The efficacy of BRIUMVI was demonstrated in two randomized, double-blind, double-dummy, parallel group, active comparator-controlled clinical trials of identical design, in patients with RMS treated for 96 weeks [Study 1 (NCT03277261) and Study 2 (NCT03277248)]. Patients were randomized to receive either BRIUMVI, given as an IV infusion of 150 mg for the first infusion, 450 mg two weeks after the first infusion for the second infusion/second dose, and 450 mg every 24 weeks after the first infusion for subsequent doses (third infusion and beyond) with oral placebo administered daily; or teriflunomide, the active comparator, given orally as a 14 mg daily dose with IV placebo administered on the same schedule as BRIUMVI. Both studies enrolled patients who had experienced at least one relapse in the previous year, two relapses in the previous two years, or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year. Patients were also required to have an Expanded Disability Status Scale (EDSS) score from 0 to 5.5 at baseline. Neurological evaluations were performed at baseline, every 12 weeks, and at the time of a suspected relapse. Brain MRI scans were performed at baseline and at Weeks 12, 24, 48, and 96.

The primary outcome of both Study 1 and Study 2 was the annualized relapse rate (ARR) over the treatment period. Additional outcome measures included: the total number of MRI T1 Gd- enhancing lesions by Week 96, the total number of new or enlarging MRI T2 hyperintense lesions by Week 96, and time to confirmed disability progression for at least 12 weeks. Disability progression was defined as an increase of greater than or equal to 1.0 point from the baseline EDSS score that was attributable to MS when the baseline score was 5.5 or less, and greater than or equal to 0.5 points when the baseline score was above 5.5. Confirmed disability progression was evaluated in a pooled analysis of Studies 1 and 2. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit 12 weeks after the initial documentation of neurological worsening.

In Study 1, 274 patients were randomized to BRIUMVI and 275 to teriflunomide. Of those randomized to BRIUMVI, 88% completed the 96-week treatment period; of those randomized to teriflunomide, 92% completed the 96-week treatment period. The baseline demographic and disease characteristics were balanced between the two treatment groups. At baseline, the mean age was 37 years, 97% were White, and 63% were female.

In Study 2, 272 patients were randomized to BRIUMVI and 273 to teriflunomide. Of those randomized to BRIUMVI, 93% completed the 96-week treatment period; of those randomized to teriflunomide, 88% completed the 96-week treatment period. The baseline demographic and disease characteristics were balanced between the two treatment groups. At baseline, the mean age was 35 years, 99% were White, and 65% were female.

In Study 1 and Study 2, BRIUMVI significantly lowered the ARR compared to teriflunomide. BRIUMVI statistically significantly reduced the number of T1 Gd-enhancing lesions and the number of new or enlarging T2 lesions in both studies compared to teriflunomide. There was no statistically significant difference in disability progression confirmed at 12 weeks between BRIUMVI-treated and teriflunomide-treated patients.

Results for Study 1 and Study 2 are presented in Table 3.

In exploratory analyses of Study 1 and Study 2, a similar effect of BRIUMVI on the ARR was observed in subgroups defined by gender, prior non-steroid MS therapy, baseline disability (EDSS 3.5 or lower versus greater than 3.5), the number of relapses in the 2 years prior to study enrollment, and number of Gd-enhancing lesions at baseline.