Approval Status: Approved March 2017
Specific Treatments: multiple sclerosis
Ocrevus (ocrelizumab) is a CD20-directed cytolytic antibody.
Ocrevus is specifically indicated for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis.
Ocrevus is supplied as a solution for intravenous administration. Hepatitis B virus screening is required before the first dose. Pre-medicate 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 6 months. Ocrevus must be diluted prior to administration. Patients should be monitored closely during and for at least one hour after infusion.
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 2 weeks apart, and subsequent doses were administered as a single 600 mg IV infusion) and placebo subcutaneous injections were given 3 times per week. The dose of REBIF, the active comparator, was 44 mcg given as subcutaneous injections 3 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% of Ocrevus-treated and 17% 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% of Ocrevus-treated and 23% 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 endpoint: 46% (p<0.0001) (Study 1) and 47% (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% Ocrevus versus 15.2% REBIF.
Adverse effects associated with the use of Ocrevus may include, but are not limited to, the following:
- upper respiratory tract infections
- infusion reaction
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.
For additional information regarding Ocrevus or multiple sclerosis, please visit https://www.ocrevus.com/