The SPRINT-MS trial evaluated the novel drug ibudilast over 96 weeks in patients with primary and secondary progressive multiple sclerosis.
In a conversation at the 2019 in Philadelphia, lead investigator , of the Cleveland Clinic, spoke with 乌鸦传媒 to describe the findings of the study, as well as the differential treatment effects in primary versus secondary progressive MS.
Following is a transcript of his remarks:
The SPRINT-MS trial was a phase II clinical trial of ibudilast, which is an oral therapy being evaluated for progressive MS. It was a two-year trial evaluated in 255 patients recruited from 28 sites across the United States, so it was [a] good-sized phase 2 trial. The primary outcome was a biomarker, whole-brain atrophy, asking the question, "Does ibudilast therapy lead to a slowing in the progression of whole-brain atrophy?" Into the trial, we recruited patients with both primary progressive or secondary progressive MS, and either of those phenotypes were allowed into the trial.
The overall results of the trial was, we found that ibudilast was associated with a 48% slowing in the progression of brain atrophy compared to placebo, which was quite a startling and surprising finding of that magnitude. It was quite a dramatic slowing in the progression of brain atrophy. That then led to the question of, "Was there a similar decline in or slowing in primary progressive and secondary progressive?" Now, those two phenotypes have been considered separate for a long time, and indeed, most clinical trials enroll either primary progressive or secondary progressive MS patients, and typically don't enroll both.
We enrolled both based on a growing sense in the field that there are more similarities between primary and secondary progressive MS than there are differences. There's a growing sense that they're very, very similar in overlapping phenotypes, so we looked at a breakdown. By chance, we enrolled roughly half and half of primary- and secondary progressive MS patients. Again, the trial was open to enrollment of whoever, and just whoever came in is who came in, but it ended up being roughly half and half. That allowed us to have rather good power to look at the differential treatment effects in primary- versus secondary progressive MS.
What we found is that the overall results were driven predominantly by patients with primary progressive MS. There was essentially no slowing of brain atrophy in patients with secondary progressive MS. The benefit was in patients with primary progressive MS. When we looked at what factors might have been driving that, was it because of a difference in baseline brain volume or a difference in T2 lesion volume or age or things like that? We really couldn't find any explanation other than their categorization of primary- versus secondary progressive MS.
One thing we did observe, which pointed towards a potential explanation, is that the rate of atrophy in the placebo groups was over twice as fast in primary progressive MS as secondary progressive MS. That hasn't really been well understood. It was rather surprising that the rate of atrophy was twice as fast, more than twice as fast in the primary progressive patients. It may have been that the secondary progressive patients just didn't have enough atrophy progression to show a potential beneficial effect of a therapeutic intervention, so we may have seen somewhat of [a] floor effect.
We don't know how that relates to a phase 3 trial, of course, in terms of whether there will be a differential clinical benefit in patients with primary- versus secondary progressive MS. For that, we'll just have to wait for the phase III trials.