The Impact of Fremanezumab on Headache-Related Disability in Patients with Episodic Migraine using the Migraine Disability Assessment (P4.095)

Objective: To assess the effect of fremanezumab versus placebo on headache-related disability using the MIDAS questionnaire. Background: Episodic migraine(EM), attacks on ≤15 days per month, has a risk for progression to chronic migraine and affects daily functioning. In clinical trials, fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa), selectively targets calcitonin gene-related peptide ligand, reduced headache frequency in EM patients. The impact of migraine is evaluated utilizing the Migraine Disability Assessment (MIDAS), a validated questionnaire, to assess disability in migraine patients. Design/Methods: 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in adults with EM(TV48125-CNS-30050), randomized 1:1:1 ratio to 1 of 3 treatment groups: (1)monthly dosing: 225 mg fremanezumab at months 1, 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. As a secondary endpoint, changes in MIDAS scores were evaluated from baseline to 4 weeks after last dose. Efficacy analyses were performed in the full analysis set (FAS; all randomized patients receiving ≥1 dose and having ≥10 days of post-baseline primary endpoint assessments, N = 865), and repeated for the per-protocol analysis set (PPS; all patients completing the study without violation of eligibility criteria or omission of drug administration, N =847). Results: A total of 875 patients were randomly assigned to fremanezumab quarterly ( n =291), fremanezumab monthly (n=290), or placebo ( n =294). Least square mean (± standard error) changes from baseline in MIDAS score were larger for fremanezumab (quarterly:−23.0±1.6; monthly: −24.6±1.6) than for placebo (−17.5±1.6), resulting in significant treatment differences (quarterly: −5.4±1.8, P =.002; monthly: −7.0±1.8, P P =.003; monthly: −7.3±1.8 points, P Conclusions: In this Phase 3 study, fremanezumab treatment demonstrated a significant improvement in headache-related disability in patients with EM. Disclosure: Dr. Winner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees/honoraria from Allergan, Amgen, Supernus, has served on the speaker’s bureau for Allergan, Avanir, Supernus. Dr. Winner has received research support from Allergan, Amgen, NuPathe, AstraZeneca, Avanir, Eli Lilly, Novartis. Dr. Fitzgerald, PhD has nothing to disclose. Dr. Gandhi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Yeung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals. Dr. Cohen 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. Aycardi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceuticals.