• Timothy R Smith, Marina Janelidze, George Chakhava, Roger Cady, Joe Hirman, Brent Allan, Susan Pederson, Jeff Smith, and Barbara Schaeffler.
• StudyMetrix Research, St. Peters, MO, USA. Electronic address: tsmith@studymetrix.com.
• Clin Ther. 2020 Dec 1; 42 (12): 2254-2265.e3.

PurposeThe Prevention of Migraine via Intravenous ALD403 Safety and Efficacy 1 (PROMISE-1) study was a phase III, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, tolerability, and pharmacokinetic properties of repeat intravenous (IV) doses of the calcitonin gene-related peptide‒targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with episodic migraine. Here we present the results of PROMISE-1 through 1 year of treatment (up to 4 doses).MethodsPatients received up to 4 IV administrations of eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks. Patients recorded migraine and headache in an electronic diary daily. Additional assessments, including the patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 56-week study period.FindingsA total of 888 adults (mean age, 39.8 years; 84.3% female; 83.8% white) received treatment: eptinezumab 30 mg, n = 219; eptinezumab 100 mg, n = 223; eptinezumab 300 mg, n = 224; and placebo, n = 222. During the primary 12-week study evaluation period, single doses of eptinezumab 100 mg and 300 mg led to significant reductions in mean monthly migraine-days versus placebo, beginning as early as the first day after the initial dose. The reduction in mean monthly migraine-days was maintained throughout the study (100 mg, -3.9, -4.5, -4.7, and -4.5 days; 300 mg, -4.3, -4.8, -5.1, and -5.3 days; and placebo, -3.2, -3.8, -4.0, and -4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). Overall, the number of patients with a ≥50% or ≥75% reduction in migraine for each 12-week interval during the entire study was consistently numerically higher in the eptinezumab groups than in the placebo group. The proportions of patients with ≥50% reduction in migraine were similar across the eptinezumab groups. Eptinezumab was well tolerated throughout the study. Adverse events were similar across dosing periods, and there were no serious tolerability signals identified with continued dosing.ImplicationsIV eptinezumab administered every 12 weeks for up to 4 doses was associated with early and sustained migraine-preventive effects and a favorable safety profile in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895.Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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