Ibudilast, labeled MN-166 by MediciNova, is a potential oral treatment for all forms of multiple sclerosis (MS) and for other neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). The drug, currently in clinical testing for these diseases, has been marketed in Japan and Korea to treat post-stroke complications and bronchial asthma for over two decades.
MediciNova licensed the drug from Kyorin Pharmaceutical for its potential use in relapsing-remitting multiple sclerosis (RRMS), and later obtained rights to investigate it in progressive MS and other neurological conditions.
In 2016, the drug received Fast Track designation from the U.S. Food and Drug Administration (FDA) to help speed its development as an MS treatment.
How ibudilast works
MS is an autoimmune disease, the symptoms of which are caused by aberrant activation of the immune system. The body attacks myelin sheath, the protective layer that insulates nerve fibers, causing inflammation. This results in disrupted nerve signals and potentially permanent nerve damage.
Inflammation is regulated by proteins called cytokines that are secreted by immune cells.
Ibudilast is a small molecule that acts to suppress three cytokines that promote inflammation: IL-1ß, TNF-a, and IL-6. By blocking these cytokines, it aims to reduce the inflammatory response. Ibudilast may also upregulate the anti-inflammatory cytokine IL-10, and has been shown to be a toll-like receptor 4 (TLR4) functional antagonist — a substance that produces an effect that opposes the normal response. TLR4 is involved in pro-inflammatory signaling pathways, and blocking this may contribute to ibudilast’s ability to reduce neuroinflammation.
Ibudilast in clinical trials
MediciNova completed a Phase 2 multicenter, randomized, and placebo-controlled clinical trial of ibudilast in 297 patients with relapsing MS in April 2008. The results, presented at the World Congress for Treatment and Research in MS (WCTRIMS) that same year, were promising. Ibudilast demonstrated significant positive outcomes in three measures indicative of a potential disease-modifying effect — slower rates of disability due to nerve fiber damage, reduced brain volume loss, and a lower relative risk of new inflammatory lesions converting to persistent black holes, which are associated with relapses. The treatment was also well-tolerated over the trial’s two years.
In 2013, MediciNova announced the initiation of a Phase 2b clinical trial (NCT01982942), called SPRINT-MS, in 250 patients with primary and secondary progressive forms of MS. This trial aims to determine the safety, tolerability, and activity of ibudilast, administered twice daily at a 100 mg per day dose, compared to a placebo over 96 weeks. It is funded by the National Institutes of Health (NIH) and is being conducted by NeuroNEXT, part of the National Institute of Neurological Disorders and Stroke (NINDS). Data from this trial, expected expected to conclude in May 2017, is awaited.
MediciNova was awarded a method of use patent in January 2012, which runs until 2029, to treat patients with both primary progressive MS (PPMS) and secondary progressive MS (SPMS) with ibudilast, either alone or in combination with other drugs.
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