Mechanism of Action

Ocrevus (ocrelizumab) is a CD20-directed cytolytic antibody. The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.

Side Effects

Adverse effects associated with the use of Ocrevus may include, but are not limited to, the following:

Upper respiratory tract infections

Infusion reaction

Dosing/Administration

Ocrevus is supplied as a solution for intravenous administration. Hepatitis B virus screening is required before the first dose. Premedicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion. The recommended starting dose of Ocrevus is a 300-mg intravenous infusion, followed two weeks later by a second 300-mg intravenous infusion. Subsequent doses: 600-mg intravenous infusion every six months. Ocrevus must be diluted prior to administration. Patients should be monitored closely during and for at least one hour after infusion.

Clinical Trial Results

FDA Approval

The FDA approval of Ocrevus was based on two randomized, double-blind, double-dummy, active comparator-controlled clinical trials of identical design in patients with RMS treated for 96 weeks (Study 1 and Study 2). The dose of Ocrevus was 600 mg every 24 weeks (initial treatment was given as two 300-mg IV infusions administered two weeks apart, and subsequent doses were administered as a single 600-mg IV infusion) and placebo subcutaneous injections were given three times per week. The dose of REBIF, the active comparator, was 44 mcg given as subcutaneous injections three times per week and placebo IV infusions were given every 24 weeks. Both studies included patients who had experienced at least one relapse within the prior year, or two relapses within the prior two years, and had an Expanded Disability Status Scale (EDSS) score from 0 to 5.5. The primary outcome of both studies was the annualized relapse rate (ARR). In Study 1, 410 patients were randomized to Ocrevus and 411 to REBIF; 11 percent of Ocrevus-treated and 17 percent of REBIF-treated patients did not complete the 96-week double-blind treatment period. In Study 2, 417 patients were randomized to Ocrevus and 418 to REBIF; 14 percent of Ocrevus-treated and 23 percent of REBIF-treated patients did not complete the 96-week double-blind treatment period. In both studies, Ocrevus significantly lowered the annualized relapse rate and the proportion of patients with disability progression confirmed at 12 weeks after onset compared to REBIF. ARR end point: 46 percent (p<0.0001) (Study 1) and 47 percent (p<0.0001) (Study 2). The primary population for analysis of confirmed disability progression was the pooled population from Studies 1 and 2: 9.8 percent Ocrevus versus 15.2 percent REBIF.