Ibudilast (MN-166)

Ibudilast, labeled MN-166 by MediciNova, is a potential oral treatment for all forms of multiple sclerosis (MS), as well as for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS).

While ibudilast is currently in clinical testing for MS, it has been marketed in Japan and Korea for more than two decades as a treatment for post-stroke complications and bronchial asthma. According to MediciNova, more than 3.2 million people have been prescribed the medication, and it has shown a good safety profile in real-world use for those indications.

MediciNova licensed ibudilast 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. The U.S. Food and Drug Administration (FDA) put ibudilast on its fast track program as a potential MS treatment in 2016. 

How ibudilast works

MS is caused by the immune system erroneously launching an inflammatory attack against healthy cells in the brain and spinal cord. Ibudilast is a small molecule that is believed to modulate the activity of certain cytokines —  signaling molecules that coordinate the activity of the immune system.

Specifically, ibudilast blocks the activity of three pro-inflammatory cytokines, called interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-a), and interleukin-6 (IL-6). Simultaneously, it is thought to increase the activity of an anti-inflammatory cytokine called interleukin-10 (IL-10).

The investigational small molecule also has been shown to be a toll-like receptor 4 (TLR4) functional antagonist. TLR4 is a receptor protein on the surface of cells that, when activated, triggers a pro-inflammatory response. Being a “functional antagonist” means that ibudilast triggers a biological effect in direct opposition to the normal activity of the receptor, i.e., lessened inflammation. 

Notably, ibudilast is able to cross the blood-brain barrier (BBB). The BBB acts as a barrier that regulates which substances in the blood are able to get into the brain. Crossing the BBB has been a major challenge in the creation of medications that aim to target the brain.

Ibudilast in clinical trials

MediciNova completed a randomized, placebo-controlled Phase 2 clinical trial of ibudilast in people with relapsing MS in April 2008. The trial enrolled 297 participants, who were assigned randomly to one of two doses (30 or 60 mg) of the medication, or a placebo, taken daily.

Results showed the treatment significantly reduced the risk of disability progression, slowed brain volume loss, and lessened the relative risk of new inflammatory lesions converting to persistent black holes, which are associated with relapses. The treatment also was well-tolerated during the two-year-long trial.

MediciNova launched a Phase 2b clinical trial (NCT01982942) called SPRINT-MS, to test ibudilast in people with progressive MS in 2013. The trial enrolled 255 people with progressive MS — 134 with primary progressive MS (PPMS) and 121 with secondary progressive MS (SPMS) — who were assigned randomly to receive either a placebo or ibudilast, at doses up to 100 mg, for 96 weeks (almost two years).

Results showed that ibudilast significantly slowed the rate of brain atrophy, by 48%. An additional analysis conducted after the trial showed that this effect was driven mainly by the therapy’s impact in people with PPMS, likely because atrophy progressed more quickly in the absence of treatment for individuals with that form of the disease. Treatment did not substantially slow brain atrophy for those with SPMS.

MediciNova is planning to confirm ibudilast’s benefits in a Phase 3 clinical trial for SPMS patients without relapses. The trial’s main goal is to determine if the treatment reduces the rates of confirmed disability progression.

In 2019, MediciNova announced plans to launch a Phase 3 clinical trial to test ibudilast in people with non-active SPMS — that is, those with SPMS who do not experience disease relapses. Of note, there currently is no approved therapy for this type of MS in the U.S. MediciNova announced it was actively engaging with potential partners that could help fund the study in 2021.

Other information

MediciNova was awarded a patent in January 2012, which is in effect 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.

More recently, the company secured a U.S. patent covering the use of ibudilast to treat eye disease.


Last updated: Sept. 14, 2021


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