Reviewed by Sarim Mir, MD — Board-Certified Neurologist, Mir Neurology (Hagerstown & Cumberland, MD)
Key takeaways
- BTK (Bruton’s tyrosine kinase) inhibitors are a new class being studied for progressive multiple sclerosis (MS), a form that has been hard to treat.
- Roche’s fenebrutinib met its primary endpoint in the Phase III FENtrepid study, showing non-inferiority to ocrelizumab (Ocrevus) in primary progressive MS.
- Sanofi’s tolebrutinib received an FDA Complete Response Letter (CRL) for non-relapsing secondary progressive MS, largely over liver-safety concerns.
- Both drugs remain investigational for these progressive-MS uses — neither is FDA-approved for them today.
- The takeaway is cautious optimism: one program advanced, another stalled, and longer-term data are still being reviewed.
What changed
Progressive MS — where disability slowly accumulates even without obvious relapses — has long lacked good treatment options. A newer class of oral drugs called BTK inhibitors is now being tested to fill that gap. In early 2026, two of these programs reached very different milestones, and it is worth understanding both, because together they show where this science stands honestly.
Plain-English explainer
BTK stands for Bruton’s tyrosine kinase, an enzyme that helps drive immune-cell activity, including inside the brain and spinal cord. In MS, much of the damage in progressive disease seems to come from immune activity “behind” the blood-brain barrier. The hope with BTK inhibitors is that, because they are small molecules that can cross into the central nervous system, they may calm this smoldering inflammation in a way older drugs cannot.
It is important to be clear: this is a promising mechanism, not a finished story. These medicines are still investigational for progressive MS. They are not cures, and they are not yet FDA-approved for the progressive uses described here.
How it works / detail
Here is the honest “what advanced versus what stalled.”
What advanced — fenebrutinib (Roche). In the Phase III FENtrepid study, fenebrutinib met its primary endpoint of non-inferiority to ocrelizumab (brand name Ocrevus) in slowing disability progression in primary progressive MS. The trial randomized roughly 985 people to either oral fenebrutinib or intravenous ocrelizumab. Roche described it as the first investigational medicine in over a decade to reduce disability progression in primary progressive MS. That is meaningful, but “non-inferior” means it performed comparably to an existing therapy, not that it was dramatically better. Roche has indicated that data from its Phase III fenebrutinib program will be submitted to regulators after additional studies read out.
What stalled — tolebrutinib (Sanofi). Tolebrutinib, another BTK inhibitor, received an FDA Complete Response Letter (CRL) for non-relapsing secondary progressive MS. A CRL means the FDA is not approving the application in its current form. Reporting tied the concerns largely to liver safety. A CRL is not necessarily the end of a drug’s story, but it does mean tolebrutinib is not available for this use now, and questions must be addressed first.
The practical message: BTK inhibitors are an exciting direction with genuine momentum, but they are also a reminder that safety and regulatory review matter. Encouraging trial results and FDA approval are not the same thing.
What this means for you in Hagerstown & Cumberland
If you or a loved one has progressive MS, it is natural to ask about every new option. At Mir Neurology, we follow this research closely and can explain what is FDA-approved and available today versus what is still in trials. We will help you weigh the realistic options for your situation across Western Maryland. Learn more about our multiple sclerosis care.
Call (301) 797-7600 to request an appointment or request an appointment online.
Frequently asked questions
Can I get a BTK inhibitor for my progressive MS right now? For the progressive-MS uses discussed here, these drugs are still investigational and not FDA-approved. Availability may be limited to clinical trials. Your neurologist can review whether any trial or approved alternative fits your situation.
Is fenebrutinib better than Ocrevus? In the FENtrepid study, fenebrutinib was shown to be non-inferior to ocrelizumab in primary progressive MS — meaning comparable, not clearly superior. One potential difference is that fenebrutinib is taken orally, while ocrelizumab is an infusion. Regulatory review is ongoing.
Why was tolebrutinib not approved? The FDA issued a Complete Response Letter for its non-relapsing secondary progressive MS application, with reporting pointing to liver-safety concerns. A CRL means the drug is not approved in its current form for that use, though the program may continue.
This article is for general educational purposes and is not a substitute for individualized medical advice. The therapies discussed are investigational for the progressive-MS uses described and are not FDA-approved for them. No outcome is guaranteed.
Sources: Roche: fenebrutinib reduces disability progression in PPMS, Tolebrutinib Receives FDA CRL for Nonrelapsing Secondary Progressive MS (Pharmacy Times)
Need to talk to a neurologist about this?
Mir Neurology offers same-week appointments in Hagerstown & Cumberland, MD. No referral needed for most plans.
