1. BTK Inhibitors
Bruton tyrosine kinase (BTK) is an enzyme that plays a crucial role in the survival and function of B-cells. B-cells or B lymphocytes play a critical role in the pathogenesis of multiple sclerosis. By blocking BTK , these medications work by preventing their multiplication and actions. BTK is also associated with other immune cells like macrophages and microglia present in the brain which can play a role in worsening disability in progressive MS. Several BTK inhibitors were tested in clinical trials.
A specific one called Fenebrutinib has completed a phase 3 trial in primary progressive MS, and the results were recently reported February of 2026.
In this study of 985 adult patients with primary progressive multiple sclerosis, fenebrutinib was compared to ocrelizumab. Fenebrutinib showed a 12% reduction in the risk of disability progression compared to ocrelizumab, measured by the time composite confirmed disability progression. The composite confirmed disability progression (cCDP) incorporated three measures of disability – Expanded Disability Status Scale (EDSS), walking speed measured by the timed 25-foot walk and upper limb function measured by the nine-hole peg test.
Submission for FDA approval is expected first half of 2026
2. Frexalimab
Fexalimab is an anti-CD40L monoclonal antibody. CD40–CD40L pathway is vital for the interactions between T cells and B cells and other immune cells. Blocking this pathway results in decrease in downstream inflammation.
A Phase 2 trial of 129 MS patients showed that frexalimab had a positive effect reducing the number of new gadolinium-enhancing lesions when compared with placebo. There are 3 ongoing trials. One phase-3 trial in Secondary progressive MS is enrolling now
3. CAR-T Therapy
In this therapy T cells are collected from the patient after a blood draw. These cells are then sent to the manufacturer laboratories, where they are genetically engineered to have specific proteins on them called chimeric antigen receptors ( CARs). Then these are grown or multiplied so there is many of them. These modified T cells are then infused back to the patient. Prior to being infused to the patient the patient is treated with chemotherapy so that the immune system does not attack and kill the T cells the at are modified and infused back. Once the T cells are infused back into the patient. These T cells with the CARs can now latch on to the antigen ( targets) on the cells that they were created to “ attack”. In the patient these T cells multiple and circulate and kill the target cells. For MS, CAR-T cells are made to target B cells in the circulation and brain as well. CAR-T therapy has been mostly used in cancer until now, but after treatment in a few MS patients showed promising results, it’s currently in early clinical trials for MS including progressive forms.