal cord, there is hope that the BTK inhibitors, such as fenebrutinib will also be effective treatments in progressive forms of MS. Good early results released in the first week of November have justified this view, showing promising outcomes for fenebrutinib in a clinical trial of primary progressive MS.
The Phase III clinical trial of fenebrutinib in primary progressive MS was called FENtrepid and compared outcomes of participants on fenebrutinib with those on ocrelizumab, which is the only medication currently approved for primary progressive MS.
FENtrepid was designed as a “non-inferiority trial”, where the goal is not to prove that a new treatment is better (as in a traditional design), but rather that it is “not significantly worse” than an established treatment – within a pre-specified margin.
The results showed that fenebrutinib was non-inferior to ocrelizumab as measured by the delay in the onset of composite confirmed disability progression over a period of at least 120 weeks of treatment. The composite confirmed disability progression measure incorporates three measures of disability – total functional disability measured by the Expanded Disability Status Scale (EDSS), walking speed measured by the timed 25-foot walk (T25FW), and upper limb function measured by the nine-hole peg test (9HPT). It is considered more sensitive than EDSS and captures a wider range of disability.
The early results hint that fenebrutinib may perform better than ocrelizumab, however the trial was not designed to be able determine this definitively.
What does this mean for people with MS?
All three clinical trials of fenebrutinib had ambitious designs to compare the experimental drug with active treatments, rather than placebo (dummy tablets). This means that the experimental treatment must be at least as good as these comparator treatments which are currently available for people living with MS.
These are promising results, but fenebrutinib remains under clinical investigation, and its safety and effectiveness have not been evaluated by any regulatory authority. These results will serve as a foundation for future discussions with regulatory authorities. If these discussions are positive, then fenebrutinib may provide a new treatment option for people with relapsing MS and people with primary progressive MS.
