Ocrelizumab may be closer to approval for the treatment of progressive multiple sclerosis based on the recently published results of two studies. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20-expressing B cells. In the first study, 732 patients with primary progressive multiple sclerosis were randomized 2:1 to receive intravenous ocrelizumab or placebo every 24 weeks for at least 120 weeks and until a pre-specified number of confirmed disability progression events occurred. The percentage of patients with 12-week confirmed disability progression (primary endpoint) was 32.9% with ocrelizumab vs. 39.3% with placebo (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P = 0.03). At 24 weeks, the percentages were 29.6% vs. 35.7%, respectively (HR, 0.75; 95% CI, 0.58-0.98; P = 0.04). At week 120, performance measures had improved with ocrelizumab (25-foot walk test) as well as the total volume of brain lesions on MRI. Side effects with ocrelizumab included infusion-related reactions, URIs, and oral herpes. The rate of neoplasm was 2.3% in the ocrelizumab group vs 0.8% with placebo (N Engl J Med 2017;376:209-220).

The second study compared ocrelizumab to interferon beta-1a in patients presenting with relapsing multiple sclerosis. In two identical studies, 1,656 patients were randomized to ocrelizumab 600 mg intravenously every 24 weeks or subcutaneous interferon beta-1a 44 mcg three times weekly for 96 weeks. The annualized relapse rate was lower with ocrelizumab in both trials (0.16 vs. 0.29; P < 0.001 for both). The percentage of patients with disability progression at 12 and 24 weeks was better with ocrelizumab, as were MRI findings. Serious infections were lower with ocrelizumab compared to interferon, while neoplasms occurred in 0.5% patients treated with ocrelizumab vs. 0.2% of those treated with interferon beta-1a. Both the placebo-controlled trial and the head-to-head study confirm the efficacy of ocrelizumab. However, further safety studies are required, especially regarding the rate of neoplasm (N Engl J Med 2017;376:221-234). The FDA has granted the manufacturer of ocrelizumab Breakthrough Therapy designation, which allows for an expedited review process.