Gepants as a New Therapeutic Option for Migraine
DOI:
https://doi.org/10.12775/QS.2026.50.67630Keywords
migraine, CGRP, gepantsAbstract
Background. Migraine is a common neurological disorder characterized by recurrent, often unilateral, throbbing headaches accompanied by other symptoms. It arises from sensory processing disorders involving activation of the trigeminal-vascular system and release of pro-inflammatory neuropeptides such as calcitonin gene-related peptide (CGRP), which is a key therapeutic target. Gepants are small-molecule CGRP receptor antagonists that block CGRP-induced pain amplification in trigeminal pathways and other related structures. Their efficacy in migraine treatment has been the focus of many recent clinical studies.
Aim. The aim of this study was to review the latest data on the therapeutic potential of gepants in acute and preventive migraine treatment, assess their safety profile, and compare their clinical utility with established therapies such as triptans and monoclonal antibodies targeting CGRP.
Material and methods. We conducted a review of the literature from 2017-2025 available in the PubMed database, using the keywords “migraine,” “CGRP,” and “gepants.”
Results. Clinical trials have shown that ubrogepant, rimegepant, and atogepant are effective in aborting acute migraine attacks, while rimegepant and zavegepant are effective in preventing migraines. Compared to currently available targeted therapies, they are less effective than triptans and comparably effective to monoclonal antibodies targeting CGRP.
Conclusions. Gepants are a safe class of medications that can be used both for prevention and for aborting migraine attacks. Although less effective than triptans, they can be used in patients who cannot be treated with them. They also have a more convenient oral form of administration compared to monoclonal antibodies, with comparable efficacy. Further research is still needed to more accurately assess the efficacy of gepants, compare them to currently approved therapies, and evaluate their potential for application in clinical practice.
References
1. Pensato, U.; Cevoli, S.; Pierangeli, G.; Cortelli, P. The Evolutionary Meaning of Migraine. Cephalalgia 2023, 43, 3331024231209303, doi:10.1177/03331024231209303.
2. Ghadiri-Sani, M. Migraine in Women: A Review. Curr. Opin. Neurol. 2025, 38, 271–276, doi:10.1097/WCO.0000000000001372.
3. Lucas, C. Migraine with Aura. Rev. Neurol. (Paris). 2021, 177, 779–784, doi:10.1016/j.neurol.2021.07.010.
4. The International Classification of Headache Disorders, 3rd Edition (Beta Version). Cephalalgia 2013, 33, 629–808, doi:10.1177/0333102413485658.
5. Iyengar, S.; Johnson, K.W.; Ossipov, M.H.; Aurora, S.K. CGRP and the Trigeminal System in Migraine. Headache 2019, 59, 659–681, doi:10.1111/head.13529.
6. Wattiez, A.-S.; Sowers, L.P.; Russo, A.F. Calcitonin Gene-Related Peptide (CGRP): Role in Migraine Pathophysiology and Therapeutic Targeting. Expert Opin. Ther. Targets 2020, 24, 91–100, doi:10.1080/14728222.2020.1724285.
7. Russo, A.F.; Hay, D.L. CGRP Physiology, Pharmacology, and Therapeutic Targets: Migraine and Beyond. Physiol. Rev. 2023, 103, 1565–1644, doi:10.1152/physrev.00059.2021.
8. Altamura, C.; Brunelli, N.; Marcosano, M.; Fofi, L.; Vernieri, F. Gepants - a Long Way to Cure: A Narrative Review. Neurol. Sci. 2022, 43, 5697–5708, doi:10.1007/s10072-022-06184-8.
9. Tepper, D. Gepants. Headache 2020, 60, 1037–1039, doi:10.1111/head.13791.
10. Younis, S.; Latysheva, N. V; Danilov, A.B.; Ashina, M. CGRP Receptor Antagonists (Gepants). Handb. Clin. Neurol. 2024, 199, 51–66, doi:10.1016/B978-0-12-823357-3.00033-1.
11. Li, D.; Abreu, J.; Tepper, S.J. A Brief Review of Gepants. Curr. Pain Headache Rep. 2023, 27, 479–488, doi:10.1007/s11916-023-01142-1.
12. Moriarty, M.A.; Barch, C.A. Gepants in Primary Care: A Targeted Approach to Acute and Preventive Treatment of Migraine. Pain Ther. 2025, 14, 1263–1278, doi:10.1007/s40122-025-00757-z.
13. Dodick, D.W.; Lipton, R.B.; Ailani, J.; Lu, K.; Finnegan, M.; Trugman, J.M.; Szegedi, A. Ubrogepant for the Treatment of Migraine. N. Engl. J. Med. 2019, 381, 2230–2241, doi:10.1056/NEJMoa1813049.
14. Lipton, R.B.; Dodick, D.W.; Ailani, J.; Lu, K.; Finnegan, M.; Szegedi, A.; Trugman, J.M. Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. JAMA 2019, 322, 1887–1898, doi:10.1001/jama.2019.16711.
15. Scott, L.J. Ubrogepant: First Approval. Drugs 2020, 80, 323–328, doi:10.1007/s40265-020-01264-5.
16. Lipton, R.B.; Croop, R.; Stock, E.G.; Stock, D.A.; Morris, B.A.; Frost, M.; Dubowchik, G.M.; Conway, C.M.; Coric, V.; Goadsby, P.J. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N. Engl. J. Med. 2019, 381, 142–149, doi:10.1056/NEJMoa1811090.
17. Croop, R.; Goadsby, P.J.; Stock, D.A.; Conway, C.M.; Forshaw, M.; Stock, E.G.; Coric, V.; Lipton, R.B. Efficacy, Safety, and Tolerability of Rimegepant Orally Disintegrating Tablet for the Acute Treatment of Migraine: A Randomised, Phase 3, Double-Blind, Placebo-Controlled Trial. Lancet (London, England) 2019, 394, 737–745, doi:10.1016/S0140-6736(19)31606-X.
18. Lipton, R.B.; Croop, R.; Stock, D.A.; Madonia, J.; Forshaw, M.; Lovegren, M.; Mosher, L.; Coric, V.; Goadsby, P.J. Safety, Tolerability, and Efficacy of Zavegepant 10 Mg Nasal Spray for the Acute Treatment of Migraine in the USA: A Phase 3, Double-Blind, Randomised, Placebo-Controlled Multicentre Trial. Lancet. Neurol. 2023, 22, 209–217, doi:10.1016/S1474-4422(22)00517-8.
19. Wiley, A.T.; Watson, J.C.; Lehmann, D.N. Acute Migraine Headache: Treatment Strategies. Am. Fam. Physician 2025, 111, 317–327.
20. Karlsson, W.K.; Ostinelli, E.G.; Zhuang, Z.A.; Kokoti, L.; Christensen, R.H.; Al-Khazali, H.M.; Deligianni, C.I.; Tomlinson, A.; Ashina, H.; Ruiz de la Torre, E.; et al. Comparative Effects of Drug Interventions for the Acute Management of Migraine Episodes in Adults: Systematic Review and Network Meta-Analysis. BMJ 2024, 386, e080107, doi:10.1136/bmj-2024-080107.
21. Yang, C.-P.; Liang, C.-S.; Chang, C.-M.; Yang, C.-C.; Shih, P.-H.; Yau, Y.-C.; Tang, K.-T.; Wang, S.-J. Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-Analysis. JAMA Netw. open 2021, 4, e2128544, doi:10.1001/jamanetworkopen.2021.28544.
22. Lipton, R.B.; Singh, R.B.H.; Revicki, D.A.; Zhao, S.; Shewale, A.R.; Lateiner, J.E.; Dodick, D.W. Functionality, Satisfaction, and Global Impression of Change with Ubrogepant for the Acute Treatment of Migraine in Triptan Insufficient Responders: A Post Hoc Analysis of the ACHIEVE I and ACHIEVE II Randomized Trials. J. Headache Pain 2022, 23, 50, doi:10.1186/s10194-022-01419-7.
23. Ashina, M.; McAllister, P.; Gaul, C.; Leyva-Rendon, A.; Ramirez, L.M.; Nalpas, C.; Thiry, A.; Abraham, L.; Fountaine, R.J.; Fullerton, T. Rimegepant for Acute Treatment of Migraine in Triptan-Unsuitable Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 4 Trial. Cephalalgia 2025, 45, 3331024251395298, doi:10.1177/03331024251395298.
24. Croop, R.; Lipton, R.B.; Kudrow, D.; Stock, D.A.; Kamen, L.; Conway, C.M.; Stock, E.G.; Coric, V.; Goadsby, P.J. Oral Rimegepant for Preventive Treatment of Migraine: A Phase 2/3, Randomised, Double-Blind, Placebo-Controlled Trial. Lancet (London, England) 2021, 397, 51–60, doi:10.1016/S0140-6736(20)32544-7.
25. Ailani, J.; Lipton, R.B.; Goadsby, P.J.; Guo, H.; Miceli, R.; Severt, L.; Finnegan, M.; Trugman, J.M.; ADVANCE Study Group Atogepant for the Preventive Treatment of Migraine. N. Engl. J. Med. 2021, 385, 695–706, doi:10.1056/NEJMoa2035908.
26. Popoff, E.; Johnston, K.; Croop, R.; Thiry, A.; Harris, L.; Powell, L.; Coric, V.; L’Italien, G.; Moren, J. 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, doi:10.1111/head.14128.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Alicja Maziarczyk, Jakub Lambach, Kacper Kutnik, Dominika Miazga, Julia Dąbrowska, Michał Białogłowski, Katarzyna Mazurek, Anna Gęborys, Maja Wojcieszak, Julia Matuszewska

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 8
Number of citations: 0