Abstract: P910
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: The efficacy and safety of ocrelizumab (OCR) in primary progressive multiple sclerosis (PPMS) were demonstrated versus placebo (PBO) in the Phase III ORATORIO study (NCT01194570).
Objective: To assess the efficacy of switching to or maintaining OCR therapy on disability progression, confirmed at 24 weeks, in the open-label extension (OLE) phase of ORATORIO.
Methods: For the double-blind period (DBP) of ORATORIO, patients (N=732) were randomised (2:1) to OCR or PBO and followed for ≥120 weeks until a prespecified number of confirmed disability progression (CDP) events occurred. At the end of the DBP, patients remained on blinded treatment as randomised until the outcome of the trial was ascertained (extended controlled period). At the start of the OLE period, patients continued (OCR-OCR) or were switched from PBO to OCR (PBO-OCR). By Week 240, the last patient had entered the OLE. Time to onset of 12- (primary endpoint) and 24-week-CDP (increase from baseline [BL] Expanded Disability Status Scale [CDP-EDSS] score of ≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5) and time to 24-week CDP on the 9-Hole Peg Test (CDP-9HPT, ≥20% increase from BL in the timed 9HPT from BL) were analysed up to Week 264 (all patients had ~2 years of OLE follow-up).
Results: Overall, 72% (527/732) patients entered the OLE. In the DBP, and compared with PBO, OCR reduced the risk of 24-week CDP by 25% (p=0.037) and 24-week CDP-9HPT by 45% (p< 0.001). At Week 168 (12 weeks after the first patients entered the OLE), the proportion of patients with 24-week CDP-EDSS in the PBO-OCR and OCR-OCR groups was 44.7% vs 33.3% (Δ=11.4%; p=0.005), respectively. At Weeks 192 and 264, the corresponding proportions were 49.3% vs 37.8% (Δ=11.5%; p=0.006) and 57.7% vs 48.1% (Δ=9.6%; p=0.023). At Week 168, the proportion of patients with 24-week CDP-9HPT in the PBO-OCR and OCR-OCR groups was 29.7% vs 17.9%, respectively (Δ=11.8%; p=0.001). At Weeks 192 and 264, the corresponding proportions were 32.5% vs 21.6% (Δ=10.9; p=0.005) and 39.5% vs 26.1% (Δ=13.4%; p=0.001).
Conclusions: After 5.5 years (264 weeks) follow-up, the proportion of patients with disability progression in EDSS and 9HPT was lower in patients who initiated OCR treatment earlier (OCR-OCR) compared to patients initially receiving PBO (PBO-OCR), showing that patients initiating OCR between 3-5 years (144-240 weeks) earlier accrued significant and sustained reductions in disability progression compared to patients switching from PBO.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme; royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.
B. Brochet has received research support from Bayer, Merck, Genzyme, Biogen, Novartis, Roche, Actelion, MedDay and Teva, and has consulting agreements with Novartis and Biogen.
X. Montalban has received speaker honoraria and travel expense reimbursement for participation in scientific meetings, been a steering committee member of clinical trials or served on advisory boards of clinical trials for Actelion, Biogen, Celgene, Merck, Novartis, Oryzon, Roche, Sanofi-Genzyme and Teva Pharmaceutical.
R. T. Naismith reports financial relationships with Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Inc., Genzyme, Novartis and Teva.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
M. Garas is an employee and shareholder of F. Hoffmann-La Roche Ltd.
P. Villoslada is an employee of Genentech, Inc.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
S. Hubeaux is an employee and shareholder of F. Hoffmann-La Roche Ltd.
L. Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products; the Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
S. L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
Abstract: P910
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: The efficacy and safety of ocrelizumab (OCR) in primary progressive multiple sclerosis (PPMS) were demonstrated versus placebo (PBO) in the Phase III ORATORIO study (NCT01194570).
Objective: To assess the efficacy of switching to or maintaining OCR therapy on disability progression, confirmed at 24 weeks, in the open-label extension (OLE) phase of ORATORIO.
Methods: For the double-blind period (DBP) of ORATORIO, patients (N=732) were randomised (2:1) to OCR or PBO and followed for ≥120 weeks until a prespecified number of confirmed disability progression (CDP) events occurred. At the end of the DBP, patients remained on blinded treatment as randomised until the outcome of the trial was ascertained (extended controlled period). At the start of the OLE period, patients continued (OCR-OCR) or were switched from PBO to OCR (PBO-OCR). By Week 240, the last patient had entered the OLE. Time to onset of 12- (primary endpoint) and 24-week-CDP (increase from baseline [BL] Expanded Disability Status Scale [CDP-EDSS] score of ≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5) and time to 24-week CDP on the 9-Hole Peg Test (CDP-9HPT, ≥20% increase from BL in the timed 9HPT from BL) were analysed up to Week 264 (all patients had ~2 years of OLE follow-up).
Results: Overall, 72% (527/732) patients entered the OLE. In the DBP, and compared with PBO, OCR reduced the risk of 24-week CDP by 25% (p=0.037) and 24-week CDP-9HPT by 45% (p< 0.001). At Week 168 (12 weeks after the first patients entered the OLE), the proportion of patients with 24-week CDP-EDSS in the PBO-OCR and OCR-OCR groups was 44.7% vs 33.3% (Δ=11.4%; p=0.005), respectively. At Weeks 192 and 264, the corresponding proportions were 49.3% vs 37.8% (Δ=11.5%; p=0.006) and 57.7% vs 48.1% (Δ=9.6%; p=0.023). At Week 168, the proportion of patients with 24-week CDP-9HPT in the PBO-OCR and OCR-OCR groups was 29.7% vs 17.9%, respectively (Δ=11.8%; p=0.001). At Weeks 192 and 264, the corresponding proportions were 32.5% vs 21.6% (Δ=10.9; p=0.005) and 39.5% vs 26.1% (Δ=13.4%; p=0.001).
Conclusions: After 5.5 years (264 weeks) follow-up, the proportion of patients with disability progression in EDSS and 9HPT was lower in patients who initiated OCR treatment earlier (OCR-OCR) compared to patients initially receiving PBO (PBO-OCR), showing that patients initiating OCR between 3-5 years (144-240 weeks) earlier accrued significant and sustained reductions in disability progression compared to patients switching from PBO.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme; royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.
B. Brochet has received research support from Bayer, Merck, Genzyme, Biogen, Novartis, Roche, Actelion, MedDay and Teva, and has consulting agreements with Novartis and Biogen.
X. Montalban has received speaker honoraria and travel expense reimbursement for participation in scientific meetings, been a steering committee member of clinical trials or served on advisory boards of clinical trials for Actelion, Biogen, Celgene, Merck, Novartis, Oryzon, Roche, Sanofi-Genzyme and Teva Pharmaceutical.
R. T. Naismith reports financial relationships with Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Inc., Genzyme, Novartis and Teva.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
M. Garas is an employee and shareholder of F. Hoffmann-La Roche Ltd.
P. Villoslada is an employee of Genentech, Inc.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
S. Hubeaux is an employee and shareholder of F. Hoffmann-La Roche Ltd.
L. Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products; the Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
S. L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.