The latest clinical trials for **progressive multiple sclerosis (MS)** focus on novel therapies targeting neuroinflammation, immune modulation, and neuroprotection, as well as non-pharmacological interventions. Progressive MS, which includes primary progressive MS (PPMS) and secondary progressive MS (SPMS), is characterized by gradual worsening of neurological function and currently has fewer effective treatment options compared to relapsing forms of MS. Recent trials aim to fill this gap with innovative approaches.
One of the most advanced drug candidates in late-stage trials is **vidofludimus calcium**, an oral immunomodulatory agent that inhibits dihydroorotate dehydrogenase (DHODH), an enzyme involved in immune cell proliferation. Vidofludimus calcium is undergoing two large Phase 3 studies named ENSURE-1 and ENSURE-2, enrolling over 2,000 patients with progressive MS. This drug has recently secured a U.S. patent specifically covering its use in progressive MS at doses between 10 and 45 mg daily, which is expected to protect its use through at least 2041. The drug’s mechanism targets immune pathways thought to contribute to disease progression, potentially slowing disability accumulation in progressive MS patients.
Another promising therapy under investigation is **ibudilast (MN-166)**, an oral phosphodiesterase inhibitor with anti-inflammatory and neuroprotective properties. Ibudilast modulates neuroinflammation by inhibiting glial cell activation, which is believed to play a role in progressive MS pathology. The COMBAT-ALS trial, although primarily focused on amyotrophic lateral sclerosis (ALS), also includes patients with progressive MS, reflecting the drug’s potential across neurodegenerative diseases. This trial is a double-blind, placebo-controlled study with a 12-month treatment phase followed by a 6-month open-label extension, assessing functional outcomes and survival measures.
In addition to pharmacological treatments, clinical trials are exploring **cellular therapies** such as P-CD19CD20-ALLO1, an allogeneic CAR T-cell therapy targeting B cells implicated in MS. This study is designed to evaluate safety, tolerability, and pharmacodynamics in both progressive and relapsing MS populations. Although not yet recruiting, this approach represents a cutting-edge immunotherapy strategy aiming to reset the immune system and halt disease progression.
Non-drug interventions are also being tested. For example, exercise feasibility trials are underway to assess the impact of structured physical activity on disease outcomes in youth with MS, including progressive forms. These trials evaluate physical activity levels, cognitive function, and psychosocial outcomes, recognizing the importance of lifestyle factors in managing MS symptoms and progression.
Other ongoing studies include trials of **N-acetyl cysteine (NAC)**, an antioxidant, to evaluate its effectiveness in progressive MS, and investigations into the use of **ocrelizumab**, a B-cell depleting monoclonal antibody already approved for PPMS, to further understand its long-term safety and effectiveness in broader progressive MS populations.
In summary, the latest clinical trials for progressive MS encompass a range of strategies from novel oral immunomodulators like vidofludimus calcium and ibudilast, to advanced cellular therapies and supportive lifestyle interventions. These studies reflect a growing understanding of the complex mechanisms driving progressive MS and a commitment to developing treatments that can slow or halt its relentless course.
