Atogepant beat topiramate on tolerability and migraine days head-to-head
TEMPLE, an AbbVie-funded phase 3b trial, is the first direct test of the CGRP blocker atogepant against topiramate — a long-used preventive many patients cannot tolerate.
| Group | Value (%) |
|---|---|
| Atogepant 60 mg | 12 |
| Topiramate | 30 |
The newer, migraine-specific preventive atogepant was easier to stay on than the decades-old standby topiramate, and cut migraine days more often, in the first trial to pit the two directly against each other [s1]. The result is not surprising — topiramate's poor tolerability is well known — but a head-to-head trial is the kind of evidence that has been missing, and it comes from the maker of the newer drug.
Oral calcitonin gene-related peptide (CGRP) receptor antagonists such as atogepant have been approved to prevent migraine but had not been compared directly with conventional oral preventives [s1]. Topiramate is widely used but its use is often limited by poor tolerability [s1]. TEMPLE was built to supply that missing comparison.
What the trial did
TEMPLE was a phase 3b, randomised, double-dummy, active-controlled trial with a 24-week double-blind period followed by a 52-week open-label period, run across 12 countries [s1]. Participants had a history of migraine with at least four migraine days per month [s1]. They were randomly assigned 1:1 to atogepant 60 mg once daily or to topiramate at the highest tolerated dose of 50, 75, or 100 mg per day [s1]. The primary endpoint was tolerability, measured as treatment discontinuation due to treatment-emergent adverse events during the double-blind period [s1]. Between Oct 7, 2023, and April 28, 2025, 730 participants were screened, 545 were randomly assigned, and 540 — 479 (89%) female, 61 (11%) male, and 517 (96%) White — made up the safety population, with 273 on atogepant and 267 on topiramate [s1]. The trial was registered before recruitment [s2].
What it found
On the primary tolerability endpoint, discontinuation because of adverse events over 24 weeks was lower with atogepant: 33 (12%) of 273 patients stopped, versus 79 (30%) of 267 on topiramate — a relative risk of 0.4 (95% CI 0.3 to 0.6, p<0.0001) [s1]. Treatment-related adverse events followed the same pattern, reported by 153 (56%) of 273 on atogepant and 208 (78%) of 267 on topiramate [s1]. Serious treatment-emergent adverse events were uncommon in both arms — six on atogepant and three on topiramate — with a single event, an anaphylactic reaction in the atogepant group, considered related to the study drug; no deaths occurred [s1]. Topiramate was dosed to the highest level each patient could tolerate, up to 100 mg per day, so the discontinuation gap reflects a comparison against the drug used as it is in practice rather than against a deliberately low, better-tolerated dose [s1].
Efficacy pointed the same way. More participants achieved at least a 50% reduction in mean monthly migraine days on atogepant, 64% (173 of 270), than on topiramate, 39% (101 of 257) — a relative risk of 1.6 (95% CI 1.4 to 2.0, p<0.0001) [s1].
How to read it
The finding to hold onto is that this trial's primary endpoint was tolerability, not efficacy — and that is the right question for these two drugs [s1]. Both topiramate and atogepant are established as effective migraine preventives; what separates them in practice is whether a patient can keep taking the drug, and here the newer agent had a clear edge, with roughly a third of topiramate patients stopping over 24 weeks against about one in eight on atogepant [s1].
Two things temper how far to push the result. First, TEMPLE was funded by AbbVie, which markets atogepant, so the comparison was designed and paid for by an interested party — the kind of sponsorship that does not invalidate a trial but does warrant reading the framing with care [s1]. Second, an open-label, single-agent comparison against a drug already notorious for side-effects sets a low bar for the challenger on tolerability; the more informative numbers may be the efficacy gap, which is harder to explain away [s1]. The double-blind period is complete and the open-label phase is ongoing [s1]. It is also worth noting who was studied: the safety population was 89% female and 96% White, so how well the tolerability and efficacy gaps generalise to a more mixed population is not something this trial can answer [s1].
Related coverage has examined how the CGRP-blocking migraine drugs compare across the class and which migraine triggers hold up when they are actually tested.
What to watch
The open-label extension will show whether atogepant's advantage in staying-on-treatment persists past six months, and real-world use will test whether the trial's tolerability gap holds outside a selected trial population [s1]. Cost and access, not efficacy, are likely to decide where each drug lands in practice.
This article describes trial results and is not medical advice. Choice of migraine preventive is a decision for a patient and their clinician.
Sources
- Atogepant versus topiramate in adults with migraine (TEMPLE) — The Lancet Neurology, 23 July 2026
- TEMPLE trial registration (NCT05748483) — ClinicalTrials.gov, first posted 28 February 2023
Sources
- Tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine (TEMPLE): a randomised, head-to-head, phase 3b trial — The Lancet Neurology , July 23, 2026
- Comparative Study of Oral Atogepant Versus Oral Topiramate (TEMPLE, NCT05748483) — ClinicalTrials.gov , February 28, 2023
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