On 28 October at the 7th Joint ECTRIMS-ACTRIMS conference held in Paris, MediciNova reported surprisingly good Phase II results for its first-in-class, small-molecule drug ibudilast (MN-166) in progressive types of multiple sclerosis (MS), in which ibudilast produced a 48% reduction in whole-brain atrophy by 96 weeks compared to placebo (p = 0.04).
MediciNova’s ibudilast is under development for the treatment of progressive types of MS. Although ibudilast is an experimental drug and is considered a New Molecular Entity in the US and EU, it has a long history in Asia. Ibudilast is authorized in Japan and Korea in the form of capsules and solution/drops under the brand name Ketas, and has been used to treat complications following stroke and asthma since 1989. MediciNova licensed ibudilast from Kyorin Pharmaceutical as a potential treatment for progressive MS in 2012, with a patent running until 2029.
The Phase IIb clinical trial of ibudilast (SPRINT-MS) involves 255 people with progressive forms of MS. The primary objectives of the study are to evaluate the activity of ibudilast versus placebo at 96 weeks as measured by quantitative magnetic resonance imaging (MRI) analysis for whole brain atrophy.
The topline results announced at the conference are a surprise to the community, as a previous study of 30mg/day ibudilast in relapsing-remitting MS (RRMS) failed to show any beneficial effect on the rate of newly active lesions or relapses. However, the earlier RRMS trial indicated possible neuroprotection properties for ibudilast, and prompted MediciNova to further examine the efficacy of ibudilast in a Phase IIb trial in progressive MS patients at a much higher dose (100mg/day).
In addition to good efficacy, ibudilast also demonstrated overall good tolerability and safety. The overall retention rate through Week 96 was 86%. The rates of treatment discontinuation for any reason were 30% in the ibudilast group and 25% in the placebo group, and the rates of discontinuation due to an adverse event (AE) were 18% and 12%. There were no significant differences between the ibudilast group and the placebo group. However, the incidence of AEs is slightly higher in the ibudilast group compared to the placebo group (any AE, 67% in the ibudilast group vs. 48% in the placebo group, p = 0.002).
The Phase IIb efficacy result for ibudilast on reduction in brain atrophy is surprising but promising. However, as a neuroprotection agent, ibudilast is unlikely to produce a beneficial effect for patients in whom brain atrophy has already occurred. Nevertheless, the magnitude of the 48% reduction in brain atrophy is impressive and it is likely to be significant for the underserved progressive MS patient population currently lacking effective treatment. It would be interesting to see how ibudilast will perform in a larger Phase III trial in the future.
GlobalData (2017). PharmaPoint: Multiple Sclerosis – Global Drug Forecast and Market Analysis to 2026, to be published