Relapsing Forms of Multiple Sclerosis (RMS)
The efficacy and safety of OCREVUS in the treatment of patients with RMS were evaluated in two identical clinical trials.
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OPERA I and II study designs
OPERA I and II demographics
OPERA I and II endpoints
RMS safety results
Proposed mechanism of action
OPERA I and II study designs in RMS
The efficacy of OCREVUS was compared to Rebif® (interferon β-1a) in 2 randomized, double-blind, double-dummy, active comparator-controlled clinical trials of identical design in a total of 1656 patients with relapsing forms of multiple sclerosis (RMS) treated for 96 weeks.
- Baseline demographic and disease characteristics were balanced between the 2 treatment groups
EDSS=Expanded Disability Status Scale; DMT=disease-modifying therapy; Gd+=gadolinium-enhancing.
OPERA I and II endpoints
Key clinical and MRI endpoints from OPERA I and OPERA II
* Defined as an increase of 1.0 point or more from the baseline EDSS
score for patients with baseline score of 5.5 or less, or 0.5 or more
when the baseline score is greater than 5.5; Kaplan-Meier estimates at
Week 96.
† Data prospectively pooled from OPERA I and
OPERA II.
Note: In exploratory subgroup analyses of OPERA I and
II, the effect of OCREVUS on annualized relapse rate and disability
progression was similar in male and female patients.
TIME TO ONSET OF CONFIRMED DISABILTIY PROGRESSION SUSTAINED FOR AT LEAST 12 WEEKS (SECONDARY ENDPOINT, POOLED)*
*With the initial event of neurological worsening occuring during the double-blind treatment period in OPERA I and II in patients with RMS (pooled ITT population). Prespecified pooled analysis of OPERA I and II.
ITT=intent-to-treat
RMS safety results
Adverse reactions associated with OCREVUS in OPERA I and II
In active-controlled clinical trials (OPERA I and II), 825 patients with RMS received OCREVUS 600 mg intravenously every 24 weeks (initial treatment was given as 2 separate 300 mg infusions at Weeks 0 and 2). The overall exposure in the 96-week controlled treatment periods was 1448 patient-years. The most common adverse reactions in the RMS trials (incidence ≥10%) were upper respiratory tract infections and infusion reactions.
‡ The first dose was given as 2 separate 300 mg infusions at Weeks 0 and 2.
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity.
Patients in MS trials were tested at multiple time points (baseline and every 6 months post-treatment for the duration of the trial) for anti-drug antibodies (ADAs). Out of 1311 patients treated with OCREVUS, 12 (~1%) tested positive for ADAs, of which 2 patients tested positive for neutralizing antibodies. These data are not adequate to assess the impact of ADAs on the safety and efficacy of OCREVUS.
Proposed mechanism of action
OCREVUS is a recombinant humanized monoclonal antibody directed against CD20-expressing B cells. The precise mechanism by which OCREVUS exerts its therapeutic effects in MS 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, OCREVUS results in antibody-dependent cellular cytolysis and complement-mediated lysis.