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Clinical Trial
. 2025 Jan 28;104(2):e210212.
doi: 10.1212/WNL.0000000000210212. Epub 2024 Dec 23.

Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials

Richard B Lipton  1 , Pranav Gandhi  2 , Cristina Tassorelli  3   4 , Uwe Reuter  5 , Andrea M Harriott  6 , Dagny Holle-Lee  7   8 , Christopher H Gottschalk  9 , Brian Neel  10 , Yingyi Liu  11 , Hua Guo  2 , Jonathan Stokes  2 , Krisztian Nagy  12 , Brett Dabruzzo  2 , Jonathan H Smith  11
Affiliations
Clinical Trial

Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials

Richard B Lipton et al. Neurology. .

Abstract

Background and objectives: Three phase 3 trials demonstrated the efficacy and safety of atogepant in episodic migraine (EM) and chronic migraine (CM) across 12-week treatment periods. This analysis evaluates improvements in efficacy and functional outcomes in the first 4 weeks of treatment with the oral calcitonin gene-related peptide receptor antagonist, atogepant, for the preventive treatment of migraine.

Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials. ADVANCE and ELEVATE included participants aged 18-80 years with >1 year history of EM and 4-14 monthly migraine days (MMDs). ELEVATE required previous treatment failures to 2-4 classes of oral preventives. PROGRESS included participants aged 18-80 years with >1 year history of CM, ≥15 monthly headache days, and ≥8 MMDs. This analysis reports the atogepant 60 mg once daily (QD) and placebo treatment arms. Outcomes included efficacy endpoints (reporting a migraine day on day 1, change from baseline in weekly migraine days [WMDs] at weeks 1-4, and in MMDs in the first 4 weeks) and functional endpoints evaluated by the Activity Impairment in Migraine-Diary (AIM-D) at weeks 1-4 and the European Quality-of-Life 5-Dimension 5-Level (EQ-5D-5L) at weeks 1-2 and 4.

Results: The modified intent-to-treat population included the ADVANCE (atogepant, n = 222; placebo, n = 214), ELEVATE (atogepant, n = 151; placebo, n = 154), and PROGRESS (atogepant, n = 256; placebo, n = 246) studies. Atogepant-treated participants had greater reductions in the proportion of participants with a migraine day on day 1. The odds ratio compared with placebo was 0.39 (95% CI 0.23-0.67; p = 0.0006) in ADVANCE, 0.53 (95% CI 0.29-0.94, p = 0.031) in ELEVATE, and 0.63 (95% CI 0.43-0.93, p = 0.021) in PROGRESS. Atogepant treatment reduced WMDs at weeks 1-4 and MMDs in the first 4 weeks, and improved AIM-D and EQ-5D-5L at all assessed timepoints for weeks 1-4 compared with placebo.

Discussions: Atogepant 60 mg QD demonstrated superiority to placebo in efficacy and functional measures in the first 4 weeks of treatment across 3 preventive studies, 2 in EM and 1 in CM.

Trial registration: ClinicalTrials.gov NCT03777059; NCT04740827; NCT03855137. Submitted: 12/13/2018; 02/02/2021; 02/25/2019. First patient enrolled: 12/14/2018; 03/05/2021; 03/11/2019 clinicaltrials.gov/ct2/show/NCT03777059. clinicaltrials.gov/ct2/show/NCT04740827 clinicaltrials.gov/ct2/show/NCT03855137.

Classification of evidence: This study provides Class II evidence that atogepant 60 mg QD reduces migraine frequency and improves functional outcomes within 4 weeks of initiation in patients with EM and patients with CM.

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Conflict of interest statement

R.B. Lipton has received research support from the NIH, the FDA, and the National Headache Foundation; serves as a consultant for, advisory board member of, 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; receives royalties from Wolff's Headache, 8th edition (Oxford University Press, 2009), and Informa; and holds stock/options in Axon, Biohaven, CoolTech, and Manistee. C. Tassorelli has participated in advisory boards for AbbVie, Dompé, Eli Lilly, Ipsen, Lundbeck, Medscape, Pfizer, and Teva; has lectured at symposia sponsored by AbbVie, Eli Lilly, Lundbeck, Pfizer, and Teva; is principal investigator or collaborator in clinical trials sponsored by AbbVie, Eli Lilly, Ipsen, Lundbeck, Pfizer, and Teva; and 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. U. Reuter has served on advisory boards for Amgen, Allergan, AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva; has received institutional honoraria for lectures from Amgen, Allergan, AbbVie, Eli Lilly, Lundbeck, Novartis, electroCore, Medscape, StreaMedUp, Springer, and Teva; received institutional honoraria for consulting services from Lundbeck, Pfizer, and AbbVie; received research funding from Novartis (CHERUB01) and the German Federal Ministry of Education and Research; and is an associate editor of the Journal of Headache and Pain. A. Harriott has received personal compensation for serving as an officer or member of the Board of Directors for Headache Cooperative of New England. The institution of Dr. Harriott has received research support from electroCore. She has a non-compensated relationship as an author with AbbVie that is relevant to AAN interests or activities. D. Holle-Lee received honoraria for consulting from AbbVie/Allergan, Amgen, Eli Lilly, Novartis, Teva, Lundbeck, Hormosan, and Zuellig Pharma. C.H. Gottschalk has been a paid consultant for Alder/Lundbeck, Biohaven, Amgen/Novartis, Theranica, Axsome, Upsher Smith, Spherix Global Insights, and Vorso; has been a past member of speaker bureaus for Amgen/Novartis, Allergan/AbbVie, Biohaven, Lilly, Theranica, and Upsher Smith; served as an associate editor of Headache until 2020; and is a board member of the Headache Cooperative of New England (HCNE). P. Gandhi, B. Neel, Y. Liu, H. Guo, J. Stokes, K. Nagy, B. Dabruzzo, and J.H. Smith are all employees of AbbVie Inc. and may hold AbbVie stock. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Participant Disposition for ADVANCE (A), ELEVATE (B), and PROGRESS (C)
Figure 1A from New England Journal of Medicine, Jessica Ailani, Richard B. Lipton, Peter J Goadsby, et al. Atogepant for the Preventive Treatment of Migraine, Volume No. 385, Page No. 695–706, Copyright © 2021 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Figure 1B reprinted from Lancet Neurology, 23(4), Tassorelli C, Nagy K, Pozo-Rosich P, et al., “Atogepant for the preventive treatment of episodic migraine in adults with prior inadequate responses to conventional oral preventive treatment (ELEVATE): a randomised, double-blind, placebo-controlled, parallel-group phase 3b trial,” 382–392, Copyright (2024); with permission from Elsevier. Figure 1C used with permission from Elsevier Science & Technology Journals, from Pozo-Rosich P et al., Lancet; 2023; 402:775-785. doi:10.1016/S0140-6736(23)01049-8; permission conveyed through Copyright Clearance Center, Inc.
Figure 2
Figure 2. Proportion of Participants With a Migraine Day on Day 1 for ADVANCE (A), ELEVATE (B), and PROGRESS (C) (Modified Intent-to-Treat Population)
The results from ADVANCE have been previously published and are included for reference. n = number of participants with a migraine day on day 1 post dose; N = number of participants assessed at timepoint.
Figure 3
Figure 3. Change From Baseline in Weekly Migraine Days at Weeks 1, 2, 3, and 4 for ADVANCE (A), ELEVATE (B), and PROGRESS (C) (Modified Intent-to-Treat Population)
The results from ADVANCE have been previously published and are included for reference. n = number of participants assessed at timepoint; N = number of participants randomized to study treatment.
Figure 4
Figure 4. Change From Baseline in Mean Monthly Migraine Days in the First 4 Weeks for ADVANCE (A), ELEVATE (B), and PROGRESS (C) (Modified Intent-to-Treat Population)
The results from ADVANCE have been previously published and are included for reference. n = number of participants assessed at timepoint; N = number of participants randomized to study treatment.
Figure 5
Figure 5. Change From Baseline in the Performance of Daily Activities Domain of the AIM-D at Weeks 1, 2, 3, and 4 for ADVANCE (A), ELEVATE (B), and PROGRESS (C) (Modified Intent-to-Treat Population)
n = number of participants assessed at timepoint; N = number of participants randomized to study treatment.
Figure 6
Figure 6. Change From Baseline in the Physical Impairment Domain of AIM-D at Weeks 1, 2, 3, and 4 for ADVANCE (A), ELEVATE (B), and PROGRESS (C) (Modified Intent-to-Treat Population)
n = number of participants assessed at timepoint; N = number of participants randomized to study treatment.
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References

    1. Safiri S, Pourfathi H, Eagan A, et al. . Global, regional, and national burden of migraine in 204 countries and territories, 1990 to 2019. Pain. 2022;163(2):e293-e309. doi:10.1097/j.pain.0000000000002275 - DOI - PubMed
    1. Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z, Lifting The Burden the Global Campaign against Headache. Migraine remains second among the world's causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020;21(1):137. doi:10.1186/s10194-020-01208-0 - DOI - PMC - PubMed
    1. GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23(4):344-381. doi:10.1016/s1474-4422(24)00038-3 - DOI - PMC - PubMed
    1. Buse DC, Fanning KM, Reed ML, et al. . Life with migraine: effects on relationships, career, and finances from the chronic migraine epidemiology and outcomes (CaMEO) study. Headache. 2019;59(8):1286-1299. doi:10.1111/head.13613 - DOI - PMC - PubMed
    1. Buse DC, Rupnow MFT, Lipton RB. Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc. 2009;84(5):422-435. doi:10.1016/S0025-6196(11)60561-2 - DOI - PMC - PubMed

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