Contributions
Abstract: P676
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Two identical Phase III trials in relapsing multiple sclerosis (RMS; OPERA I [NCT01247324] and OPERA II [NCT01412333]) and the Phase III trial in primary progressive MS (PPMS; ORATORIO [NCT01194570]) evaluated the safety and efficacy of ocrelizumab. Ongoing safety reporting on disease-modifying therapies for MS is crucial to understanding the long-term benefit-risk profile.
Objective: To report safety data from the follow-up of the global clinical trials of ocrelizumab in RMS and PPMS.
Methods: In the OPERA studies, patients with RMS were randomised in a 1:1 ratio to receive intravenous ocrelizumab 600 mg every 24 weeks or subcutaneous interferon beta-1a (IFN β-1a) 44 µg three times weekly for 96 weeks. In the ORATORIO trial, patients with PPMS were randomised in a 2:1 ratio to receive intravenous ocrelizumab 600 mg or placebo every 24 weeks for at least 120 weeks. Following completion of the controlled treatment periods, Phase III patients were eligible to enter the ocrelizumab open-label extension (OLE) phase of the trial. In a Phase II study in relapsing-remitting MS, patients were randomised in a 1:1:1:1 ratio to receive ocrelizumab 600 mg, ocrelizumab 2000 mg, placebo or intramuscular IFN β-1a through Week 24, followed by ocrelizumab every 24 weeks through Week 96. Following a treatment-free period, eligible patients from the Phase II trial entered a long-term OLE in which ocrelizumab 600 mg was administered every 24 weeks. Safety outcomes were reported for all patients administered with ocrelizumab in Phase II and III MS clinical trials, including patients who switched to ocrelizumab from comparators. Long-term safety data will continue to be reported, particularly for serious infections, malignancies and any new signals that could arise.
Results: As of 17 February 2017, 2,301 patients with MS received ocrelizumab, resulting in 7,748 patient-years (PY) of exposure. Reported rates per 100 PY (95% confidence interval) were as follows: adverse events (AEs), 226 (222-229); serious AEs, 7.18 (6.59-7.80); infections, 71.3 (69.5-73.2); and serious infections, 1.86 (1.57-2.19). The incidence rate of malignancy was 0.454 (0.316-0.632).
Conclusions: The updated safety profile in the ocrelizumab MS all-exposure population is generally consistent with that seen during the controlled treatment period in the RMS and PPMS populations. Additional data from the ongoing follow-up will be reported.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
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.
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.
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.
C.J. Guittari is an employee of Genentech, Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd.
C. Li is an employee of F. Hoffmann-La Roche Ltd.
C. Marcillat is an employee of F. Hoffmann-La Roche Ltd.
D. Wormser is an employee and shareholder of F. Hoffmann-La Roche Ltd.
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.
Abstract: P676
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Two identical Phase III trials in relapsing multiple sclerosis (RMS; OPERA I [NCT01247324] and OPERA II [NCT01412333]) and the Phase III trial in primary progressive MS (PPMS; ORATORIO [NCT01194570]) evaluated the safety and efficacy of ocrelizumab. Ongoing safety reporting on disease-modifying therapies for MS is crucial to understanding the long-term benefit-risk profile.
Objective: To report safety data from the follow-up of the global clinical trials of ocrelizumab in RMS and PPMS.
Methods: In the OPERA studies, patients with RMS were randomised in a 1:1 ratio to receive intravenous ocrelizumab 600 mg every 24 weeks or subcutaneous interferon beta-1a (IFN β-1a) 44 µg three times weekly for 96 weeks. In the ORATORIO trial, patients with PPMS were randomised in a 2:1 ratio to receive intravenous ocrelizumab 600 mg or placebo every 24 weeks for at least 120 weeks. Following completion of the controlled treatment periods, Phase III patients were eligible to enter the ocrelizumab open-label extension (OLE) phase of the trial. In a Phase II study in relapsing-remitting MS, patients were randomised in a 1:1:1:1 ratio to receive ocrelizumab 600 mg, ocrelizumab 2000 mg, placebo or intramuscular IFN β-1a through Week 24, followed by ocrelizumab every 24 weeks through Week 96. Following a treatment-free period, eligible patients from the Phase II trial entered a long-term OLE in which ocrelizumab 600 mg was administered every 24 weeks. Safety outcomes were reported for all patients administered with ocrelizumab in Phase II and III MS clinical trials, including patients who switched to ocrelizumab from comparators. Long-term safety data will continue to be reported, particularly for serious infections, malignancies and any new signals that could arise.
Results: As of 17 February 2017, 2,301 patients with MS received ocrelizumab, resulting in 7,748 patient-years (PY) of exposure. Reported rates per 100 PY (95% confidence interval) were as follows: adverse events (AEs), 226 (222-229); serious AEs, 7.18 (6.59-7.80); infections, 71.3 (69.5-73.2); and serious infections, 1.86 (1.57-2.19). The incidence rate of malignancy was 0.454 (0.316-0.632).
Conclusions: The updated safety profile in the ocrelizumab MS all-exposure population is generally consistent with that seen during the controlled treatment period in the RMS and PPMS populations. Additional data from the ongoing follow-up will be reported.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
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.
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.
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.
C.J. Guittari is an employee of Genentech, Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd.
C. Li is an employee of F. Hoffmann-La Roche Ltd.
C. Marcillat is an employee of F. Hoffmann-La Roche Ltd.
D. Wormser is an employee and shareholder of F. Hoffmann-La Roche Ltd.
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.