An exploratory analysis of 12- and 24-week composite confirmed disability progression in patients with primary progressive multiple sclerosis in the ORATORIO trial
Author(s): ,
G Giovannoni
Affiliations:
Queen Mary University of London, London, United Kingdom
,
D.L Arnold
Affiliations:
McGill University;NeuroRx Research, Montreal, QC, Canada
,
A Bar-Or
Affiliations:
McGill University
,
J De Sèze
Affiliations:
University Hospital of Strasbourg, Strasbourg, France
,
B Hemmer
Affiliations:
Technische Universität München;Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
,
X Montalban
Affiliations:
Hospital Vall d'Hebron University, Barcelona, Spain
,
K.W Rammohan
Affiliations:
University of Miami, Miami, FL, United States
,
S Belachew
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
C Bernasconi
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
P Chin
Affiliations:
Queen Mary University of London, London, United Kingdom0
,
H Garren
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
D Masterman
Affiliations:
Queen Mary University of London, London, United Kingdom0
,
A Sauter
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
W Wei
Affiliations:
F. Hoffmann-La Roche Ltd., Basel, Switzerland
,
J Wolinsky
Affiliations:
Queen Mary University of London, London, United KingdomQueen Mary University of London, London, United Kingdom
on behalf of the ORATORIO Clinical Investigators
on behalf of the ORATORIO Clinical Investigators
Affiliations:
ECTRIMS Online Library. Giovannoni G. Sep 15, 2016; 146586; P746
Gavin Giovannoni
Gavin Giovannoni
Contributions
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Abstract

Abstract: P746

Type: Poster

Abstract Category: Therapy - disease modifying - Treatment of progressive MS

Background: Data from Phase III trials suggest that selective B-cell targeting may be a potential therapeutic approach in relapsing and primary progressive multiple sclerosis (PPMS). Ocrelizumab (OCR), a humanised monoclonal antibody that selectively targets CD20+ B cells, has shown superior efficacy compared with placebo (PBO) in the Phase III ORATORIO study in patients with PPMS, in which the primary endpoint was 12-week confirmed disability progression (CDP). To address limitations in using the Expanded Disability Status Scale to define clinical disability progression, a composite measure of CDP (cCDP), which also includes measures of upper extremity function and ambulation speed, was used to assess the effect of OCR in patients with PPMS.

Objective: To assess the effect of OCR on 12- and 24-week cCDP in patients with PPMS.

Methods: Patients were randomised (2:1) to receive OCR 600mg as two 300mg intravenous infusions 14 days apart or matching PBO every 24 weeks for ≥120 weeks until an overall prespecified number of CDP events occurred. cCDP was defined as time to first onset of either CDP, ≥20% worsening on the timed 25-foot walk (T25FW) test or ≥20% worsening on the 9-hole peg test (9HPT) sustained for ≥12 or ≥24 weeks. In this exploratory analysis of 12- and 24-week cCDP among the ORATORIO intention-to-treat population, 244 PBO- and 488 OCR-treated patients were evaluable.

Results: Compared with PBO, OCR significantly reduced the risk of 12- and 24-week CDP by 24% (hazard ratio [HR] [95% confidence interval (CI)]: 0.76 [0.59-0.98]; p=0.0321) and 25% (HR [95% CI]: 0.75 [0.58-0.98]; p=0.0365), respectively. OCR vs PBO reduced the risk of 12- and 24-week cCDP by 26% (HR [95% CI]: 0.74 [0.61-0.89]; p=0.0014) and 29% (HR [95% CI]: 0.71 [0.58-0.87]; p=0.0008), respectively. Compared with PBO, OCR also consistently and significantly reduced the risk of 12- and 24-week confirmed ≥20% worsening on T25FW by 25% (HR [95% CI]: 0.75 [0.61-0.92]; p=0.0053) and 27% (HR [95% CI]: 0.73 [0.59-0.91]; p=0.0055), respectively, and the risk of 12- and 24-week confirmed ≥20% worsening on 9HPT by 44% (HR [95% CI]: 0.56 [0.41-0.78]; p=0.0004) and 45% (HR [95% CI]: 0.55 [0.38-0.77]; p=0.0006), respectively.

Conclusions: In ORATORIO, OCR treatment showed consistent benefit on disability progression, ambulation and upper limb function, as demonstrated by significant reduction in the risk of cCDP in patients with PPMS.

Sponsored by F. Hoffmann-La Roche Ltd.

Disclosure:

Gavin Giovannoni
has received honoraria from AbbVie, Bayer HealthCare, Biogen, Canbex Therapeutics, Five Prime Therapeutics, Genzyme, GSK, GW Pharma, Merck, Merck Serono, Novartis, Protein Discovery Laboratories, F. Hoffmann-La Roche Ltd., Synthon, Teva Neuroscience, UCB and Vertex; research grant support from Biogen, Ironwood, Merck Serono, Merz and Novartis; and compensation from Elsevier.

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

Amit Bar-Or has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Genentech, Biogen Idec, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Ono Pharma, Receptos, Sanofi-Genzyme, and Guthy-Jackson/GGF; he has also received research support from Novartis and Sanofi-Genzyme.

Jérôme de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almiral, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd., Genzyme, LFB, Merck, Novartis, and Teva.

Bernhard Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Novartis, Bayer Schering and Genentech; has received speaker honoraria from Biogen Idec and F. Hoffmann-La Roche Ltd.; has received research support from Chugai Pharmaceuticals; holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralising antibodies to interferon-beta.

Xavier Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd., Sanofi, Teva and Trophos.

Kottil W. Rammohan has received honoraria for participating in advisory boards and consulting for Acorda, Biogen, EMD Serono, Genentech, Inc./F. Hoffmann-La Roche Ltd., Genzyme and Teva; he has also received grants from Accera, Novartis and the United States Department of Defense.

Shibeshih Belachew is an employee and shareholder of F. Hoffmann-La Roche Ltd.

Corrado Bernasconi is contractor of F. Hoffmann-La Roche Ltd.

Peter Chin is an employee and/or shareholder of Genentech, Inc.

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

Donna Masterman is an employee and/or shareholder of Genentech, Inc.

Annette Sauter is an employee and shareholder of F. Hoffmann-La Roche Ltd.

Wei Wei is an employee and shareholder of F. Hoffmann-La Roche Ltd.

Jerry Wolinsky has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche Ltd., MedDay Pharmaceuticals, Novartis, Sanofi/Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, F. Hoffmann-La Roche Ltd., Forward Pharma, Genentech, Inc., Novartis, Sanofi/Genzyme, Takeda, Teva, and XenoPort; research support from Sanofi/Genzyme, the United States National Institutes of Health and the US National Multiple Sclerosis Society through The University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.

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