Efficacy and safety of ocrelizumab in relapsing multiple sclerosis - results of the interferon-beta-1a-controlled, double-blind, Phase III OPERA I and II studies
Author(s): ,
S.L. Hauser
Affiliations:
University of California, San Francisco, CA, United States
,
G.C. Comi
Affiliations:
University Vita-Salute San Raffaele, Milan, Italy
,
H.-P. Hartung
Affiliations:
Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
,
K. Selmaj
Affiliations:
Medical University of Lodz, Lodz, Poland
,
A. Traboulsee
Affiliations:
The University of British Columbia, Vancouver, BC
,
A. Bar-Or
Affiliations:
McGill University
,
D.L. Arnold
Affiliations:
McGill University; NeuroRx Research, Montreal, QC, Canada
,
G. Klingelschmitt
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
A. Kakarieka
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
F. Lublin
Affiliations:
Icahn School of Medicine at Mount Sinai, New York, NY, United States
,
H. Garren
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
L. Kappos
Affiliations:
University Hospital Basel, Basel, Switzerland
on behalf of the OPERA I and II clinical investigators
on behalf of the OPERA I and II clinical investigators
Affiliations:
ECTRIMS Online Library. Hauser S. 10/09/15; 116634; 246
Stephen Hauser
Stephen Hauser
Contributions
Abstract
Abstract: 190

Type: Oral

Abstract Category: Immunomodulation / Immunosuppression

Background: B cells are believed to contribute to the pathogenesis of multiple sclerosis (MS). Ocrelizumab (OCR) is a recombinant humanised monoclonal antibody that selectively targets CD20+ B cells.

Objectives:
OPERA I and II are two identical Phase III, multicentre, randomised, double-blind, double-dummy, parallel-group trials aiming to assess the efficacy and safety of OCR compared with interferon (IFN)-β-1a in patients with relapsing forms of MS (RMS; OPERA I/NCT01247324 and OPERA II/NCT01412333).

Methods:
Patients were randomised (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or IFN-β-1a 44 µg subcutaneously three times per week throughout a 96-week treatment period. Eligibility criteria included an age of 18-55 years with a diagnosis of RMS (2010 revised McDonald criteria), Expanded Disability Status Scale (EDSS) score of 0-5.5 at screening and ≥ two documented clinical attacks within 2 years prior or one within 1 year prior to screening. The primary endpoint is the annualised protocol-defined relapse rate at 2 years.

Results:
OPERA I and II randomised 821 and 835 patients, respectively. Mean (standard deviation, SD) age at baseline was 37.0 (9.3) years in OPERA I and 37.3 (9.0) years in OPERA II; 66% of patients in both studies were female. Mean (SD) baseline EDSS scores were 2.77 (1.26)/2.75 (1.34); mean (SD) duration since MS symptom onset was 6.48 (6.16)/6.70 (6.11) years; and mean (SD) duration since MS diagnosis was 3.77 (4.72)/4.14 (5.01) years, for OPERA I/II, respectively. Mean (SD) number of relapses in the 1 and 2 years prior to randomisation was 1.32 (0.65)/1.33 (0.71) and 1.77 (0.89)/1.78 (0.94), respectively, in OPERA I/II. The number of patients untreated with any MS medication in the prior 2 years was 595 (72.5%) for OPERA I and 616 (73.8%) for OPERA II. At baseline, 40.3% and 40.2% of patients had gadolinium-enhancing (Gd+) T1 lesions; mean (SD) number of Gd+ T1 lesions was 1.78 (4.69) and 1.87 (4.88); median (min-max) volume of T2 lesions was 5.88 (0.0-83.2) cm3 and 5.65 (0.0-96.0) cm3; and mean (SD) normalised brain volume was 1500.06 (85.86) cm3 and 1502.72 (91.55) cm3 on brain magnetic resonance imaging in OPERA I and II, respectively.

Conclusions: These baseline data indicate that the populations enrolled in the OPERA I and II studies are consistent with an RMS population. The results of the OPERA studies will provide information on the efficacy and safety of OCR compared with IFN-β-1a in patients with RMS.

Disclosure: Research funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Stephen L Hauser has received grant/research support from F. Hoffmann-La Roche Ltd., Symbiotix and Bionure (SAB member).

Giancarlo C Comi has received compensation for consulting services and/or speaking activities from F. Hoffmann-La Roche Ltd., Novartis, Teva, Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Serono Symposia International Foundation, Excemed, Almirall, Chugai and Receptos.

Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine University from Bayer, Biogen, F. Hoffmann-La Roche Ltd., GeNeuro, Genzyme, Merck Serono, MedImmmune, Novartis, Octapharma, Opexa, Teva and Sanofi Aventis.

Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, Genzyme.

Anthony Traboulsee has received grant support from F. Hoffmann-La Roche Ltd. and Sanofi Genzyme; is a steering committee member for F. Hoffmann-La Roche Ltd.; and has been a consultant for Biogen, Chugai, EMD Serono, F. Hoffmann-La Roche Ltd., Medimmune, Sanofi Genzyme, Teva Neuroscience.

Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from: Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, F. Hoffmann-La Roche Ltd., Genentech, GSK, Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, Sanofi-Aventis, Teva Neuroscience and Wyeth.

Douglas Arnold reports equity interest in NeuroRx Research, which performed the MRI analysis for the trial, and consultation fees from Acorda, Biogen Idec, Genzyne, F. Hoffmann-La Roche Ltd., Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi Aventis, and Teva.

Gaelle Klingelschmitt is an employee of F. Hoffmann-La Roche Ltd.

Algirdas Kakarieka is an employee of F. Hoffmann-La Roche Ltd.

Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis,Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd., Genentech, Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies, Akros; is co-Chief Editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.

Hideki Garren is an employee of F. Hoffmann-La Roche Ltd.

Ludwig Kappos's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).

Abstract: 190

Type: Oral

Abstract Category: Immunomodulation / Immunosuppression

Background: B cells are believed to contribute to the pathogenesis of multiple sclerosis (MS). Ocrelizumab (OCR) is a recombinant humanised monoclonal antibody that selectively targets CD20+ B cells.

Objectives:
OPERA I and II are two identical Phase III, multicentre, randomised, double-blind, double-dummy, parallel-group trials aiming to assess the efficacy and safety of OCR compared with interferon (IFN)-β-1a in patients with relapsing forms of MS (RMS; OPERA I/NCT01247324 and OPERA II/NCT01412333).

Methods:
Patients were randomised (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or IFN-β-1a 44 µg subcutaneously three times per week throughout a 96-week treatment period. Eligibility criteria included an age of 18-55 years with a diagnosis of RMS (2010 revised McDonald criteria), Expanded Disability Status Scale (EDSS) score of 0-5.5 at screening and ≥ two documented clinical attacks within 2 years prior or one within 1 year prior to screening. The primary endpoint is the annualised protocol-defined relapse rate at 2 years.

Results:
OPERA I and II randomised 821 and 835 patients, respectively. Mean (standard deviation, SD) age at baseline was 37.0 (9.3) years in OPERA I and 37.3 (9.0) years in OPERA II; 66% of patients in both studies were female. Mean (SD) baseline EDSS scores were 2.77 (1.26)/2.75 (1.34); mean (SD) duration since MS symptom onset was 6.48 (6.16)/6.70 (6.11) years; and mean (SD) duration since MS diagnosis was 3.77 (4.72)/4.14 (5.01) years, for OPERA I/II, respectively. Mean (SD) number of relapses in the 1 and 2 years prior to randomisation was 1.32 (0.65)/1.33 (0.71) and 1.77 (0.89)/1.78 (0.94), respectively, in OPERA I/II. The number of patients untreated with any MS medication in the prior 2 years was 595 (72.5%) for OPERA I and 616 (73.8%) for OPERA II. At baseline, 40.3% and 40.2% of patients had gadolinium-enhancing (Gd+) T1 lesions; mean (SD) number of Gd+ T1 lesions was 1.78 (4.69) and 1.87 (4.88); median (min-max) volume of T2 lesions was 5.88 (0.0-83.2) cm3 and 5.65 (0.0-96.0) cm3; and mean (SD) normalised brain volume was 1500.06 (85.86) cm3 and 1502.72 (91.55) cm3 on brain magnetic resonance imaging in OPERA I and II, respectively.

Conclusions: These baseline data indicate that the populations enrolled in the OPERA I and II studies are consistent with an RMS population. The results of the OPERA studies will provide information on the efficacy and safety of OCR compared with IFN-β-1a in patients with RMS.

Disclosure: Research funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Stephen L Hauser has received grant/research support from F. Hoffmann-La Roche Ltd., Symbiotix and Bionure (SAB member).

Giancarlo C Comi has received compensation for consulting services and/or speaking activities from F. Hoffmann-La Roche Ltd., Novartis, Teva, Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Serono Symposia International Foundation, Excemed, Almirall, Chugai and Receptos.

Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine University from Bayer, Biogen, F. Hoffmann-La Roche Ltd., GeNeuro, Genzyme, Merck Serono, MedImmmune, Novartis, Octapharma, Opexa, Teva and Sanofi Aventis.

Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, Genzyme.

Anthony Traboulsee has received grant support from F. Hoffmann-La Roche Ltd. and Sanofi Genzyme; is a steering committee member for F. Hoffmann-La Roche Ltd.; and has been a consultant for Biogen, Chugai, EMD Serono, F. Hoffmann-La Roche Ltd., Medimmune, Sanofi Genzyme, Teva Neuroscience.

Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from: Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, F. Hoffmann-La Roche Ltd., Genentech, GSK, Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, Sanofi-Aventis, Teva Neuroscience and Wyeth.

Douglas Arnold reports equity interest in NeuroRx Research, which performed the MRI analysis for the trial, and consultation fees from Acorda, Biogen Idec, Genzyne, F. Hoffmann-La Roche Ltd., Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi Aventis, and Teva.

Gaelle Klingelschmitt is an employee of F. Hoffmann-La Roche Ltd.

Algirdas Kakarieka is an employee of F. Hoffmann-La Roche Ltd.

Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis,Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd., Genentech, Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies, Akros; is co-Chief Editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.

Hideki Garren is an employee of F. Hoffmann-La Roche Ltd.

Ludwig Kappos's institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); royalties (Neurostatus Systems GmbH); grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation).

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