Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial

Abstract

Background: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of migraine.

Methods: In the double-blind, phase 3 ADVANCE trial, participants with 4-14 migraine days/month were randomized to atogepant 10 mg, 30 mg, 60 mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1-4, and proportion of participants with a migraine on each day during the first week.

Results: We analyzed 873 participants (n = 214 atogepant 10 mg, n = 223 atogepant 30 mg, n = 222 atogepant 60 mg, n = 214 placebo). For weeks 1-4, mean change from baseline in mean monthly migraine days ranged from -3.1 to -3.9 across atogepant doses vs -1.6 for placebo (p < 0.0001). For weeks 5-8 and 9-12, reductions in mean monthly migraine days ranged from -3.7 to -4.2 for atogepant vs -2.9 for placebo (p ≤ 0.012) and -4.2 to -4.4 for atogepant vs -3.0 for placebo (p < 0.0002), respectively. Mean change from baseline in weekly migraine days in week 1 ranged from -0.77 to -1.03 for atogepant vs -0.29 with placebo (p < 0.0001). Percentages of participants reporting a migraine on post-dose day 1 ranged from 10.8% to 14.1% for atogepant vs 25.2% with placebo (p ≤ 0.0071).

Conclusion: Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period.Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059.

Keywords: Atogepant; calcitonin gene–related peptide; efficacy; time course.

Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Todd J Schwedt serves on the Board of Directors for the American Headache Society and the International Headache Society. He has received research support from the American Migraine Foundation, Amgen, Henry Jackson Foundation, National Institutes of Health, Patient-Centered Outcomes Research Institute, and US Department of Defense. Within the past 12 months, he has received personal compensation for serving as a consultant or advisory board member for AbbVie/Allergan, Biohaven, Eli Lilly, Equinox, Lundbeck, and Novartis. He has received royalties from UpToDate. He holds stock options in Aural Analytics and Nocira.

Richard B Lipton has received research support from the National Institutes of Health, the FDA, and the National Headache Foundation. He serves as consultant, advisory board member, or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Teva, Vector, and Vedanta Research. He receives royalties from Wolff’s Headache, 8th edition (Oxford University Press, 2009), and Informa. He holds stock/options in Biohaven and Ctrl M.

Jessica Ailani has served as a consultant for AbbVie, Amgen, Axsome, Ctrl M, Eli Lilly and Company, Lundbeck, Impel, Satsuma, Theranica, Teva, and Vorso; has served as a speaker for AbbVie, Amgen, Eli Lilly and Company, Lundbeck, and Teva; has received honoraria from Medscape; and has provided editorial services to Current Pain and Headache Reports, NeurologyLive, and SELF magazine. Her institute has received clinical trial support from AbbVie, the American Migraine Foundation, Biohaven, Eli Lilly and Company, Satsuma, and Zosano.

Stephen D Silberstein is a consultant and/or advisory panel member for and has received honoraria from AbbVie, Alder Biopharmaceuticals, Amgen, Avanir, eNeura, electroCore Medical, Labrys Biologics, Medscape, Medtronic, Neuralieve, NINDS, Pfizer, and Teva. His employer receives research support from AbbVie, Amgen, Cumberland Pharmaceuticals, electroCore Medical, Labrys Biologics, Eli Lilly, Mars, and Troy Healthcare.

Cristina Tassorelli has participated in advisory boards for AbbVie, electroCore, Eli Lilly, Novartis, and Teva. She has lectured at symposia sponsored by AbbVie, Eli Lilly, Novartis, and Teva. She is principal investigator or collaborator in clinical trials sponsored by Alder, Eli Lilly, IBSA, Novartis, and Teva. She has received research grants from the European Commission, the Italian Ministry of Health, the Italian Ministry of University, the Migraine Research Foundation, and the Italian Multiple Sclerosis Foundation.

Hua Guo, Kaifeng Lu, Brett Dabruzzo, Rosa Miceli, Lawrence Severt, Michelle Finnegan and Joel M Trugman are employees of AbbVie and may hold AbbVie stock.

Figures

Figure 1.

Change from baseline monthly migraine days during the treatment period (mITT population).*P<0.05; **P<0.01; ***P<0.001. LS, least squares; mITT, modified intent-to-treat; MMD, monthly migraine day; SE, standard error.

Figure 2.

Change from baseline in weekly migraine days during the first month of treatment (mITT population).*P<0.05; **P<0.01; ***P<0.001. LS, least squares; mITT, modified intent-to-treat; SE, standard error.

Figure 3.

Proportion of participants with a migraine each day during the first week of treatmenta (mITT population). *P<0.05; **P<0.01; ***P<0.001. mITT, modified intent-to-treat. aDay 0 excluded, as migraine attacks occurring prior to study drug administration were included.