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Hot Topics in MS: Tyrosine Kinases Inhibitors Studied for Treatment of MS

A whole new family of drugs is currently being studied very aggressively for the treatment of MS: Tyrosine kinases Inhibitors.

Tyrosine kinases (TYKs) are intracellular enzymes that play a key role in numerous processes that control cell proliferation and differentiation. They regulate cell growth and cellular metabolism and promote cell survival as well as programmed cell death. Tyrosine kinase inhibitors is a class of drugs that have been used in cancer therapies, the rheumatological realm of diseases, and are now being explored for use in the MS.

Tyrosine kinase inhibitors work by inhibiting enzymes to reduce the activation of B cells, immune cells that play a role in MS. There are two subtypes of Tyrosine kinase inhibitors being studied in MS: Masitinib and Bruton’s tyrosine kinase inhibitors. Masitinib target mast cells, macrophages, and microglia which are all part of the innate immune system. Microglia are particularly important because they are the only immune cells that live inside the nervous system.

Bruton’s tyrosine kinases (BTK) are enzymes on many different blood-based cells, except for T cells, natural killer cells, and plasma cells. BTKs are more widely used throughout the blood system, but especially within B cells. BTKs are also utilized in the microglia inside the nervous system. Microglia seem to be much more important for Progressive MS and are associated with a significant degree of B cell activation in autopsy in individuals with MS. BTK inhibitors (BTKi) work by reducing activation of B cells in a targeted way.

The great hope with this class of medications is that they will be useful in turning down the different types of inflammatory events that are going on in those individuals with Progressive MS, for which there is the greatest unmet need in the treatment of MS.

Currently, there are several Phase 3 clinical trials happening to study multiple different Masitinib and BTKi drugs for the treatment of relapsing remitting MS and progressive MS. A small Phase 2 study and recent Phase 3 study published earlier this year examined Masitinib and showed that the drug decreased progression of disability in Progressive MS patients.

The BTKi drugs currently being studied include evobrutinib, tolebrutinib*, and tenebrutinib. A Phase 2 study of evobrutinib showed a significant impact in reducing number of relapses in relapsing MS patients. And a separate Phase 2 study of evobrutinib in progressive MS showed a substantial impact on reducing the number of slowly expanding lesions in progressive MS patients.

A number of studies are ongoing to explore BTKi drugs as a potentially significant new frontier in effectively treating both relapsing and progressive MS. n
Editor’s Note: One Tolebrutnib study was recently paused out of an abundance of caution after some participants experienced liver damage. It’s not yet clear whether or when that study will resume.

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