Efficacy and Safety of Ocrelizumab in Relapsing Multiple Sclerosis: Results of the Phase III, Interferon ß-1a-Controlled OPERA I and OPERA II Studies
B cells are known to contribute to the pathogenesis of multiple sclerosis (MS), which involves early inflammation and concurrent or subsequent neurodegeneration. Ocrelizumab (OCR) is a humanized monoclonal antibody that selectively targets CD20+ B cells.
To evaluate the efficacy and safety of OCR in two identical Phase III, randomized, double-blind, double-dummy trials compared with interferon beta-1a (IFNβ-1a) in relapsing MS (RMS; OPERA I and OPERA II).
Patients were randomized (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFNβ-1a 44 μg three times weekly over the 96-week study period. Eligibility criteria included: age 18-55 years; diagnosis of RMS (2010 revised McDonald criteria); Expanded Disability Status Scale score of 0-5.5; and ≥ 2 documented clinical relapses within 2 years or ≥ 1 within 1 year prior to screening. The primary endpoint was protocol-defined annualized relapse rate (ARR) at 96 weeks. Key secondary endpoints included: time to confirmed disability progression (CDP) sustained for 12 weeks and 24 weeks; total number of T1 Gd-enhancing lesions at weeks 24, 48, and 96; total number of new/enlarging T2 lesions at weeks 24, 48, and 96; and overall safety.
Over the 96-week treatment period and compared with IFNβ-1a, OCR significantly reduced: ARR based on protocol-defined relapses (OPERA I: 46%, p<0.0001; OPERA II: 47%, p<0.0001); ARR based on all clinical relapses (OPERA I: 42%, p=0.0001; OPERA II: 43%, p<0.0001); risk of 12-week and 24-week CDP (prespecified pooled analysis: 12-week CDP, 40% decrease [p=0.0006]; 24-week CDP, 40% decrease [p=0.0025]); total number of T1 Gd-enhancing lesions (OPERA I: 94%, p<0.0001; OPERA II: 95%, p<0.0001); and total number of new/enlarging T2 lesions (OPERA I: 77%, p<0.0001; OPERA II: 83%, p<0.0001). The incidence of adverse events (AEs) and serious AEs were similar across both treatment arms, with the exception of some known AEs associated with OCR (infusion-related reactions and infections) and IFNβ-1a (influenza-like illness and local cutaneous reactions).
OCR was superior to IFNβ-1a in reducing both clinical and brain-imaging measures of disease activity and demonstrated a favorable safety profile in OPERA I and OPERA II, reinforcing the central role of B cells in MS pathophysiology.
Supported by F. Hoffmann-La Roche Ltd.