Early Onset of Action with Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine (P4.102)

Objective: Assess the early onset of action of fremanezumab in the prevention of chronic migraine. Background: Migraine prevention, with earlier onset of action, could increase benefit to migraine patients. Fremanezumab is a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP). Design/Methods: 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing the efficacy, safety, and tolerability of 2 subcutaneous dose regimens of fremanezumab and placebo in adults with chronic migraine (CM). Patients were randomly assigned to 1 of 3 treatment groups: (1)monthly dosing: 675 mg fremanezumab followed by 225 mg fremanezumab at months 2 and 3, (2)quarterly dosing: 675 mg fremanezumab at month 1, followed by placebo injections at months 2 and 3, and (3)monthly administration of matching placebo. The primary efficacy endpoint, mean change from baseline to the 12-week treatment period in monthly average number of migraine days, was analyzed using an ANCOVA or the Wilcoxon rank sum test. Mean change from baseline to weeks 1–4, after 1 st dose was analyzed using a mixed-effect model for repeated measures. Results: Statistically significant reduction in number of monthly headache days of at least moderate severity was experienced during the 12-week period after 1st dose for both fremanezumab dosing regimens [monthly(−4.6 days);quarterly(−4.3 days); p Week 1, (−1.1 days; p Week 4, (−1.1 days; p=0.0006) versus placebo (−0.7 days) Posthoc analysis indicated more patients reported no headache of at least moderate severity [fremanezumab(69%; p=0.0036) versus placebo(61%)] by the next day following first injection. Conclusions: Onset of action with fremanezumab occurred rapidly for preventive treatment of migraine and significant improvement was maintained for both dosing regimens. Disclosure: Dr. Yeung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Aycardi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Bigal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Blankenbiller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Grozinski-Wolff has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Yang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Ma, MS has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva for employment. Dr. Brandes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards: Amgen, Lilly, Promius, Supernus; consulting for Amgen, Promius. Dr. Brandes has received research support from Amgen, Teva, Allergan, Colucid, Zotrip.