Atogepant in the prevention of migraine

There has been the discovery that migraine attacks may be related to the provocation action of calcitonin gene-related peptide (CGRP) (1).

Atogepant is a CGRP receptor antagonist (gepant) that is used in the prevention of migraine:

• is an orally administered small molecule that has a much shorter half-life than CGRP monoclonal antibodies and may have the advantage of being more convenient and acceptable for some specific patients
• in terms of dosing frequency, the small molecule atogepant needs to be taken orally every day
• with regard to treatment-related adverse events, gastrointestinal symptoms such as nausea and constipation are the most common (1)
• has shown good efficacy and safety in the prophylactic treatment of migraine
• daily use of oral atogepant 60 mg for the preventive treatment of migraine during a 1‐year, open‐label trial was safe and well tolerated (2)
• in the PROGRESS trial, preventive treatment with atogepant in participants with chronic migraine and acute medication overuse, without specific guidance for acute medication withdrawal, was associated with greater improvements in efficacy outcomes compared with placebo (3)

NICE state (4):

• Atogepant is recommended as an option for preventing migraine in adults who have at least 4 migraine days per month, only if at least 3 preventive medicines have failed
• Stop atogepant after 12 weeks if the frequency of migraines does not reduce by
  • at least 50% in episodic migraine (defined as fewer than 15 headache days per month)
  • at least 30% in chronic migraine (defined as 15 or more headache days per month, with at least 8 of those having features of migraine).

Reference:

1. Tao X, Yan Z, Meng J, Wang W, Dai Q, Zhou Q, Wang Z, Wang Z. The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials. J Headache Pain. 2022 Jan 29;23(1):19.
2. Ashina M, Tepper SJ, Reuter U, Blumenfeld AM, Hutchinson S, Xia J, Miceli R, Severt L, Finnegan M, Trugman JM. Once-daily oral atogepant for the long-term preventive treatment of migraine: Findings from a multicenter, randomized, open-label, phase 3 trial. Headache. 2023 Jan;63(1):79-88.
3. Goadsby PJ, Friedman DI, Holle-Lee D, Demarquay G, Ashina S, Sakai F, Neel B, Gandhi P, Dabruzzo B, Smith JH, Liu Y, Trugman JM. Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial. Neurology. 2024 Jul 23;103(2):e209584.
4. NICE (May 2024). Atogepant for preventing migraine