Abstract: P1234
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: Ocrelizumab (OCR), an FDA-approved humanised monoclonal antibody that selectively targets CD20+ B cells, had superior efficacy versus placebo (PBO) in patients with primary progressive multiple sclerosis (PPMS) in the double-blind period (DBP; cut-off 24 July 2015) of the Phase III ORATORIO study (NCT01194570). The primary endpoint was 12-week confirmed disability progression (CDP). At the end of the DBP, patients remained on treatment as originally randomised and remained blinded to treatment assignment. After ascertaining that the study was positive, sites were unblinded (12 October 2015) and patients could enter the open-label extension (OLE). The extended controlled treatment period (ECP) ranged from randomisation until the first OLE dose, and was completed when the last patient entered OLE (27 April 2016).
Objective: To evaluate the effects of OCR vs PBO on disability progression during the ECP of ORATORIO.
Methods: Patients were randomised (2:1) to OCR 600 mg or PBO every 24 weeks for ≥120 weeks until a prespecified number of CDP events occurred during the DBP. Time to onset of CDP from baseline (BL) sustained for at least 12 or 24 weeks, a composite 12/24-week CDP (cCDP; defined as time to first onset of either CDP, or ≥20% increases in timed 25-foot walk test [T25FW] or 9-hole peg test) and confirmed (12-/24-week) 20% increase in T25FW were evaluated. CDP was defined as an increase from BL Expanded Disability Status Scale (EDSS) score (≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5).
Results: Data from 488 OCR and 244 PBO randomised patients were analysed. Relative risk reductions (RRRs) with OCR vs PBO seen in the DBP for 12- and 24-week CDP (24% [p=0.032] and 25% [p=0.037]) slightly increased in the ECP (25% [p=0.020] and 30% [p=0.005]). Comparable increases in 12- and 24-week cCDP RRRs from the DBP (26% [p=0.001] and 29% [p< 0.001]) were also seen during the ECP (27% [p< 0.001] and 30% [p< 0.001]). Further, the RRRs associated with OCR vs PBO during the DBP for ≥20% worsening in T25FW with 12 or 24-week confirmation (25% [p=0.005] and 27% [p=0.006]) remained consistent overall during the ECP (24% [p=0.008] and 28% [p=0.002]).
Conclusions: The significant and clinically meaningful benefit in reducing disability progression by OCR in patients with PPMS in the ORATORIO study continues to accrue and is durable with ongoing treatment.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
X. 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.
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.
F. Model is an employee and shareholder of F. Hoffmann-La Roche Ltd.
G. Deol-Bhullar is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos,
F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; license fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
Abstract: P1234
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: Ocrelizumab (OCR), an FDA-approved humanised monoclonal antibody that selectively targets CD20+ B cells, had superior efficacy versus placebo (PBO) in patients with primary progressive multiple sclerosis (PPMS) in the double-blind period (DBP; cut-off 24 July 2015) of the Phase III ORATORIO study (NCT01194570). The primary endpoint was 12-week confirmed disability progression (CDP). At the end of the DBP, patients remained on treatment as originally randomised and remained blinded to treatment assignment. After ascertaining that the study was positive, sites were unblinded (12 October 2015) and patients could enter the open-label extension (OLE). The extended controlled treatment period (ECP) ranged from randomisation until the first OLE dose, and was completed when the last patient entered OLE (27 April 2016).
Objective: To evaluate the effects of OCR vs PBO on disability progression during the ECP of ORATORIO.
Methods: Patients were randomised (2:1) to OCR 600 mg or PBO every 24 weeks for ≥120 weeks until a prespecified number of CDP events occurred during the DBP. Time to onset of CDP from baseline (BL) sustained for at least 12 or 24 weeks, a composite 12/24-week CDP (cCDP; defined as time to first onset of either CDP, or ≥20% increases in timed 25-foot walk test [T25FW] or 9-hole peg test) and confirmed (12-/24-week) 20% increase in T25FW were evaluated. CDP was defined as an increase from BL Expanded Disability Status Scale (EDSS) score (≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5).
Results: Data from 488 OCR and 244 PBO randomised patients were analysed. Relative risk reductions (RRRs) with OCR vs PBO seen in the DBP for 12- and 24-week CDP (24% [p=0.032] and 25% [p=0.037]) slightly increased in the ECP (25% [p=0.020] and 30% [p=0.005]). Comparable increases in 12- and 24-week cCDP RRRs from the DBP (26% [p=0.001] and 29% [p< 0.001]) were also seen during the ECP (27% [p< 0.001] and 30% [p< 0.001]). Further, the RRRs associated with OCR vs PBO during the DBP for ≥20% worsening in T25FW with 12 or 24-week confirmation (25% [p=0.005] and 27% [p=0.006]) remained consistent overall during the ECP (24% [p=0.008] and 28% [p=0.002]).
Conclusions: The significant and clinically meaningful benefit in reducing disability progression by OCR in patients with PPMS in the ORATORIO study continues to accrue and is durable with ongoing treatment.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
X. 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.
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.
F. Model is an employee and shareholder of F. Hoffmann-La Roche Ltd.
G. Deol-Bhullar is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos,
F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; license fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.