Contributions
Abstract: P675
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Background: Current relapsing MS therapies reduce the risk of disease activity/progression related to inflammation while tissue reparative treatments remain an unmet need. Opicinumab (anti-LINGO-1; BIIB033) is a human monoclonal antibody candidate MS reparative agent that blocks LINGO-1, a CNS-specific negative regulator of myelination and neuroaxonal regeneration. A Phase 2a proof of biology study (RENEW) assessing participants with acute optic neuritis showed evidence of remyelination with opicinumab, and was well-tolerated with a similar frequency of adverse events as placebo.
Goals: Assess the safety/tolerability of opicinumab vs placebo in participants with relapsing MS when used chronically and concurrently with interferon (IFN) beta-1a.
Methods: SYNERGY (NCT01864148) is a recently completed randomised, multicentre, double-blind, placebo-controlled study. Eligible participants were aged 18-58 y and had a diagnosis of RRMS (2005 McDonald criteria) or SPMS (Lublin and Reingold criteria) with disease activity in the previous year. Disease activity for RRMS was defined as ≥2 distinct episodes of: clinical relapse, gadolinium-positive (Gd+) lesion or new T2 lesion on brain/spinal cord MRI; for SPMS it was ≥1 occurrences of clinical relapse or Gd+ lesion on brain/spinal cord MRI. Enrolled participants were randomised to 3, 10, 30 or 100 mg/kg opicinumab intravenous or placebo (ratio 1:2:2:2:2) every 4 weeks (total=19 doses), also received IFN beta-1a 30 mcg intramuscular once weekly for 72-84 weeks, and were followed for 84 weeks. The parameters used to assess safety were: adverse events, serious adverse events, clinical laboratory test results (haematology, blood chemistry and urinalysis), physical examination findings, electrocardiogram, vital signs results, weight, serum antibodies to opicinumab, disease activity by brain MRI metrics, MS signs and symptoms, annualised relapse rate, concomitant medication use, and Columbia Suicide Severity Rating Scale score.
Results: Individuals were screened at 72 sites in 12 countries and 330 participants with RRMS and 88 with SPMS (N=418) were randomised; 330 completed the study. Details of the safety/tolerability of opicinumab will be presented.
Conclusions: Safety/tolerability information is important for the ongoing clinical development of opicinumab; SYNERGY will provide valuable data, including the most suitable dose to use in potential future trials, based on efficacy, safety and tolerability assessments.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA).
Stefanie Freeman, Yiwei Zhang, Lei Xu, Michelle Mellion and Diego Cadavid: employees of and stockholders in Biogen.
Krzysztof Selmaj: consultant/speaker for Biogen, Genzyme, Novartis, Ono, Roche, Synthon, and Teva.
Oscar Fernandez: consulting/advisor fees and research support from Actelion, Allergan, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva.
Luigi Grimaldi: serves on a scientific advisory board for Merck Serono; has received funding for travel or speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd. and Bayer HealthCare; and receives institutional research support from Biogen and the Serono Foundation.
Eli Silber and/or his unit has received support and/or speaker/consulting fees from the following companies: Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche and Teva.
Gabriel Pardo: consultant/speaker for Biogen, EMD Serono, Genentech, Genzyme/Sanofi, Novartis and Teva.
S. Mitchell Freedman: serves on advisory boards for Biogen, Genentech, Genzyme, Novartis and Teva, and is on the adjunct faculty (non-reimbursed position) of the University of North Carolina, Chapel Hill.
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: P675
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Background: Current relapsing MS therapies reduce the risk of disease activity/progression related to inflammation while tissue reparative treatments remain an unmet need. Opicinumab (anti-LINGO-1; BIIB033) is a human monoclonal antibody candidate MS reparative agent that blocks LINGO-1, a CNS-specific negative regulator of myelination and neuroaxonal regeneration. A Phase 2a proof of biology study (RENEW) assessing participants with acute optic neuritis showed evidence of remyelination with opicinumab, and was well-tolerated with a similar frequency of adverse events as placebo.
Goals: Assess the safety/tolerability of opicinumab vs placebo in participants with relapsing MS when used chronically and concurrently with interferon (IFN) beta-1a.
Methods: SYNERGY (NCT01864148) is a recently completed randomised, multicentre, double-blind, placebo-controlled study. Eligible participants were aged 18-58 y and had a diagnosis of RRMS (2005 McDonald criteria) or SPMS (Lublin and Reingold criteria) with disease activity in the previous year. Disease activity for RRMS was defined as ≥2 distinct episodes of: clinical relapse, gadolinium-positive (Gd+) lesion or new T2 lesion on brain/spinal cord MRI; for SPMS it was ≥1 occurrences of clinical relapse or Gd+ lesion on brain/spinal cord MRI. Enrolled participants were randomised to 3, 10, 30 or 100 mg/kg opicinumab intravenous or placebo (ratio 1:2:2:2:2) every 4 weeks (total=19 doses), also received IFN beta-1a 30 mcg intramuscular once weekly for 72-84 weeks, and were followed for 84 weeks. The parameters used to assess safety were: adverse events, serious adverse events, clinical laboratory test results (haematology, blood chemistry and urinalysis), physical examination findings, electrocardiogram, vital signs results, weight, serum antibodies to opicinumab, disease activity by brain MRI metrics, MS signs and symptoms, annualised relapse rate, concomitant medication use, and Columbia Suicide Severity Rating Scale score.
Results: Individuals were screened at 72 sites in 12 countries and 330 participants with RRMS and 88 with SPMS (N=418) were randomised; 330 completed the study. Details of the safety/tolerability of opicinumab will be presented.
Conclusions: Safety/tolerability information is important for the ongoing clinical development of opicinumab; SYNERGY will provide valuable data, including the most suitable dose to use in potential future trials, based on efficacy, safety and tolerability assessments.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA).
Stefanie Freeman, Yiwei Zhang, Lei Xu, Michelle Mellion and Diego Cadavid: employees of and stockholders in Biogen.
Krzysztof Selmaj: consultant/speaker for Biogen, Genzyme, Novartis, Ono, Roche, Synthon, and Teva.
Oscar Fernandez: consulting/advisor fees and research support from Actelion, Allergan, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva.
Luigi Grimaldi: serves on a scientific advisory board for Merck Serono; has received funding for travel or speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd. and Bayer HealthCare; and receives institutional research support from Biogen and the Serono Foundation.
Eli Silber and/or his unit has received support and/or speaker/consulting fees from the following companies: Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche and Teva.
Gabriel Pardo: consultant/speaker for Biogen, EMD Serono, Genentech, Genzyme/Sanofi, Novartis and Teva.
S. Mitchell Freedman: serves on advisory boards for Biogen, Genentech, Genzyme, Novartis and Teva, and is on the adjunct faculty (non-reimbursed position) of the University of North Carolina, Chapel Hill.
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.