To evaluate the efficacy and safety of ofatumumab in Japanese and Russian relapsing MS (RMS) patients.

Ofatumumab, an FDA-approved anti-CD20 monoclonal antibody, is indicated for the treatment of adults with RMS. APOLITOS was designed to support ofatumumab registration for RMS in Japan. In the 24-week (W) core study, ofatumumab demonstrated superior efficacy to placebo.

Patients completing the randomized (2:1), double-blind, 24W core study entered the open-label extension (data cutoff: W48). Patients initially randomized to placebo switched to ofatumumab (placebo-ofatumumab group) in the extension and those on ofatumumab continued treatment for at least 24 weeks. Outcomes included Gd+ T1 lesions and T2 lesions, relapses, and safety parameters.

Fifty-nine patients (ofatumumab, N=40; placebo-ofatumumab, N=19) entered the extension part; 57 (97%) completed it. In the ofatumumab group, the mean number of Gd+ T1 lesions was low until W24 (0.106) and further abrogated to 0.027 by W48. Similarly, the annualized rate of new/enlarging T2 lesions was 4.810 by W24 and 0.230 by W48. The annualized relapse rate (ARR) of 0.217 at W24 was reduced to 0.081 by W48.

In the placebo-ofatumumab group, the mean number of Gd+ T1 lesions was high until W24 (1.150), with a marked reduction to 0.025 by W48 after switching to ofatumumab. Similarly, the T2 lesion rate dropped from 12.080 to 0.813. ARR was 0.684 until W24 and decreased to 0.083 by W48.

Incidence of treatment-emergent AEs by W48 was 74.6%; injection-related reactions were the most common (ofatumumab, 25.0%; placebo-ofatumumab, 21.1%). These were mild to moderate and predominantly reported with the first dose. No deaths or opportunistic infections were reported.

Continued treatment with ofatumumab was associated with sustained efficacy through 48 weeks and switching to ofatumumab at W24 led to rapid clinical benefit in Japanese and Russian RMS patients. Safety observations were consistent with the Phase 3 ASCLEPIOS I/II trials.