SUMMARY
- Results were published of a phase 2 clinical trial testing an oral therapy ibudilast (MN-166, MediciNova, Inc.) in people with progressive forms of MS.
- The results demonstrated that ibudilast was well tolerated and significantly slowed the rate of brain atrophy compared to placebo. Brain atrophy (shrinkage) has been linked to cognitive and physical disability in MS.
- The trial was conducted at the Cleveland Clinic and 27 other sites across the U.S., and involved 255 people with primary or secondary progressive MS.
- The study was principally funded by the NIH’s NeuroNEXT Network, a clinical trials initiative of the National Institute of Neurological Disorders and Stroke, with additional support by MediciNova, Inc. and the National MS Society.
- These phase 2 results may lead the way to the testing of ibudilast in larger phase 3 trial(s), which would be needed before the company could apply for marketing approval from the FDA, the European Medicines Agency or other regulatory agencies. Ibudilast was designated by the FDA as a “Fast Track Product” which could speed its future development as a possible treatment of progressive MS.
“These results are a promising step toward a potential new therapy for people living with progressive forms of MS, for whom there are few treatment options. It is gratifying to see our investments in progressive MS starting to pay off.” said Bruce Bebo, PhD, Executive Vice President, Research, National MS Society.
Background: Ibudilast (MN-166, MediciNova, Inc.) inhibits an enzyme called phosphodiesterase, and has been shown to regulate immune pathways that can damage the central nervous system, promote myelin repair, and help protect nerve cells from damage in MS. While considered a “New Molecular Entity” in the United States and Europe, ibudilast is marketed in Asia to treat post-stroke vertigo and asthma. It is also being investigated in the U.S. for its potential to treat ALS and drug addiction. A previous clinical trial of ibudilast in relapsing MS suggested that while it did not prevent new brain lesions, it appeared to slow the progression of brain atrophy (shrinkage).
The current ibudilast trial was principally funded by the NIH’s NeuroNEXT Network, a clinical trials initiative of the National Institute of Neurological Disorders and Stroke, with additional support by MediciNova, Inc., the company that supplied ibudilast. The National MS Society also provided funding support because of the focus on progressive MS and because the trial’s design had potential to answer important questions about the best ways to measure the benefits of therapies aimed at protecting the nervous system from MS.
The Study: The trial, known as “SPRINT-MS,” was led by Robert Fox, MD, Staff Neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic. It was conducted at the Cleveland Clinic and 27 other sites across the U.S. The trial involved 255 participants; about half had primary progressive MS, and the other half had secondary progressive MS. Participants were randomly assigned to be administered oral ibudilast or inactive placebo. About one-third of the participants continued their treatment with an injected disease-modifying therapy (either glatiramer acetate or interferon beta) during the trial.
The primary outcome measure was change in brain atrophy (as measured by an MRI analysis technique called brain parenchymal fraction) after 96 weeks. Brain atrophy has been linked to cognitive and physical disability in MS. Other outcomes measured including additional advanced imaging, safety, clinical and quality of life outcomes.
Results: After 96 weeks, those who were taking ibudilast had a slower rate of brain atrophy compared to those on placebo. The difference was statistically significant, with a 48% reduction in the rate of atrophy in the treated group compared to the placebo group. There were no major safety issues reported. The most common side effects experienced by those taking ibudilast were gastrointestinal problems (such as nausea, diarrhea, abdominal pain and vomiting) and depression.
Results were
published in the August 30, 2018 issue of
The New England Journal of Medicine. Preliminary results had been previously presented at medical meetings.
What’s Next? These phase 2 results may lead the way to the testing of ibudilast in larger phase 3 trial(s), which would be needed before the company could apply for marketing approval from the FDA, the European Medicines Agency or other regulatory agencies. Ibudilast was
designated by the U.S. Food and Drug Administration as a “Fast Track Product” which could speed its future development as a possible treatment of progressive MS.