Primary Progressive Multiple Sclerosis (PPMS)
The efficacy and safety of OCREVUS in the treatment of patients with PPMS in a well-balanced, placebo-controlled trial.
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The efficacy of OCREVUS was studied in a randomized, double-blind, placebo-controlled clinical trial in 732 patients with primary progressive multiple sclerosis (PPMS) for at least 120 weeks.
- Baseline demographic and disease characteristics were balanced between the 2 treatment groups
Key clinical and MRI endpoints from ORATORIO
* 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 an increase of 0.5 or more when the baseline score is more than 5.5.
In exploratory subgroup analyses of ORATORIO, the proportion of female patients with disability progression confirmed at 12 weeks after onset was similar in OCREVUS-treated patients and placebo-treated patients (approximately 36% in each group). In male patients, the proportion of patients with disability progression confirmed at 12 weeks after onset was approximately 30% in OCREVUS-treated patients and 43% in placebo-treated patients. Clinical and MRI endpoints that generally favored OCREVUS numerically in the overall population, and that showed similar trends in both male and female patients, included annualized relapse rate, change in T2 lesion volume, and number of new or enlarging T2 lesions.
TIME TO ONSET OF CONFIRMED DISABILITY PROGRESSION SUSTAINED FOR AT LEAST 12 WEEKS†
† With the initial event of neurological worsening occurring during the double-blind treatment period in ORATORIO. All patients in this analysis had a minimum of 120 weeks of follow-up. The primary analysis is based on all events accrued including 21 without confirmatory EDSS at 12 weeks.
PROPORTION OF PATIENTS WITH 20 PERCENT WORSENING OF THE TIMED 25-FOOT WALK CONFIRMED AT 12 WEEKS
- In the overall population in ORATORIO, the proportion of patients with 20 percent worsening of the timed 25-foot walk confirmed at 12 weeks was 49% in OCREVUS-treated patients compared to 59% in placebo-treated patients (25% risk reduction)
Adverse reactions associated with OCREVUS in ORATORIO
In a placebo-controlled clinical trial (ORATORIO), a total of 486 patients with PPMS received one dose of OCREVUS (600 mg of OCREVUS administered as two 300 mg infusions 2 weeks apart) given intravenously every 24 weeks, and 239 patients received placebo intravenously. The overall exposure in the controlled treatment period was 1416 patient-years, with median treatment duration of 3 years. The most common adverse reactions in the PPMS trial (incidence ≥10%) were upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections.
‡ One dose of OCREVUS (600 mg administered as two 300 mg infusions 2 weeks apart).
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.
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.