Update: On March 28, 2017, Ocrevus (ocrelizumab) was approved by the FDA to or the treatment of primary progressive and relapsing multiple sclerosis. For more information, read this article about the FDA approval.
Ocrelizumab (manufacturer: Roche and Biogen Idec), similar to rituximab, is a humanized monoclonal antibody therapy that targets the protein CD20 on the surface of B-cells (a type of lymphocyte that plays a key role in immune response) and causes select mature B-cells to self-destruct. CD20, the target of ocrelizumab, plays an important role in helping B-cells function in the immune response, so inhibiting CD20 depletes B-cells and limits their proinflammatory function.
How far along is ocrelizumab in the development process?
Three Phase 3 studies of ocrelizumab are currently ongoing or in the recruitment phase and another Phase 2 study has not yet begun recruitment. Two of the Phase 3 studies are being conducted in people with relapsing forms of MS to compare ocrelizumab with Rebif (interferon beta-1a). The third Phase 3 study is being conducted in people with primary-progressive MS (PPMS) and compares ocrelizumab with placebo.
What evidence do we have that ocrelizumab works?
The effectiveness of ocrelizumab in people with relapsing forms of MS was tested in a Phase 2 randomized, placebo-controlled study. The study included 220 people with relapsing-remitting MS (RRMS) and randomly assigned participants to ocrelizumab 600 mg (n=55) or 2000 mg (n=55) (given as 2 infusions separated by 2 weeks), interferon beta-1a (given once weekly) (n=54), or placebo (n=54). The comparative phase of the study lasted 24 weeks, after which all participants were switched to ocrelizumab for another 24 weeks to test effectiveness with a more extended course of treatment. Some participants continued treatment with ocrelizumab up to 96 weeks to test the safety of long-term treatment with the drug. The primary efficacy endpoint (the key measure used to determine the effectiveness of the medication) was the total number of gadolinium (Gd)-enhancing brain lesions as detected by magnetic resonance imaging (MRI).
People who received 600 mg and 2000 mg doses of ocrelizumab had significantly lower total number of Gd-enhancing lesions (89% and 96% lower, respectively), as well as a significantly lower frequency of relapses (80% and 73% lower, respectively) compared with placebo. Both ocrelizumab doses also resulted in significantly lower number of Gd-enhancing lesions compared with interferon beta-1a.
What are the most common adverse effects with ocrelizumab?
In the Phase 2 study, infusion-related adverse effects for the first infusion of ocrelizumab were more common than with placebo. However, by the second infusion, the frequency of infusion-related adverse effects was similar in the ocrelizumab and placebo groups. High-dose ocrelizumab resulted in more serious adverse effects than the lower dose of ocrelizumab. In fact, because of the risk for serious opportunistic infections with ocrelizumab, the drug is no longer being considered for use in rheumatoid arthritis or lupus.