BARCELONA—The investigational compound amiselimod, which also is known as MT-1303, improves MRI outcomes and reduces annualized relapse rate among patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Results indicate that the drug is well tolerated and may reduce the loss of gray matter volume.
Ludwig Kappos, MD, Chair of Neurology at University Hospital in Basel, Switzerland, and colleagues conducted a phase II proof-of-concept study that compared three doses of amiselimod with placebo. The investigators enrolled 415 patients with relapsing-remitting MS into the study. Participants were randomized to receive placebo or 0.1 mg, 0.2 mg, or 0.4 mg of amiselimod. Each treatment group included approximately 100 people. Patients underwent MRI at baseline and at weeks four, eight, 12, 16, 20, and 24.
Ludwig Kappos, MD
The trial’s primary end point was the number of gadolinium-enhancing lesions from weeks eight to 24. Secondary efficacy end points included the proportion of gadolinium-enhancing-lesion-free patients, the total number of new or enlarged T2 lesions, brain volume, gray matter volume, clinical outcomes, relapse rate, and Expanded Disability Status Scale (EDSS) score.
The study population had active MS and was in a relatively early stage of disease. Patients’ mean EDSS score at baseline ranged between 0.5 and 0.8. The treatment groups were well balanced in terms of demographic, clinical, and imaging variables. The proportion of patients with gadolinium enhancement at baseline, however, varied between 30% and 40% between groups. The group that received the lowest dose of amiselimod had the largest proportion of patients with gadolinium enhancement at baseline. Patients had a median number of two relapses in the previous two years. More than 90% of participants completed the study.
Amiselimod was associated with a dose-dependent reduction in the number of gadolinium-enhancing lesions. Patients who received 0.4 mg of amiselimod had a 77% reduction in gadolinium-enhancing lesions. Participants who received 0.1 mg of amiselimod had an approximately 50% reduction in gadolinium-enhancing lesions. In addition, the two highest doses were associated with a 70% reduction and a 55% reduction, respectively, in the number of new and enlarged T2 lesions.
All three doses of the drug reduced patients’ annualized relapse rate. After 24 weeks of treatment, the 0.4-mg dose of amiselimod reduced the risk of relapse by 0.18. The drug also increased the likelihood of relapse freedom, compared with placebo. The study, however, was not designed to show an effect of treatment on relapses, said Dr. Kappos. Furthermore, amiselimod provided a dose-dependent reduction in gray matter volume loss. The investigators found no difference in disability between treated patients and controls, perhaps because of the study’s short duration, said Dr. Kappos.
The investigators observed no difference in the rate of treatment-emergent adverse events between patients receiving amiselimod and those receiving placebo. Significantly, the researchers did not observe a higher rate of cardiac side effects among treated participants, said Dr. Kappos. Nor was amiselimod associated with a higher rate of infections.
—Erik Greb