For MS Patients in Japan, Kesimpta May Be Best at Preventing Relapses

Kesimpta (ofatumumab) may be more effective at reducing relapse rates than other disease-modifying therapies (DMTs) in Japanese adults with relapsing forms of multiple sclerosis (MS), according to a review of clinical trial data.

Although the differences were not statistically significant, the study provided comparative evidence that may help inform treatment decisions among patients with relapsing MS in Japan, the researchers noted.

The review study, “A systematic review and network meta-analysis comparing ofatumumab with other disease-modifying therapies available in Japan for the treatment of patients with relapsing multiple sclerosis,” was published in the journal Clinical & Experimental Neuroimmunology.

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Approved for relapsing forms of MS, Kesimpta is an antibody that can lower relapses and slow disability progression by blocking the activity of immune B-cells. These cells are known to participate in the abnormal immune attacks that drive MS.

“Comparisons of efficacy with different DMTs are needed to inform treatment decisions for patients with MS  in Japan,” the researchers wrote.

However, there have been no head-to-head studies in Japan evaluating Kesimpta — the first B-cell-targeting therapy approved for MS in the country — against other MS treatments. Recent meta-analyses of published data from clinical trials also have not considered studies conducted in Japan.

To address this, researchers at Eversana and Novartis, which markets Kesimpta, reviewed published studies up to June 2020 that reported results from randomized and controlled trials testing Kesimpta and other Japan-approved DMTs in relapsing MS patients. Only trials in which at least half of the population was Japanese were eligible.

From the initial 212 hits, four multicenter, 24-week trials — covering 554 adult patients, 411 of whom were Japanese — were included in the meta-analysis.

The APOLITOS Phase 2 trial (NCT03249714), whose results supported Kesimpta’s approval in Japan, tested Kesimpta against a placebo in Japanese and Caucasian patients (from Russia).

The APEX Phase 3 study (NCT01838668) compared the efficacy of Tecfidera (dimethyl fumarate) to a placebo in patients from East Asian countries (Japan, South Korea, and Taiwan) and European countries (Poland and the Czech Republic).

The other two studies were a Phase 2 trial (NCT00537082) that evaluated Gilenya (fingolimod) and a Phase 3 study (NCT01440101) that gauged Tysabri (natalizumab), another antibody-based therapy. Both evaluated the therapy against a placebo in Japanese adults with relapsing MS.

“Although there were some differences in methodology and patient populations, these trials were deemed sufficiently similar to derive reasonable estimates of comparative efficacy,” the scientists wrote.

Researchers initially aimed to compare the treatments’ efficacy across a range of outcomes, including annualized relapse rates (ARR), disability progression, and MRI measures of brain damage, but “only ARR could be used to compare treatments,” they wrote.

A pooled analysis of the four trials revealed that Kesimpta was more effective at reducing ARR than Gilenya (by 16%), Tecfidera (by 39%), or a placebo (by 59%), but not Tysabri, which showed a 33% greater efficacy than Kesimpta. However, these differences failed to reach statistical significance.

Further analysis showed that there was a high probability that Tysabri or Kesimpta was the most effective treatment.

Subgroup analysis including only Japanese patients resulted in similar findings, except for Tysabri. In the Japanese population, Kesimpta was 22% more effective at reducing relapse rates than Tysabri, the team noted. The differences between Kesimpta and a placebo were statistically significant, but not between Kesimpta and the other DMTs.

The small number of patients in each trial, and their clinical differences across the trials, may have influenced the results and prevented the detection of statistically significant differences, the study noted.

These findings, “although limited by the paucity of evidence for Japanese patients, suggest that monoclonal antibody therapies [Kesimpta and Tysabri] may provide improved efficacy in terms of ARR compared with other DMTs available in Japan for the treatment of patients with [relapsing] MS,” the researchers wrote.

They noted, however, that these results represent short-term findings over about five months, which “may not be relevant to longer-term outcomes.”