Investigational therapy ibudilast leads to a significant reduction of brain atrophy, supporting its potential to effectively treat progressive multiple sclerosis (MS), new data from a Phase 2 clinical trial show.
These results will be shared at the upcoming 2018 Annual Meeting of the American Academy of Neurology, taking place April 21-27 in Los Angeles, in a presentation titled “A Phase II Trial of Ibudilast in Progressive Multiple Sclerosis.”
Ibudilast (previously known as MN-166), an oral therapy being developed by MediciNova, works by suppressing three cytokines that promote inflammation: IL-1ß, TNF-a, and IL-6. The therapy has been suggested to have a neuroprotective effect on relapsing-remitting MS.
In the Phase 2 SPRINT-MS trial (NCT01982942), researchers assessed the effectiveness, safety, and tolerability of ibudilast in progressive MS patients, who have limited therapeutic options.
Conducted at 28 centers across the U.S., the trial randomized 255 patients with primary or secondary progressive MS, with evidence of disability progression in the two years prior enrollment, to treatment with ibudilast or a placebo.
Ibudilast was delivered in daily doses up to 100 mg for 96 weeks (1.8 years). Clinical and imaging outcomes were assessed every 24 weeks (5.5 months).
The study’s primary objective was to evaluate changes in brain atrophy over the treatment period, using an analysis process called brain parenchymal fraction.
The final analysis included 244 patients, of whom 220 (86 percent) completed the 96 weeks of treatment.
Results showed that treatment with ibudilast was associated with a significant reduction in the rate of brain atrophy progression — by 48 percent — as measured by the brain parenchymal fraction.
Additionally, the team detected no increase in the rate of serious adverse effects or discontinuation rates between the two groups.
“The adverse events reported more commonly with ibudilast included gastrointestinal (nausea, diarrhea, abdominal pain, and vomiting), rash, depression, and fatigue,” the researchers wrote.
Other endpoints included magnetization transfer ratio and diffusion tensor imaging, among others. Both are used to evaluate the degree of disease changes associated with MS.
Results showed that ibudilast led to a significant reduction in magnetization transfer ratio change, between 77% and 82%, and a trend for improvement on transverse diffusivity, although the improvements didn’t reach statistical significance.
“Ibudilast met its primary outcome of brain atrophy. Safety and tolerability were also favorable. These results support further investigation of ibudilast as a potential treatment for progressive MS,” the team concluded.