Efficacy and Safety of Ocrelizumab in Relapsing Multiple Sclerosis: Results of the Phase III, Interferon ß-1a-Controlled OPERA I and OPERA II Studies

Thursday, June 2, 2016
Exhibit Hall
Fred Lublin, MD , Icahn School of Medicine at Mount Sinai, New York, NY
Douglas L Arnold, MD , NeuroRx Research, Montreal, QC, Canada
Amit Bar-Or, MD, FRCPC , McGill University, Montreal, QC, Canada
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Stephen L Hauser, MD , University of California, San Franscisco, CA
Krzysztof Selmaj, MD, PhD , Medical University of Lodz, Lodz, Poland
Anthony Traboulsee, MD, FRCPC , University of British Columbia, Vancouver, BC, Canada
Peter Chin, MD , Genentech, Inc., South San Francisco, CA
Paulo Fontoura, MD, PhD , F. Hoffmann-La Roche Ltd., Basel, Switzerland
Hideki Garren, MD, PhD , F. Hoffmann-La Roche Ltd., Basel, Switzerland
Gaelle Klingelschmitt, MSc , F. Hoffmann-La Roche Ltd., Basel, Switzerland
Donna Masterman, MD , Genentech, Inc., South San Francisco, CA
Ludwig Kappos, MD, PhD , University Hospital Basel, Basel, Switzerland
Hans-Peter Hartung, MD, FRCP, FAAN, FANA , Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Ashley J Porter, PhD , Articulate Science, London, United Kingdom of Great Britain and Northern Ireland


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 CD20B 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.