The newest FDA-approved drug for multiple sclerosis (MS) is expected to be **tolebrutinib**, an oral Bruton’s tyrosine kinase (BTK) inhibitor designed specifically for treating *non-relapsing secondary progressive multiple sclerosis* (SPMS). This drug represents a significant advancement because it targets the chronic inflammation that drives disability progression in MS independently of relapses, which has been a major unmet need in MS treatment.
Tolebrutinib works by blocking BTK, an enzyme essential for activating immune cells such as B cells and microglia. These cells play a central role in the autoimmune and inflammatory processes that damage the nervous system in MS. Unlike many existing therapies that mainly target peripheral immune cells, tolebrutinib can penetrate the brain, allowing it to directly affect immune activity within the central nervous system. This ability to cross the blood-brain barrier is crucial because it addresses inflammation inside the brain and spinal cord, which is thought to contribute to progressive disability in MS.
Clinical trials, including the Phase 3 HERCULES study, have shown that tolebrutinib significantly reduces the risk of confirmed disability progression sustained for at least six months in adults with non-relapsing SPMS compared to placebo. In this trial, fewer patients treated with tolebrutinib experienced disability progression, indicating its potential to slow the worsening of neurological function even when relapses are not occurring.
The FDA has granted tolebrutinib both Breakthrough Therapy designation and Priority Review status, reflecting the drug’s potential to address a critical gap in MS treatment. A regulatory decision by the FDA was anticipated by late September 2025. Notably, the United Arab Emirates has already approved tolebrutinib for non-relapsing SPMS, making it the first country to do so.
This approval would mark tolebrutinib as the first BTK inhibitor approved for MS and the first therapy specifically indicated for non-relapsing SPMS. This is a major milestone because secondary progressive MS, especially the non-relapsing form, has been historically difficult to treat, with few effective options available.
In addition to tolebrutinib, other recent developments in MS treatment include the availability of generic versions of existing drugs like Zeposia (ozanimod), which is approved for relapsing forms of MS, and ongoing research into oral therapies such as MAVENCLAD (cladribine) that offer durable effects without continuous immunosuppression. However, tolebrutinib stands out as a novel mechanism targeting both peripheral and central immune cells to slow progression in a form of MS that previously lacked effective treatments.
In summary, tolebrutinib is poised to become the newest FDA-approved drug for MS, specifically targeting non-relapsing secondary progressive MS by inhibiting BTK and addressing central nervous system inflammation, potentially changing the treatment landscape for this challenging stage of the disease.
