Article Data

  • Views 248
  • Dowloads 46

Reviews

Open Access

Efficacy and safety of gepants in migraine management: a narrative review focusing on atogepant and rimegepant

  • Audrey Gautier1
  • Thomas Gicquel2,3
  • Marion Mercerolle4
  • Brendan Le Daré2,4,*,

1Rennes University, 35000 Rennes, France

2INSERM, INRAE, Institut NuMeCan (Nutrition, Metabolism and Cancer), Rennes University, 35033 Rennes, France

3Biological and Forensic Toxicology Laboratory, Rennes University Hospital, 35033 Rennes, France

4Pharmacy Department, Rennes University Hospital, 35033 Rennes, France

DOI: 10.22514/jofph.2026.046 Vol.40,Issue 4,July 2026 pp.1-8

Submitted: 26 December 2025 Accepted: 30 January 2026

Published: 12 July 2026

*Corresponding Author(s): Brendan Le Daré E-mail: brendan.le.dare@chu-rennes.fr

Abstract

Gepants, oral antagonists of the calcitonin gene-related peptide (CGRP) receptor, represent a new therapeutic class in migraine management. This review aims to assess the efficacy and safety profile of the two gepants currently available in France: atogepant and rimegepant. A review of the literature was conducted in July 2024 using the PubMed, Cochrane Library, and Web of Science databases. Randomized controlled trials evaluating the efficacy and/or safety of atogepant and rimegepant in adult patients with migraine were included. Sixteen randomized controlled trials were selected (nine evaluating atogepant and seven evaluating rimegepant). In migraine prevention, atogepant significantly reduced the mean number of monthly migraine days (−0.7 to −2.4 days vs. placebo), with an improvement in quality-of-life scores (Migraine-Specific Quality of Life questionnaire—Role Function-Restrictive domain (MSQ-RFR):+9.9 to +10.8 points). Rimegepant, administered every other day, achieved a smaller reduction (−0.8 days/month) but was comparable to that observed with some anti-CGRP monoclonal antibodies. In acute treatment, a single dose of rimegepant 75 mg provided complete pain relief at 2 hours in 31–33% of patients versus 15% with placebo. Adverse events, mainly gastrointestinal (constipation and nausea), were generally mild to moderate, with no signal of hepatic or cardiovascular toxicity. Gepants represent a major therapeutic advance combining clinically meaningful efficacy with a favorable safety profile. Atogepant appears particularly promising for migraine prevention, whereas rimegepant offers an effective and well-tolerated option for acute treatment. Their use in clinical practice remains limited in France due to high cost and restricted reimbursement. Further real-world and long-term studies are needed to better define their place within current migraine management strategies.


Keywords

Migraine; Gepants; Atogepant; Rimegepant; CGRP; Efficacy; Safety


Cite and Share

Audrey Gautier,Thomas Gicquel,Marion Mercerolle,Brendan Le Daré. Efficacy and safety of gepants in migraine management: a narrative review focusing on atogepant and rimegepant. Journal of Oral & Facial Pain and Headache. 2026. 40(4);1-8.

References

[1] Steiner TJ, Stovner LJ. Global epidemiology of migraine and its implications for public health and health policy. Nature Reviews Neurology. 2023; 19: 109–117.

[2] Caronna E, Gallardo VJ, Alpuente A, Torres-Ferrus M, Pozo-Rosich P. Epidemiology, work and economic impact of migraine in a large hospital cohort: time to raise awareness and promote sustainability. Journal of Neurology. 2022; 269: 1456–1462.

[3] Eltrafi A, Shrestha S, Ahmed A, Mistry H, Paudyal V, Khanal S. Economic burden of chronic migraine in OECD countries: a systematic review. Health Economics Review. 2023; 13: 43. Erratum in: Health Economics Review. 2023; 13: 49.

[4] Dodick DW. A phase-by-phase review of migraine pathophysiology. Headache. 2018; 58: 4–16.

[5] French Ministry of Health. VYDURA 75 mg, orally disintegrating tablet—drug information sheet. Public Drug Database. 2022. Available at: https://base-donnees-publique.medicaments.gouv.fr/extrait.php?specid=65899221 (Accessed: 18 January 2025).

[6] French Ministry of Health. AQUIPTA 60 mg, film-coated tablet—drug information sheet. Public Drug Database. 2023. Available at: https://base-donnees-publique.medicaments.gouv.fr/extrait.php?specid=69498539 (Accessed: 18 January 2025).

[7] Moisset X, Demarquay G, de Gaalon S, Roos C, Donnet A, Giraud P, et al. Migraine treatment: position paper of the French Headache Society. Revista de Neurología. 2024; 180: 1087–1099.

[8] Siddaway AP, Wood AM, Hedges LV. How to do a systematic review: a best practice guide for conducting and reporting narrative reviews, meta-analyses, and meta-syntheses. Annual Review of Psychology. 2019; 70: 747–770.

[9] Tassorelli C, Nagy K, Pozo-Rosich P, Lanteri-Minet M, Sacco S, Nežádal T, et al. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. The Lancet Neurology. 2024; 23: 382–392.

[10] Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. The Lancet Neurology. 2020; 19: 727–737.

[11] Goadsby PJ, Friedman DI, Holle-Lee D, Demarquay G, Ashina S, Sakai F, et al. Efficacy of atogepant in chronic migraine with and without acute medication overuse in the randomized, double-blind, phase 3 PROGRESS trial. Neurology. 2024; 103: e209584.

[12] Lipton RB, Nahas SJ, Pozo-Rosich P, Bilchik T, McAllister P, Finnegan M, et al. Sustained response to atogepant in episodic migraine: post hoc analyses of a 12-week randomized trial and a 52-week long-term safety trial. The Journal of Headache and Pain. 2024; 25: 83.

[13] Lipton RB, Pozo-Rosich P, Blumenfeld AM, Li Y, Severt L, Stokes JT, et al. Effect of atogepant for preventive migraine treatment on patient-reported outcomes in the randomized, double-blind, phase 3 ADVANCE trial. Neurology. 2023; 100: e764–e777.

[14] Ashina M, Tepper SJ, Reuter U, Blumenfeld AM, Hutchinson S, Xia J, et al. Once-daily oral atogepant for the long-term preventive treatment of migraine: findings from a multicenter, randomized, open-label, phase 3 trial. Headache. 2023; 63: 79–88.

[15] Schwedt TJ, Lipton RB, Ailani J, Silberstein SD, Tassorelli C, Guo H, et al. Time course of efficacy of atogepant for the preventive treatment of migraine: results from the randomized, double-blind ADVANCE trial. Cephalalgia. 2022; 42: 3–11.

[16] Lipton RB, Pozo-Rosich P, Blumenfeld AM, Dodick DW, McAllister P, Li Y, et al. Rates of response to atogepant for migraine prophylaxis among adults: a secondary analysis of a randomized clinical trial. JAMA Network Open. 2022; 5: e2215499.

[17] Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, et al. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023; 402: 775–785.

[18] Croop R, Lipton RB, Kudrow D, Stock DA, Kamen L, Conway CM, et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. The Lancet. 2021; 397: 51–60.

[19] Schwedt T, Oakes T, Martinez J, Vargas B, Pandey H, Pearlman E, et al. Comparing the efficacy and safety of galcanezumab versus rimegepant for prevention of episodic migraine: results from a randomized, controlled clinical trial. Neurology and Therapy. 2024; 13: 85–105.

[20] Croop R, Goadsby P, Stock D, Conway C, Forshaw M, Stock E, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. The Lancet. 2019; 394: 737–745.

[21] Yu S, Guo A, Wang Z, Liu J, Tan G, Yang Q, et al. Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial. The Journal of Headache and Pain. 2024; 25: 57.

[22] Marcus R, Goadsby P, Dodick D, Stock D, Manos G, Fischer T. BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia. 2014; 34: 114–125.

[23] Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. The New England Journal of Medicine. 2019; 381: 142–149.

[24] Yu S, Kim BK, Guo A, Kim MH, Zhang M, Wang Z, et al. Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial. The Lancet Neurology. 2023; 22: 476–484.

[25] Lattanzi S, Trinka E, Altamura C, Del Giovane C, Silvestrini M, Brigo F, et al. Atogepant for the prevention of episodic migraine in adults: a systematic review and meta-analysis of efficacy and safety. Neurology and Therapy. 2022; 11: 1235–1252.

[26] Popoff E, Johnston K, Croop R, Thiry A, Harris L, Powell L, et al. Matching-adjusted indirect comparisons of oral rimegepant versus placebo, erenumab, and galcanezumab examining monthly migraine days and health-related quality of life in the treatment of migraine. Headache. 2021; 61: 906–915.

[27] Wang Q, Wang S, Zhu Y, Lin F. Clinical efficacy and safety of rimegepant in the treatment of migraine: a meta-analysis of randomized controlled trials. Frontiers in Neurology. 2023; 14: 1205778.

[28] Liang Q, Liao X, Wu H, Huang Y, Liang T, Li H. Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration’s adverse event reporting system databases. Frontiers in Pharmacology. 2024; 15: 1431562.

[29] Dodick DW, Goadsby PJ, Schwedt TJ, Lipton RB, Liu C, Lu K, et al. Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. The Lancet. 2023; 402: 2307–2316.

[30] Deng X, Zhou L, Liang C, Shang X, Hui X, Liu W, et al. Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials. The Journal of Headache and Pain. 2024; 25: 16.

[31] Haute Autorité de Santé. AQUIPTA (atogepant)—Migraine. 2024. Available at: https://www.has-sante.fr/jcms/p_3483609/fr/aquipta-atogepant-migraine (Accessed: 18 January 2025).

[32] Ailani J, Lewis M, Dai F, Jenkins A, Cirillo J, Hygge Blakeman K, et al. Evaluation of rimegepant utilization patterns and patient characteristics among new users: a United States administrative claims-based study. Current Medical Research and Opinion. 2024; 40: 1913–1920.

[33] Puledda F, de Boer I, Messina R, Garcia-Azorin D, Portes Souza MN, Al-Karagholi MAM, et al. Worldwide availability of medications for migraine and tension-type headache: a survey of the International Headache Society. Cephalalgia. 2024; 44: 03331024241297688.

[34] Lee MJ, Al-Karagholi MAM, Reuter U. New migraine prophylactic drugs: current evidence and practical suggestions for non-responders to prior therapy. Cephalalgia. 2023; 43: 3331024221146315.


Submission Turnaround Time

Top