ACTRIMS 2024
There were a lot of interesting presentations at ACTRIMS Forum this year, including some that are of interest to the general MS community. The major one is the results of the evobrutinib phase III study, the first phase III study of BTK inhibitors in MS to report results. There were 2 simultaneous trials including about 3,000 subjects. Half were on evobrutinib and the other half were treated with teriflunomide (Aubagio). The primary outcome was the annualized relapse rate, and it was no different in the evobrutinib or comparison arms. The secondary outcomes, including disability progression and MRI measures were likewise similar between the groups. This is quite disappointing, since pharma and the MS community have invested an enormous amount of resources in this class of medicines. There are a number of other trials of other BTK inhibitors underway that will report results in the next few years, in both relapsing and progressive MS and the agents differ in selectivity, duration of action, and the amount that gets into the brain. I am hoping that the effects in progressive MS are more promising.
A cautionary result was presented by Dr. Kocot for a group from NIH. They reported that 3 of 9 patients they treated with clemastine worsened in disability. Clemastine is an antihistamine that was found to promote myelin growth in tissue culture in a previous study. It is FDA approved and marketed for treatment of allergies. We have used it off-label in some people with MS based on the initial results and the assumption that it would not cause any worsening. This is a small number of subjects so the results are not definitive. But it is a useful reminder that human biology is complicated and medicines that you think might be helpful could end up being ineffective or even harmful.
As usual at ACTRIMS, there were a number of scientific sessions that I found interesting. There were several talks on remyelination and repair discussing the barriers to remyelination. Convelo Therapeutics has developed methods to test new agents for remyelination and presented results with two candidate drugs in mice and tissue culture. This is a long way from being used in people, but it is an encouraging initial approach. Treatments that repair damaged tissue are badly needed in MS.
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