Contributions
Abstract: 192
Type: Oral
Abstract Category: Therapy - disease modifying - Neurorepair
Background: Opicinumab (BIIB033), a human monoclonal antibody, was genetically engineered to have low effector function, and blocks LINGO-1, a CNS-specific negative regulator of myelination and axonal regeneration. Opicinumab was effective and well tolerated in preclinical models of remyelination/Phase 1 studies, respectively, and in the Phase 2a proof of biology RENEW study resulted in evidence of enhanced remyelination in participants with a first episode of acute optic neuritis.
Goals: Evaluate the efficacy of opicinumab vs placebo in disabled participants with relapsing MS active over the previous year when used chronically and concurrently with intramuscular (IM) interferon (IFN) beta-1a.
Methods: SYNERGY (NCT01864148) is a recently completed randomised, double-blind, placebo-controlled, dose-ranging proof-of-concept study. Participants (18-58 y) with active RRMS or SPMS over the previous year were randomised to intravenous 3, 10, 30 or 100 mg/kg opicinumab or placebo every 4 weeks for 19 doses with IM IFN beta-1a 30 mcg once weekly for 72-84 weeks to treat the inflammatory component, and assessed for 84 weeks. The primary endpoint is the percentage of participants experiencing confirmed improvement of neurophysical and/or cognitive function over 72 weeks measured by a composite comprising the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and 3-Second Paced Auditory Serial Addition Test (PASAT-3); improvement is defined as a ≥1.0 point decrease in EDSS (from baseline ≤6.0) and/or ≥15% improvement from baseline in T25FW, 9HPT or PASAT-3, all confirmed for ≥3 months. Secondary efficacy endpoints include percentage with 3 month confirmed worsening of neurophysical and/or cognitive function and/or disability over 72 weeks, based on EDSS, T25FW, 9HPT and PASAT-3. Other clinical efficacy endpoints include MS-COG, 6-Minute Walk Test, Scripps Neurological Rating Scale and patient-reported outcomes.
Results: 418 participants, 330 with RRMS and 88 with SPMS, were randomised; 330 completed the study. Details of the primary, secondary, and other clinical efficacy outcomes will be presented for the first time.
Conclusions: SYNERGY results will determine the potential efficacy of opicinumab for improving pre-existing disability and/or preventing further disease worsening in disabled participants with relapsing MS via enhancing CNS repair when used concurrently with IM IFN beta-1a to control the inflammatory component.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA).
Diego Cadavid, Richard Rudick, Adama Ibrahim, Yiwei Zhang and Lei Xu: employees of and stockholders in Biogen.
Keith Edwards: consulting fees and speaker bureaus for Biogen and Genzyme; research support from Actelion, Biogen, Eisai, Eli Lilly, Forum Pharmaceuticals, Genentech, Genzyme/Sanofi, Hoffman-La Roche, Merz Pharmaceuticals, Novartis, Pfizer and Vaccinex.
Raymond Hupperts: advisor/speaker/consultant for Biogen, Merck Serono, Novartis, and Sanofi-Aventis, research support from Biogen and Merck Serono.
Jelena Drulović: advisor/speaker for Bayer HealthCare, Genzyme, Medis, Merck, Novartis, and Sanofi-Aventis, research support from the Ministry of Education and Science, Republic of Serbia (project no. 175031).
Xavier Montalban: speaker fees/travel expense reimbursement from and steering committees/advisory boards for Actelion, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck, NeuroTec, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis, Teva and Trophos.
Hans-Peter Hartung: speaker fees/travel expense reimbursement from and steering committees/advisory boards for Biogen, Geneuro, Genzyme, Merck, Medimmune, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis and Teva.
Bruno Brochet: advisory boards for and he/his institution has received honoraria from Bayer HealthCare, Genzyme, Novartis, Roche, and Teva, research support for his institution from Bayer HealthCare, Biogen, Genzyme, MedDay, Novartis and Roche.
Peter Calabresi: compensation for consulting from Vertex; research support to Johns Hopkins from Biogen, MedImmune and Novartis.
Biogen provided funding for medical writing support in the development of this abstract. Becky Gardner PhD (Excel Scientific Solutions, Horsham, UK) wrote the first draft of the abstract based on input from authors. Biogen reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract, and provided their final approval of all content.
Abstract: 192
Type: Oral
Abstract Category: Therapy - disease modifying - Neurorepair
Background: Opicinumab (BIIB033), a human monoclonal antibody, was genetically engineered to have low effector function, and blocks LINGO-1, a CNS-specific negative regulator of myelination and axonal regeneration. Opicinumab was effective and well tolerated in preclinical models of remyelination/Phase 1 studies, respectively, and in the Phase 2a proof of biology RENEW study resulted in evidence of enhanced remyelination in participants with a first episode of acute optic neuritis.
Goals: Evaluate the efficacy of opicinumab vs placebo in disabled participants with relapsing MS active over the previous year when used chronically and concurrently with intramuscular (IM) interferon (IFN) beta-1a.
Methods: SYNERGY (NCT01864148) is a recently completed randomised, double-blind, placebo-controlled, dose-ranging proof-of-concept study. Participants (18-58 y) with active RRMS or SPMS over the previous year were randomised to intravenous 3, 10, 30 or 100 mg/kg opicinumab or placebo every 4 weeks for 19 doses with IM IFN beta-1a 30 mcg once weekly for 72-84 weeks to treat the inflammatory component, and assessed for 84 weeks. The primary endpoint is the percentage of participants experiencing confirmed improvement of neurophysical and/or cognitive function over 72 weeks measured by a composite comprising the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and 3-Second Paced Auditory Serial Addition Test (PASAT-3); improvement is defined as a ≥1.0 point decrease in EDSS (from baseline ≤6.0) and/or ≥15% improvement from baseline in T25FW, 9HPT or PASAT-3, all confirmed for ≥3 months. Secondary efficacy endpoints include percentage with 3 month confirmed worsening of neurophysical and/or cognitive function and/or disability over 72 weeks, based on EDSS, T25FW, 9HPT and PASAT-3. Other clinical efficacy endpoints include MS-COG, 6-Minute Walk Test, Scripps Neurological Rating Scale and patient-reported outcomes.
Results: 418 participants, 330 with RRMS and 88 with SPMS, were randomised; 330 completed the study. Details of the primary, secondary, and other clinical efficacy outcomes will be presented for the first time.
Conclusions: SYNERGY results will determine the potential efficacy of opicinumab for improving pre-existing disability and/or preventing further disease worsening in disabled participants with relapsing MS via enhancing CNS repair when used concurrently with IM IFN beta-1a to control the inflammatory component.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA).
Diego Cadavid, Richard Rudick, Adama Ibrahim, Yiwei Zhang and Lei Xu: employees of and stockholders in Biogen.
Keith Edwards: consulting fees and speaker bureaus for Biogen and Genzyme; research support from Actelion, Biogen, Eisai, Eli Lilly, Forum Pharmaceuticals, Genentech, Genzyme/Sanofi, Hoffman-La Roche, Merz Pharmaceuticals, Novartis, Pfizer and Vaccinex.
Raymond Hupperts: advisor/speaker/consultant for Biogen, Merck Serono, Novartis, and Sanofi-Aventis, research support from Biogen and Merck Serono.
Jelena Drulović: advisor/speaker for Bayer HealthCare, Genzyme, Medis, Merck, Novartis, and Sanofi-Aventis, research support from the Ministry of Education and Science, Republic of Serbia (project no. 175031).
Xavier Montalban: speaker fees/travel expense reimbursement from and steering committees/advisory boards for Actelion, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck, NeuroTec, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis, Teva and Trophos.
Hans-Peter Hartung: speaker fees/travel expense reimbursement from and steering committees/advisory boards for Biogen, Geneuro, Genzyme, Merck, Medimmune, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis and Teva.
Bruno Brochet: advisory boards for and he/his institution has received honoraria from Bayer HealthCare, Genzyme, Novartis, Roche, and Teva, research support for his institution from Bayer HealthCare, Biogen, Genzyme, MedDay, Novartis and Roche.
Peter Calabresi: compensation for consulting from Vertex; research support to Johns Hopkins from Biogen, MedImmune and Novartis.
Biogen provided funding for medical writing support in the development of this abstract. Becky Gardner PhD (Excel Scientific Solutions, Horsham, UK) wrote the first draft of the abstract based on input from authors. Biogen reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract, and provided their final approval of all content.