Researchers are continuing to explore new treatment options for multiple sclerosis, especially for progressive forms of the disease where effective therapies remain limited. One promising area of research involves BTK inhibitors, oral medications designed to reduce harmful immune activity both in the body and within the brain and spinal cord. Two BTK inhibitors that have received a lot of attention are tolebrutinib and fenebrutinib. Here’s what we know right now.
Tolebrutinib: What Happened and Why It Still Matters
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Tolebrutinib, developed by Sanofi, was studied in people with relapsing, non-relapsing secondary progressive, and primary progressive MS. In clinical trials, the medication showed an ability to slow disability progression in non-relapsing secondary progressive MS, an important outcome for people whose MS continues to worsen even without relapses.
Because of these results, there was hope that tolebrutinib could become one of the first treatments specifically targeting progression driven by ongoing inflammation in the brain. However, in December, the U.S. Food and Drug Administration (FDA) declined to approve the drug. The FDA cited concerns about whether the benefits clearly outweighed the risks, with particular attention to liver safety.
This decision was disappointing for many in the MS community. While tolebrutinib is not currently available in the U.S., its clinical trials helped advance understanding of progressive MS and provided valuable insights into how targeting brain-based inflammation might slow disability over time. Sanofi has indicated it will continue discussions with regulators about potential next steps.
Fenebrutinib: Why There Is Ongoing Hope
Fenebrutinib, developed by Genentech, is another BTK inhibitor that works in a slightly different way and is still being studied in large clinical trials. Unlike tolebrutinib and previously evobrutinib, fenebrutinib remains on track in development and has shown encouraging results across multiple types of MS.
So far, studies suggest fenebrutinib may:
- Reduce relapses and new MRI activity in people with relapsing MS
- Slow disability progression in people with primary progressive MS, with results comparable to ocrelizumab
- Offer the convenience of an oral treatment, rather than an infusion
- Maintain a generally consistent safety profile so far with liver safety monitoring in place.
Because fenebrutinib is still under review, it is not yet approved, but many in the MS community see it as one of the most hopeful potential oral treatments currently in development. Clinical trial study results are anticipated to be shared at the upcoming ACTRIMS conference in February for the progressive trial and at the American Academy of Neurologists (AAN) in April for the relapsing trials. We will continue to keep you informed.
Why This Research Is Important
For many people with MS, especially those with progressive disease, current treatments do not fully address gradual disability worsening. BTK inhibitors are being studied because they may reduce chronic inflammation inside the brain, which is believed to play a major role in progression.
Although the FDA’s rejection of tolebrutinib was a setback, it does not close the door on this entire class of medications. Fenebrutinib and other BTK inhibitors continue to move forward, offering hope that future treatments could better slow progression and preserve function.
