Randomised Placebo-controlled Phase 3 Study of Delayed-release Dimethyl Fumarate in Patients with Relapsing Multiple Sclerosis from Asia-Pacific and Other Countries

BACKGROUND: The Phase 3 DEFINE/CONFIRM studies demonstrated a favourable benefit-risk profile of delayed-release dimethyl fumarate (DMF), mainly in white MS patients. OBJECTIVE: To report results of a Phase 3 study in MS patients from Asia-Pacific and other countries. METHODS: In this 24-week, randomised, placebo-controlled study, 225 patients from Japan (n=114), South Korea, Taiwan, Czech Republic, and Poland were randomized 1:1 to DMF 240 mg twice daily or placebo. The primary endpoint is the total number of new gadolinium-enhancing (Gd+) lesions over brain MRI scans at Week 12, 16, 20, and 24. Secondary endpoints are the total number of new Gd+ lesions and the number of new/newly enlarging T2 lesions from Baseline to Week 24. RESULTS: A total of 213 patients completed the study. Compared with placebo, DMF reduced the mean number of new Gd+ lesions during Weeks 12–24 by 84% (P<0.0001), mean number of new Gd+ lesions from Baseline to Week 24 by 75% (P<0.0001), and mean number of new/newly enlarging T2 lesions at Week 24 by 63% (P<0.0001). Commonly reported adverse events in DMF-treated patients were flushing and related symptoms (30% [DMF] vs 9% [placebo]) and gastrointestinal tolerability events (33% [DMF] vs 16% [placebo]). Mean absolute lymphocyte counts decreased by ~16% from Baseline to Week 24 in DMF-treated patients, remaining within normal limits. Efficacy and safety in Japanese and Asian subgroups were consistent with the overall population. CONCLUSIONS: These results indicate that the beneficial effects of DMF demonstrated in white patients extend to Asian (including Japanese) MS patients.