In the phase III randomized, double-blind, double-dummy, active-controlled, multicenter ASCLEPIOS I and II trials «Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab v...»1, with a typical relapsing MS populations (mean age 38 years, female sex 68%) and with a relatively high proportion of patients being previously exposed to one or more disease modifying therapies, participants were randomized to receive ofatumumab (n = 946) or teriflunomide 14mg (n = 936) for up to 30 months. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09 ). In ASCLEPIOS I, the mean number of gadolinium-enhancing lesions per T1-weighted MRI scan was 0.01 with ofatumumab and 0.45 with teriflunomide (97% lower number of lesions with ofatumumab, P<0.001); in ASCLEPIOS II, the corresponding numbers were 0.03 and 0.51, respectively (94% lower with ofatumumab, P<0.001). In ASCLEPIOS I, the mean number of new or enlarging lesions per year on T2-weighted MRI was 0.72 with ofatumumab and 4.00 with teriflunomide (82% lower number of lesions with ofatumumab, P<0.001); corresponding values in ASCLEPIOS II were 0.64 and 4.15, respectively (85% lower with ofatumumab, P<0.001). In ASCLEPIOS I, the serum neurofilament light chain concentration was lower in the ofatumumab group than in the teriflunomide group by 7% at month 3 (P=0.01), by 27% at month 12, and by 23% at month 24. Corresponding differences in ASCLEPIOS II were 11% (P<0.001), 26%, and 24%. The percentage of patients who reported a serious infection was 2.5% with ofatumumab and 1.8% with teriflunomide.
In the phase II, multicenter, randomized, double-blind, placebo-controlled MIRROR study «Bar-Or A, Grove RA, Austin DJ, ym. Subcutaneous of...»2 with a typical relapsing Multiple Sclerosis populations (mean age 37 years, female sex 67%), 231 patients received either placebo or ofatumumab every 12 weeks or every 4 weeks. The 12-week placebo-controlled period was considered sufficient to estimate efficacy and at week 12, all patients in the placebo group received a single ofatumumab dose. In post hoc analysis, the reduction in the mean rate of cumulative new gadolinium-enhancing lesions from weeks 4 to 12 ranged from 71% (0.29 [95% CI 0.133–0.643]) to 92% (0.08 [95% CI 0.044–0.162]) across ofatumumab groups vs placebo (p ≤0.002). Over the 24-week treatment period, 17 (25%) patients relapsed in the placebo group vs 3 to 10 patients (9%–22%) across the ofatumumab groups. Overall rates of any infection-related AEs were similar across treatment groups.
APOLITOS study «Kira JI, Nakahara J, Sazonov DV, ym. Effect of ofa...»3 included a 24-week, double-blind, placebo-controlled core-part. Sixty-four patients aged 18–55 years, with the mean age of 35.2 years, were randomized (ofatumumab, n = 43; placebo, n = 21). Ofatumumab reduced gadolinium-enhancing lesions per scan versus placebo by 93.6% (adjusted mean of 0.067 vs 1.041, p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized new T2 lesion rate versus placebo by week 24 (adjusted annualized mean rate: 3.734 vs 13.153), with a relative reduction of 71.6% (p = 0.002). The annulized relapse rate was lower in the ofatumumab than in the placebo group (0.264 vs 0.629) with 58.0% rate reduction (p = 0.119). Neither serious nor opportunistic infections were reported.