Definitive results of a phase 2 study published in the New England Journal of Medicine, show that treatment of patients with progressive multiple sclerosis (MS) ibudilast (MN166; MediciNova, La Jolla, CA) had a 48% decrease in the rate of brain-volume loss compared to that seen in patients treated with placebo.
The two-year SPRINT-MS (NCT01982942) study was conducted at 28 sites in the US. Patients were able to enroll if they were taking no medication, interferon-ß, or glatiramer acetate. A total of 255 patients were enrolled in the trial; 129 received 100 mg/day of ibudilast and 126 received placebo. In the treatment arm, 53% had primary-progressive MS (PPMS) and in the placebo arm, 52% of patients had PPMS. All other enrollees had secondary-progressive MS (SPMS). Those in the treatment arm received 100 mg/day for 96 weeks.
Patients treated with ibudilast had a rate of change in brain parenchymal fraction of −0010 annually versus −0.0019 for those treated with interferon-β (P =.04). This difference represents approximately 2.5 mL less brain atrophy with ibudilast over a period of 96 weeks. Adverse events included gastrointestinal symptoms, headache, and depression.
Ibudilast is an anti-inflammatory drug that crosses the blood-brain barrier and inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4.
“These findings are significant for patients with progressive MS,” said Robert Fox, MD, the study’s principal investigator and vice-chair for research in Cleveland Clinic’s Neurological Institute. “Our hope is that the benefit of ibudilast in slowing brain shrinkage will also translate to decreased progression of associated physical disabilities in a future phase 3 trial.”
“There is a significant need for new treatment options to effectively delay disability progression for patients with progressive MS,” said Dr. Fox. “We are hopeful these findings will help us develop more therapies for progressive MS and do so more rapidly and efficiently.”
“Although a larger study is needed to confirm these findings, this promising study brings people with progressive MS, who currently do not have many treatment options, one step closer to a potential therapy,” said Robin Conwit, MD, program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.Next Story