Interim Analysis of 2-year Clinical Efficacy and Safety of Peginterferon Beta-1a in Patients with Relapsing-Remitting Multiple Sclerosis: Data from the Pivotal Phase 3 ADVANCE Study (S4.005)

OBJECTIVE: To evaluate interim 2-year efficacy and safety of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS) in the on-going Phase 3, ADVANCE study. BACKGROUND: At Year 1 of ADVANCE, peginterferon beta-1a (125 µg subcutaneous every 2 [Q2W] or 4 [Q4W] weeks) significantly improved primary and secondary clinical and magnetic resonance imaging endpoints versus placebo; similar safety profiles were observed across regimens, which reflected that of established interferon beta-1a therapies. DESIGN/METHODS: During Year 2 all patients (18-65 years; Expanded Disability Status Scale score ≤5) received dose-blinded peginterferon beta-1a (at the end of Year 1 patients on placebo were re-randomized to peginterferon beta-1a 125 µg Q2W or Q4W). Interim analyses of 2-year efficacy and safety were conducted for patients with available data over 2 years at cut-off. Post-hoc analyses compared the efficacy of Q2W versus Q4W regimens. RESULTS: For patients continuing peginterferon beta-1a in Year 2, ARR was maintained (for Q4W) or further numerically reduced (for Q2W) relative to Year 1. New or newly-enlarging T2 lesions were numerically lower in Year 2 versus Year 1 for patients continuing Q2W and Q4W. Versus those originally assigned to placebo, reductions in ARR, risk of relapse and disability progression were seen for patients on peginterferon beta-1a during both Years 1 and 2. Peginterferon beta-1a Q2W provided numerically larger treatment effects over 2 years versus Q4W (ARR rate ratio [95% CI]: 0.793 [0.623, 1.00], p=0.059; time to first relapse hazard ratio: 0.81 [0.64, 1.04], p=0.1006; disability progression hazard ratio: 0.89 [0.58, 1.35], p=0.57; T2 lesion mean ratio: 0.36 [0.27, 0.49], p<0.0001; gadolinium-enhancing lesion odds ratio: 0.34 [0.19, 0.61], p=0.0004). Over 2 years peginterferon beta-1a was well tolerated, with a safety profile consistent with Year 1 and other beta interferons. CONCLUSIONS: Interim 2-year results support the maintained benefits of peginterferon beta-1a beyond 1 year in RRMS, with numerically greater efficacy seen for Q2W versus Q4W across the endpoints studied. Study Sponsored by: Biogen Idec Inc. Disclosure: Dr. Deykin has received personal compensation for activities with Biogen Idec as an employee. Dr. Deykin holds stock and/or stock options in Biogen Idec. Dr. Arnold has received personal compensation for activities with Acorda Therapeutics, Bayer Pharmaceuticals Corporation, Biogen Idec, Coronado Biosciences, EMD Serono, Genentech Inc., Genzyme Corporation, GlaxoSmithKline Inc., MedImmune, NeuroRx Research. Dr. Arnold has received research support from Bayer Pharmaceuticals Corporation. Dr. Hung has received personal compensation for activities with Biogen Idec. Dr. Hung holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Hung was involved as an investigator. Dr. Sheikh has received personal compensation for activities with Biogen Idec as an employee. Dr. Sheikh holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Sheikh was involved as an investigator. Dr. Seddighzadeh has received personal compensation for activities with Biogen Idec. Dr. Seddighzadeh holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Seddighzadeh was involved as an investigator. Dr. Zhu has received personal compensation for activities with Biogen Idec as an employee. Dr. Zhu holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Zhu was involved as an investigator. Dr. Zhu holds stock and/or stock options in Elan. Dr. Liu has received personal compensation for activities with Biogen Idec as an employee. Dr. Kieseier has received personal compensation for activities with Bayer Pharmaceuticals Corp., Schering AG, Biogen Idec, Merck Serono, Novartis, Roche Diagnostics Corp., Sanofi-Aventis Pharmaceuticals Inc., and Teva Neuroscience. Dr Kieseier has received research support from Bayer Schering, Biogen Idec, Merck Serono, and Teva Neuroscience.