NEUROLOGY
CONFERENCE UPDATE

Atogepant demonstrates superior efficacy and tolerability vs. topiramate in migraine prevention: Results from the head-to-head TEMPLE trial

28 Jul 2026

Share

STUDY DESIGN

Migraine is a highly prevalent neurological disorder characterized by recurrent headache attacks, frequently accompanied by nausea and increased sensitivity to light, sound, or movement.1 Atogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, and topiramate are established preventive treatment options for migraine.1 Given that head-to-head trials are the gold standard for comparative treatment evaluation, the TEMPLE trial was conducted to evaluate the safety, tolerability, and efficacy of atogepant vs. the highest tolerated dose of topiramate in adults with migraine.1

TEMPLE was a phase 3b, multicenter, randomized, double-blind, double-dummy, parallel-group, active-controlled trial with an open-label atogepant extension.1 Participants were randomized to receive either atogepant 60mg once daily (QD) or topiramate at the highest tolerated dose (50mg, 75mg, or 100mg QD).1 Eligible participants were aged 18-80 years with a documented history of migraine for ≥12 months prior to screening and ≥4 migraine days per month during the screening or baseline period.1 Participants had no prior exposure to topiramate or atogepant.1 The study consisted of a 6-week up-titration phase followed by an 18-week maintenance phase during the double-blind treatment period.1

The safety population included all participants who received ≥1 dose of study treatment during the double-blind treatment period (n=540).1 The modified intent-to-treat (mITT) population (n=527) included randomized participants who received ≥1 dose of study treatment, had evaluable baseline data, and had ≥1 evaluable post-baseline 4-week period within 24 weeks after the first dose.1 Among the mITT population, 372 participants completed the full 24-week double-blind treatment period without premature discontinuation of study drug and with treatment duration of ≥165 days.1 Baseline characteristics were generally well-balanced between treatment groups.1

The primary endpoint was the incidence of treatment discontinuation due to treatment-emergent adverse events (TEAEs) during the 24-week double-blind treatment period among the safety population.1 Secondary endpoints evaluated the proportion of patients who achieved ≥50% reduction in mean monthly migraine days (MMDs) and change from baseline in mean MMDs during months 4-6 of the double-blind treatment period in the mITT and double-blind treatment completers populations.1

FINDINGS

Primary endpoint:
  • The primary endpoint was the incidence of treatment discontinuation due to TEAEs during the 24-week double-blind treatment period among the safety population1
  • Atogepant demonstrated superior tolerability vs. topiramate, with significantly fewer participants discontinuing treatment due to TEAEs over 24 weeks (12.1% vs. 29.6%; relative risk [RR]=0.41; 95% CI: 0.28-0.59; p<0.0001)1
Secondary endpoints:
  • Secondary endpoints evaluated proportion of patients who achieved ≥50% reduction in mean MMDs and change from baseline in mean MMDs during months 4-6 of the double-blind treatment period in the mITT and double-blind treatment completers populations1
  • Achievement of ≥50% reduction in mean MMDs
    • During months 4-6, a higher proportion of participants receiving atogepant achieved a ≥50% reduction in mean MMDs vs. those receiving topiramate in the mITT population (64.1% vs. 39.3%; RR=1.6; 95% CI: 1.4-2.0; p<0.0001)1
    • Similar findings were observed among double-blind treatment completers, with 73.7% of atogepant-treated participants achieving ≥50% reduction in mean MMDs vs. 48.5% with topiramate (RR=1.5; 95% CI: 1.3-1.8; nominal p=0.0002)1
  • Change in mean MMDs from baseline
    • Atogepant demonstrated greater reductions in mean MMDs from baseline during months 4-6 vs. topiramate in both the mITT population (-6.3 vs. -4.5 days; 95% CI: -2.5 to -1.0; p<0.0001) and double-blind treatment completers population (-6.6 vs. -5.0 days; 95% CI: -2.5 to -0.8; nominal p=0.0002)1
Safety:
  • The adverse events profile of atogepant was generally consistent with its established safety profile, with no new safety signals identified1
  • Atogepant was generally safe and well-tolerated, with a lower incidence of TEAEs (76.9% vs. 88.8%) and TEAEs related to study treatment (56.0% vs. 77.9%) over 24 weeks compared with topiramate, while serious TEAEs were infrequent in both treatment groups (2.2% vs. 1.1%)1
  • The most commonly reported TEAEs with atogepant included nausea (19.8%), fatigue (15.4%), decreased appetite (12.5%), nasopharyngitis (11.0%), and constipation (9.9%)1

 

“Atogepant demonstrated superior tolerability with significantly fewer treatment discontinuations due to adverse events across 24 weeks compared with topiramate”

Dr. Uwe Reuter
University Hospital Greifswald, Germany

​

References

  1. Reuter U, et al. Tolerability, safety, and efficacy of atogepant versus topiramate in adult participants with migraine: Results from the Head-to-Head TEMPLE Trial. Presented at the American Academy of Neurology (AAN) Annual Meeting 2026; April 18-22, 2026.

MIGRAINE
MEAN MONTHLY MIGRAINE DAYS
TREATMENT DISCONTINUATION

Login

Get access to our exclusive articles.

Related articles