Indirect Comparison Analysis of Head-to-Head Migraine Trials Suggests Early Efficacy Advantage With Atogepant Over Erenumab

A recent indirect treatment comparison presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18–22 in Chicago, Illinois, indicated that treatment with atogepant (Qulipta; AbbVie) was linked to a greater likelihood of achieving a clinically meaningful reduction in monthly migraine days (MMDs) in the first month vs erenumab (Aimovig; Amgen), suggesting a potentially earlier treatment.¹

Findings showed that atogepant and erenumab had similar safety and tolerability profiles over 24 weeks in adults with migraine. At 1 month in the overall population, atogepant was associated with significantly greater odds of achieving a 50% or greater reduction in MMDs compared with erenumab (odds ratio, 1.73; 95% Cl, 1.07 to 2.82; P = .03). Notably, the change from baseline in MMDs was not significantly different between groups (mean difference, −0.69; 95% CI, −1.69 to 0.31; P = .18).

Presented by Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, this indirect treatment comparison study evaluated the efficacy, safety, and tolerability of atogepant and erenumab, two FDA-approved treatments, in adults with migraine. The analysis utilized data from the phase 3b TEMPLE trial (NCT05748483) of atogepant 60 mg once daily and the phase 4 HER-MES trial (NCT03828539) of erenumab 70 mg or 140 mg once monthly, each of which included comparisons with topiramate (Topamax). In both studies, the primary end point was the proportion of participants who discontinued treatment because of adverse events (AEs).

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For this analysis, tolerability and safety were evaluated over a 24-week period, including assessments of AEs, AEs leading to treatment discontinuation, and serious AEs. Efficacy was analyzed at 1 month and 4 through 6 months in the overall population, as well as in subgroups stratified by baseline MMDs. Key efficacy end points included the likelihood of achieving a 50% or greater reduction in mean MMDs and the change from baseline in mean MMDs.

Among participants with 8 to 14 baseline MMDs, researchers reported that atogepant demonstrated a significantly greater reduction in MMDs at 1 month relative to erenumab (mean difference, −1.50; 95% CI, −2.69 to −0.31; P = .013). Across other baseline MMD subgroups, authors also noted that efficacy outcomes were generally comparable between treatments at all evaluated time points.

Erenumab was the first calcitonin gene–related peptide (CGRP) inhibitor in its class to receive approval in May 2018, based on results from 3 clinical trials evaluating a once-monthly self-administered injectable formulation.² Atogepant, another CGRP-targeting therapy, was initially approved in September 2021 for the preventive treatment of episodic migraine, with its indication subsequently expanded to include chronic migraine in April 2023.³

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REFERENCES
1. Tepper S, Gandhi P, Ubamadu I, et al. Comparative Efficacy, Safety, and Tolerability of Atogepant and Erenumab: Indirect Treatment Comparison of the TEMPLE and HER-MES Head-to-head Trials. Presented at: 2026 AAN Annual Meeting; April 18-22; Chicago, Illinois.
2. FDA Approves Aimovig™ (erenumab-aooe), A Novel Treatment Developed Specifically For Migraine Prevention. News release. Amgen. May 17, 2018. Accessed April 17, 2026. https://www.amgen.com/newsroom/press-releases/2018/05/fda-approves-aimovig-erenumabaooe-a-novel-treatment-developed-specifically-for-migraine-prevention
3. FDA Approves QULIPTA™ (atogepant), the First and Only Oral CGRP Receptor Antagonist Specifically Developed for the Preventive Treatment of Migraine. News release. AbbVie. September 28, 2021. Accessed April 17, 2026. https://news.abbvie.com/news/press-releases/fda-approves-qulipta-atogepant-first-and-only-oral-cgrp-receptor-antagonist-specifically-developed-for-preventive-treatment-migraine.htm?view_id=1531