A research emphasis on measuring relapses and tracking MRIs naturally leads to a treatment emphasis on preventing relapses and reducing MRI activity. And of course, both are still important.
But the larger shifts in focus to broader, more patient-centered research has over time brought attention to MS progression — how to stop the slow, steady changes that continue to impact people living with MS even if relapses and activity stop. And that shift is driving the next generation of MS therapies.
Among investigational therapies, Bruton’s tyrosine kinase (BTK) inhibitors are drawing attention because they target B cells and microglia — cells linked to both inflammation and long term neurodegeneration. These types of drugs are already available for the treatment of B-cell cancers, but a new generation of medications with fewer side effects are being studied for the treatment of MS.
In simple terms, BTK inhibitors aim to reduce activity not only in the bloodstream (like traditional immune therapies), but also within the central nervous system, where slow “smoldering” inflammation can drive progression over time.
Recent studies of BTK inhibitors in MS are ongoing, but have reported encouraging signs in potentially slowing disability progression.
Tolebrutinib, a BTK inhibitor expected to be the first available to the public, is under review by the FDA with priority status, but the agency recently extended its decision deadline to December 28, 2025 to evaluate new analyses submitted during review. That delay doesn’t necessarily indicate a problem with the findings, and it’s not uncommon for MS drug approvals to be slightly delayed by the FDA. It does reflect the caution regulators take with new drugs that affect immune cells in the brain.
At the end of November, we also heard the topline results for another BTK inhibitor — fenebrutinib. There were few details, but fenebrutinib reduced relapses more than teriflunomide in relapsing MS with a similar trial due to report in early 2026. Additionally, fenebrutinib was non-inferior compared to ocrelizumab in the treatment of primary progressive MS meaning that statistically, they could not see a difference between the two drugs.
The bottom line: at press time for this issue, BTK inhibitors are not yet approved for MS in the U.S., but they’re likely coming very soon. And if ongoing results continue to be positive, more BTKi options may join the landscape quickly — options designed not only to prevent relapses, but to address progression directly.
