The multiple sclerosis (MS) therapeutic pipeline is robust, featuring over 80 active therapies under development by more than 75 companies, according to a recent DelveInsight report. These emerging treatments aim to address unmet needs in MS, a chronic autoimmune disorder affecting the central nervous system. The pipeline includes a variety of approaches, from disease-modifying therapies (DMTs) to symptomatic treatments, offering hope for improved patient outcomes.
Clinical Trial Updates and Regulatory Milestones
Several companies have recently announced updates from their clinical trials. In September 2024, Sanofi reported mixed results from Phase III trials of its investigational oral brain-penetrant BTK inhibitor, tolebrutinib. The HERCULES trial met its primary endpoint in individuals with non-relapsing secondary progressive MS (nrSPMS), while the GEMINI trials did not. Immunic, Inc. announced a positive outcome of the non-binding, interim futility analysis of its Phase III ENSURE program, investigating lead asset, nuclear receptor related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), for the treatment of relapsing multiple sclerosis (RMS). Based on the outcome of the interim futility analysis, an unblinded Independent Data Monitoring Committee (IDMC) has recommended that the trials are not futile and should continue as planned.
Roche secured FDA approval for an injectable form of its MS treatment, Ocrevus, in September 2024, potentially reducing patient treatment time. Abata Therapeutics received Fast Track designation from the FDA for ABA-101 for progressive MS in August 2024, and TG Therapeutics' IND application for azercabtagene zapreleucel (azer-cel), an allogeneic CAR-T therapy, was cleared by the FDA for a Phase 1 trial in progressive MS, also in August 2024. Kyverna Therapeutics, Inc. announced it received fast-track designation by the U.S. Food and Drug Administration (FDA) for its autologous, fully human CD19 chimeric antigen receptor (CAR) T-cell product candidate, KYV-101, to be used for the treatment of multiple sclerosis (MS) in January 2024.
Emerging Therapies and Mechanisms of Action
The MS pipeline features a diverse range of therapeutic modalities. Monoclonal antibodies, such as BCD-132 (Biocad), are being developed to target specific immune cells involved in MS pathogenesis. Oral therapies, including remibrutinib (Novartis) and tolebrutinib (Sanofi), offer convenient administration and the potential to penetrate the blood-brain barrier. Clene Nanomedicine is investigating CNM-Au8, an oral drug designed to stimulate energy metabolism and modulate the immune system. CAR-T cell therapies, such as azercabtagene zapreleucel (TG Therapeutics) and KYV-101 (Kyverna Therapeutics), represent a novel approach to selectively deplete autoreactive immune cells. Other notable pipeline candidates include GA Depot (Mapi Pharma), IMU 838 (Immunic), NeuroVax (Immune Response BioPharma), Orelabrutinib (InnoCare Pharma), Vafidemstat (Oryzon Genomics), and Lucid-MS (Lucid Psycheceuticals).
Route of Administration and Molecule Types
The emerging MS therapies are being developed for various routes of administration, including oral, intravenous, subcutaneous, and intramuscular delivery. Molecule types in the pipeline include monoclonal antibodies, small molecules, peptides, polymers, and gene therapies, reflecting the diverse approaches being pursued to tackle MS.
Multiple Sclerosis: An Overview
Multiple sclerosis is a chronic autoimmune disorder affecting the central nervous system, leading to the deterioration or permanent damage of myelin, the protective sheath surrounding nerve fibers. While the exact cause of multiple sclerosis remains unclear, it is believed to involve a combination of genetic predisposition, environmental factors, and possibly viral infections. Common symptoms of multiple sclerosis include fatigue, difficulty walking, numbness or tingling in the limbs, muscle weakness, and vision problems, which can vary significantly among individuals and may evolve over time.
