Contributions
Abstract: P720
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+ B cells. Infusion-related reactions (IRRs) have been observed with the administration of OCR.
Objective: To evaluate the pattern of IRRs in Phase III, randomised, double-blind studies in relapsing multiple sclerosis (RMS; OPERA I and II) and primary progressive MS (PPMS; ORATORIO).
Methods: In the double-blind, double-dummy OPERA studies, patients were randomised (1:1) to OCR 600mg via intravenous (IV) infusion every 24 weeks or subcutaneous interferon beta-1a (IFNβ-1a) 44µg 3-times weekly over 96 weeks. In ORATORIO, patients were randomised (2:1) to OCR 600mg IV given as two 300mg infusions 14 days apart or matching placebo (PBO) every 24 weeks for ≥120 weeks. Patients were pretreated with IV methylprednisolone 100mg or equivalent to maintain blinding; pre-treatment with analgesics/antipyretics and antihistamines were recommended.
Results: Safety analyses included 825 OCR- vs 826 IFNβ-1a‒treated patients in OPERA I and II, and 486 OCR- vs 239 PBO-treated patients in ORATORIO. Proportions of patients with ≥1 IRR were 34.3% with OCR (n=283) vs 9.7% with IFNβ-1a (n=80) in OPERA (over 96 weeks), and 39.9% with OCR (n=194) vs 25.5% with PBO (n=61) in ORATORIO (over ≈3 years); the majority of IRRs were mild to moderate in severity (OCR: 92.6% [n=262] vs IFNβ-1a: 98.8% [n=79] in OPERA; OCR: 96.9% [n=188] vs PBO: 93.4% [n=57] in ORATORIO). The most frequent (≥10%) IRR symptoms with OCR were pruritus, rash, throat irritation and flushing in OPERA, and pruritus, flushing, rash, pyrexia, headache and throat irritation in ORATORIO. IRRs with OCR were highest with first infusion (27.5% [n=227] in OPERA; 27.4% [n=133] in ORATORIO) and decreased with subsequent doses (Dose 2: 13.7% [n=107] in OPERA; 11.6% [n=54] in ORATORIO). Grade 3 IRRs in OPERA were 2.4% with OCR (n=20) vs 0.1% with IFNβ-1a (n=1); n=6 vs 0 were reported post Dose 1. One patient, in the OCR group, had a Grade 4 IRR (bronchospasm). No Grade 4 IRRs were reported in ORATORIO; Grade 3: 1.2% with OCR (n=6) vs 1.7% with PBO (n=4); n=1 vs 4 were reported post Dose 1.
Conclusions: In these Phase III studies in RMS and PPMS, OCR was generally well tolerated. The most common adverse event was IRRs, which were mostly mild to moderate in severity, most frequent with first infusion, manageable with premedication and symptomatic treatment, and decreased in incidence with further infusions.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure:
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.
Douglas 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.
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.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd., Teva, and Sanofi.
Stephen L. Hauser serves on the scientific advisory boards for Annexon, Symbiotix, Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd. for CD20-related meetings and presentations.
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.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care 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 Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis Research Foundation and Roche Research Foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp,
Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd., Genentech, Inc., Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies, and Akros; is co-chief editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
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 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.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme F. Hoffmann-La Roche Ltd. He is a steering committee member for 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.
Peter Chin is an employee and/or shareholder of Genentech, Inc.
Carrie Li is an employee of F. Hoffmann-La Roche Ltd.
Nicole Mairon is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Julie Napieralski is an employee of F. Hoffmann-La Roche Ltd.
Giancarlo Comi has received compensation for consulting services from F. Hoffmann-La Roche Ltd, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Chugai, Receptos, Forward Pharma, and received compensation for speaking activities from F. Hoffmann-La Roche Ltd, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Receptos.
Abstract: P720
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+ B cells. Infusion-related reactions (IRRs) have been observed with the administration of OCR.
Objective: To evaluate the pattern of IRRs in Phase III, randomised, double-blind studies in relapsing multiple sclerosis (RMS; OPERA I and II) and primary progressive MS (PPMS; ORATORIO).
Methods: In the double-blind, double-dummy OPERA studies, patients were randomised (1:1) to OCR 600mg via intravenous (IV) infusion every 24 weeks or subcutaneous interferon beta-1a (IFNβ-1a) 44µg 3-times weekly over 96 weeks. In ORATORIO, patients were randomised (2:1) to OCR 600mg IV given as two 300mg infusions 14 days apart or matching placebo (PBO) every 24 weeks for ≥120 weeks. Patients were pretreated with IV methylprednisolone 100mg or equivalent to maintain blinding; pre-treatment with analgesics/antipyretics and antihistamines were recommended.
Results: Safety analyses included 825 OCR- vs 826 IFNβ-1a‒treated patients in OPERA I and II, and 486 OCR- vs 239 PBO-treated patients in ORATORIO. Proportions of patients with ≥1 IRR were 34.3% with OCR (n=283) vs 9.7% with IFNβ-1a (n=80) in OPERA (over 96 weeks), and 39.9% with OCR (n=194) vs 25.5% with PBO (n=61) in ORATORIO (over ≈3 years); the majority of IRRs were mild to moderate in severity (OCR: 92.6% [n=262] vs IFNβ-1a: 98.8% [n=79] in OPERA; OCR: 96.9% [n=188] vs PBO: 93.4% [n=57] in ORATORIO). The most frequent (≥10%) IRR symptoms with OCR were pruritus, rash, throat irritation and flushing in OPERA, and pruritus, flushing, rash, pyrexia, headache and throat irritation in ORATORIO. IRRs with OCR were highest with first infusion (27.5% [n=227] in OPERA; 27.4% [n=133] in ORATORIO) and decreased with subsequent doses (Dose 2: 13.7% [n=107] in OPERA; 11.6% [n=54] in ORATORIO). Grade 3 IRRs in OPERA were 2.4% with OCR (n=20) vs 0.1% with IFNβ-1a (n=1); n=6 vs 0 were reported post Dose 1. One patient, in the OCR group, had a Grade 4 IRR (bronchospasm). No Grade 4 IRRs were reported in ORATORIO; Grade 3: 1.2% with OCR (n=6) vs 1.7% with PBO (n=4); n=1 vs 4 were reported post Dose 1.
Conclusions: In these Phase III studies in RMS and PPMS, OCR was generally well tolerated. The most common adverse event was IRRs, which were mostly mild to moderate in severity, most frequent with first infusion, manageable with premedication and symptomatic treatment, and decreased in incidence with further infusions.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure:
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.
Douglas 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.
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.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd., Teva, and Sanofi.
Stephen L. Hauser serves on the scientific advisory boards for Annexon, Symbiotix, Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd. for CD20-related meetings and presentations.
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.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care 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 Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis Research Foundation and Roche Research Foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp,
Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd., Genentech, Inc., Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies, and Akros; is co-chief editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
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 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.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme F. Hoffmann-La Roche Ltd. He is a steering committee member for 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.
Peter Chin is an employee and/or shareholder of Genentech, Inc.
Carrie Li is an employee of F. Hoffmann-La Roche Ltd.
Nicole Mairon is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Julie Napieralski is an employee of F. Hoffmann-La Roche Ltd.
Giancarlo Comi has received compensation for consulting services from F. Hoffmann-La Roche Ltd, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Chugai, Receptos, Forward Pharma, and received compensation for speaking activities from F. Hoffmann-La Roche Ltd, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Receptos.