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

Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety

“…A post hoc analysis of the ADVANCE trial data has importantly shown that the benefit of atogepant was already apparent as early as on day 1 of treatment when 10.8–14.1% of participants across the atogepant groups reported migraine versus 25.2% of participants in the placebo group, as well as in each of the first 4 weeks of treatment [ 25 ]. The early onset of a sustained therapeutic activity represents an important advantage of atogepant in comparison to many commonly prescribed preventive treatments such as β-blockers, tricyclic antidepressants, and antiseizure medications, which require titration schedules to minimize the risk of side effects and can still have delayed efficacy once the proper maintenance dose is attained [ 26 ].…”

“…Of note, the rapid onset of action has been already demonstrated with the use of CGRP-targeted monoclonal antibodies as a preventive treatment of migraine in patients with episodic migraine [ 27 – 30 ]. Although more studies are needed, the currently available evidence suggests how the rapid efficacy may be a characteristic of the drugs targeting the CGRP pathway, regardless of the administration route [ 25 ].…”

Lipidated Calcitonin Gene-Related Peptide (CGRP) Peptide Antagonists Retain CGRP Receptor Activity and Attenuate CGRP Action In Vivo

“…Two other monoclonal antibodies targeting the CGRP peptide, galcanezumab (LY2951742) and eptinezumab (ALD403) are also approved for preventative treatment of migraine. These antibody therapies are now complemented with the small molecule CGRP receptor antagonists, rimegepant (Croop et al, 2019), ubrogepant (Ailani et al, 2020) and atogepant (Schwedt et al, 2021) as approved acute treatments.…”

Role of Atogepant in the Treatment of Episodic Migraines: Clinical Perspectives and Considerations

“…On the first day of treatment, 25.2% of placebo-treated participants reported a migraine in comparison with 10.8–14.1% of participants treated with various doses of atogepant for all atogepant groups (p ≤ 0.0071). 48 Improvement in quality of life was assessed by participants’ responses to Activity Impairment in Migraine-Diaries (AIM-D) and Migraine-Specific Quality-of-Life Questionnaires (MSQ). Statistically significant improvement was reported among all treatment groups compared to placebo, expect atogepant 10 mg, which did not show a significant difference in sections of the AIM-D (p = 0.09).…”