Abstract
Objective: To evaluate the efficacy of opicinumab (anti-LINGO-1; BIIB033) in participants with relapsing multiple sclerosis (MS) when used concurrently with intramuscular (IM) interferon (IFN) beta-1a.
Background: Opicinumab blocks LINGO-1, a negative regulator of myelination and axonal regeneration, and is a candidate reparative therapy for MS.
Design/Methods: SYNERGY (NCT01864148) is a double-blind, dose-ranging proof-of-concept study. Participants aged 18–58 years with a baseline Expanded Disability Status Scale (EDSS) score 2.0–6.0 and active relapsing-remitting or secondary progressive MS were randomized to intravenous opicinumab (3, 10, 30 or 100 mg/kg) or placebo every 4 weeks for 19 doses. All participants received concurrent treatment with IM IFN beta-1a 30 mcg once weekly. The primary endpoint was the percentage of participants with ≥3 month confirmed improvement of neurophysical and/or cognitive function over 72 weeks measured by a multicomponent endpoint comprising the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test and 3-Second Paced Auditory Serial Addition Test. Analysis for the primary endpoint used logistic regression and a linear trend test to assess dose response.
Results: A total of 418 participants were randomized and dosed; 334 completed the study. The linear trend test for the primary endpoint was not statistically significant (P=0.8931). Pairwise comparison of each dose arm to placebo showed an inverted U-shaped dose-response: the estimated percentage of improvement responders was 51.6% for placebo, 51.1% for 3 mg/kg opicinumab (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.46–2.07), 65.6% for 10 mg/kg (OR 1.79; 95% CI 0.97–3.31), 68.8% for 30 mg/kg (OR 2.06; 95% CI 1.11–3.84) and 41.2% for 100 mg/kg (OR 0.66; 95% CI 0.36–1.21).
Conclusions: The pre-specified primary endpoint was not met. Results revealed an increased percentage of improvement responders in opicinumab-treated arms vs placebo at 10 and 30 mg/kg, with an inverted U-shaped dose-response.
Study Supported by: Biogen
Disclosure: Dr. Mellion has received personal compensation for activities with Biogen has an employee. Dr. Mellion holds stock and/or stock options with Biogen. Dr. Edwards has received personal compensation for activities with Biogen and Sanofi Genzyme as a speaker and/or consultant. Dr. Edwards has received research support from Biogen, Genentech, Sanofi-Genzyme, and Hoffmann-La Roche. Dr. Hupperts has received personal compensation for activities with Biogen, Merck Serono, Novartis, Sanofi-Aventis as a speaker. Dr. Hupperts has received research support from Biogen and Merck Serono. Dr. Drulovic has received personal compensation for activities with Bayer HealthCare, Genzyme, Medis, Merck, Novartis, and Sanofi-Aventis as a speaker and/or advisor. Dr. Drulovic has received research support from the Ministry of Education and Science, Republic of Serbia. Dr. Montalban has received personal compensation for activities with Almirall, Bayer, Biogen, Celgene, Sanofi Genzyme, Merck, Novartis, Roche, and Teva Pharmaceutical. Dr. Hartung has received personal compensation from Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme as a speaker and consultant. Dr. Brochet has received personal compensation for activities with for Biogen, Genzyme, Merck-Serono, Novartis and Roche for advisory boards. Dr. Calabresi has received personal compensation for activities with Biogen and Vertex as a consultant. Dr. Calabresi has received research support from Biogen, MedImmune, Novartis and Teva. Dr. Rudick has received personal compensation for activities with Biogen Idec. Dr. Rudick holds stock and/or stock options in Biogen Idec. Dr. Ibrahim has received personal compensation for activities with Biogen Idec. Dr. Ibrahim holds stock and/or stock options in Biogen Idec. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Zhang holds stock and/or stock options in Biogen Idec. Dr. Xu has received personal compensation for activities with Biogen as an employee. Dr. Xu hold stock and/or stock options in Biogen. Dr. Cadavid has received personal compensation for activities with Biogen as a holder of stock and/or stock options and as an employee. Dr. SYNERGY investigators has nothing to disclose.
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