Abstract: Ocrelizumab Efficacy in PPMS Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase III, Placebo-Controlled Trial (2016 CMSC Annual Meeting)

DX06
Ocrelizumab Efficacy in PPMS Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase III, Placebo-Controlled Trial

Friday, June 3, 2016: 3:15 PM

Maryland B

Jerry Wolinsky, MD , University of Texas Health Science Center at Houston, Houston, TX

Douglas L Arnold, MD , McGill University, Montreal, QC, Canada

Amit Bar-Or, MD, FRCPC , McGill University, Montreal, QC, Canada

Jérôme de Seze, MD, PhD , University Hospital of Strasbourg, Strasbourg, France

Gavin Giovannoni, MBBCh, PhD, FCP (Neurol., SA), FRCP, FRCPath , Queen Mary University of London, London, United Kingdom of Great Britain and Northern Ireland

Bernhard Hemmer, MD , Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

Kottil Rammohan, MD , University of Miami, Miami, FL

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

Donna Masterman, MD , Genentech, Inc., South San Francisco, CA

Annette Sauter, MD , F. Hoffmann-La Roche Ltd., Basel, Switzerland

Xavier Montalban, MD, PhD , Hospital Vall d’Hebron University, Barcelona, Spain

Ashley J Porter, PhD , Articulate Science, London, United Kingdom of Great Britain and Northern Ireland

PDF

Background: B cells contribute to multiple sclerosis (MS) pathogenesis, including in primary progressive MS (PPMS) for which there are no approved treatments. Ocrelizumab (OCR) is a humanized monoclonal antibody that selectively targets CD20⁺B cells.

Objectives: To evaluate the efficacy of OCR in patients with PPMS with and without T1 gadolinium-enhancing (Gd⁺) lesions at baseline in a Phase III, randomized, double-blind, placebo-controlled study (ORATORIO).

Methods: A total of 732 patients were randomized (2:1) to receive OCR 600 mg via intravenous (IV) infusions as two 300-mg infusions 14 days apart or placebo (PBO) every 24 weeks for ≥120 weeks until a prespecified number of 12-week confirmed disability progression (CDP) events occurred. Key eligibility criteria included: age 18-55 years, PPMS diagnosis (2005 revised McDonald criteria), and Expanded Disability Status Scale (EDSS) score of 3.0-6.5. The primary endpoint was time to onset of 12-week CDP. Secondary endpoints included time to onset of 24-week CDP and change in total T2 lesion volume from baseline to 120 weeks. Subgroup analyses evaluated these outcomes in patients with and without T1 Gd⁺ lesions at baseline.

Results: Compared with PBO, OCR significantly reduced risk of 12-week CDP by 24% (hazard ratio [HR]=0.76; p=0.0321), 24-week CDP by 25% (HR=0.75; p=0.0365), and T2 lesion volume (−3.4% with OCR vs +7.4% with PBO [p<0.0001]). T1 Gd⁺ lesions were present at baseline in 27.5% of OCR-treated patients vs 24.7% of PBO-treated patients. In patients with and without T1 Gd⁺ lesions at baseline, respectively, OCR reduced the risk of 12-week CDP by 35% (HR=0.65 [95% CI: 0.40–1.06]; p=0.0826) and 16% (HR=0.84 [95% CI: 0.62–1.13]; p=0.2441); the risk of 24-week CDP by 33% (HR=0.67 [95% CI: 0.40–1.14]; p=0.1417) and 19% (HR=0.81 [95% CI: 0.59–1.10]; p=0.1783); and total T2 lesion volume by −3.8% (95% CI: −7.0 to −0.5) with OCR vs 12.0% (95% CI: 7.2–17.1) with PBO (p<0.001) and −3.1% (95% CI: −5.0 to −1.1) with OCR vs 6.1 % (95% CI: 3.3–9.0) with PBO (p<0.001).

Conclusions: In ORATORIO, OCR reduced clinical and MRI disease activity vs PBO, including in patient subgroups with and without T1 Gd⁺lesions at baseline.

Supported by F. Hoffmann-La Roche Ltd.

DX06 Ocrelizumab Efficacy in PPMS Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase III, Placebo-Controlled Trial

DX06
Ocrelizumab Efficacy in PPMS Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase III, Placebo-Controlled Trial