Three Phase 3, Placebo-Controlled Trials Show Rapid Benefits of Oral Atogepant for Migraine Prevention
26 Dec, 2024 | 12:17h | UTCBackground: Preventive therapies for migraine often require long titration and may take weeks to achieve their full effect. This analysis integrates data from three randomized, placebo-controlled Phase 3 trials (ADVANCE, ELEVATE, PROGRESS) assessing atogepant 60 mg once daily (QD) over 12 weeks, focusing on the first four weeks. A key point is that atogepant was compared only to placebo, not to other well-established migraine preventives.
Objective: To determine whether atogepant provides early efficacy in reducing migraine frequency and improving functional outcomes within the initial weeks of therapy, for both episodic and chronic migraine.
Methods: All three studies enrolled participants aged 18–80 years with a ≥1-year history of migraine. ADVANCE and ELEVATE focused on episodic migraine (EM; 4–14 monthly migraine days), while PROGRESS studied chronic migraine (CM; ≥15 monthly headache days, ≥8 of which met migraine criteria). In ELEVATE, participants had previously failed 2–4 classes of oral migraine preventives. Throughout each trial, patients recorded daily migraine-related data and completed validated functional assessments (AIM-D and EQ-5D-5L). For this pooled analysis, only the atogepant 60 mg QD and placebo arms were examined.
Results: Atogepant recipients had a significantly lower proportion of patients with a migraine day on day 1 in all three trials, suggesting a rapid onset of benefit. Reductions in weekly migraine days (WMDs) emerged as early as week 1 and remained consistently greater than placebo over the first four weeks. Functional measures improved within this same timeframe, with patients on atogepant reporting reductions in activity impairment and enhanced self-rated health. These positive findings were observed in EM (with or without prior prophylaxis failures) and in CM populations.
Conclusions: Atogepant 60 mg QD was linked to early and significant reductions in migraine days, as well as enhancements in physical functioning and daily activities, across three placebo-controlled studies. The data suggest that atogepant may offer clinically meaningful, rapid-onset prophylactic benefits.
Implications for Practice: Clinicians may consider atogepant for patients seeking a preventive migraine therapy that demonstrates a potentially faster impact on symptom frequency and daily functioning. However, direct comparisons with established active treatments are lacking, and appropriate caution in interpreting the early onset of benefit is recommended.
Study Strengths and Limitations: Major strengths include robust, double-blind methodologies and consistent findings across diverse migraine populations. A key limitation is the exclusive use of placebo as the comparator, so the relative advantage over standard preventives remains unknown. The predominantly female and White study cohorts also restrict generalizability.
Future Research: Further investigations should evaluate atogepant in direct comparisons with existing active migraine preventives, examine long-term outcomes, and recruit more diverse populations. Such efforts could better define the therapy’s place in routine migraine care.
Reference: Lipton RB, et al. Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials. Neurology. 2025;104(2). DOI: https://doi.org/10.1212/WNL.0000000000210212