Historically, migraine prevention has been managed with a wide variety of non-migraine-specific drug classes, such as beta-adrenergic receptor blockers, calcium antagonists, antidepressants, and anti-epileptics including topiramate.
However, many of these oral preventive treatments have been associated with poor side-effect profiles, and key opinion leaders (KOLs) previously interviewed by GlobalData reported that low efficacy of oral preventive treatment was common among patients, meaning that patients often cycle through the different drug classes of oral preventive treatments.
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The first preventive therapies developed specifically for the treatment of migraine were the anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) including Amgen’s Aimovig (erenumab), followed by the oral gepants, including AbbVie’s Qulipta (atogepant); however, they are typically prescribed as second- or third-line options for many patients due to reimbursement restrictions requiring failures with the non-migraine-specific oral preventives before they can be prescribed.
On 22 April, at the 2026 American Academy of Neurology (AAN) meeting, during a poster session, AbbVie presented results from the Phase IIIb TEMPLE study (NCT05748483), which was a head-to-head study directly comparing 60mg once-daily Qulipta and the highest tolerated dose of topiramate (50, 75, or 100mg/day), with trial sites across Europe and Canada.
The primary endpoint of the TEMPLE study was focused on safety, looking at treatment discontinuation due to treatment-emergent adverse events (TEAEs). Across the 24-week, double-blind treatment phase, significantly fewer treatment discontinuations were seen in the Qulipta group (12.1%) compared with the topiramate group (29.6%). Qulipta further demonstrated its superior tolerability with a lower incidence of TEAEs compared with topiramate.
Key secondary endpoints from the TEMPLE study demonstrated the superior efficacy of Qulipta compared with topiramate. In the double-blind treatment completers population, 73.7% of patients in the Qulipta group achieved a greater than 50% reduction in mean monthly migraine days (MMDs) during Months 4–6, compared with 48.5% in the topiramate group. Qulipta also demonstrated a greater reduction in change from baseline in MMDs during Months 4–6 compared to topiramate. Qulipta faces significant competition in the migraine prevention space from Pfizer’s Nurtec (rimegepant) and the anti-CGRP mAbs.
To date, Amgen’s Aimovig (erenumab) is the only other anti-CGRP therapy with head-to-head trial data comparing it to traditional oral preventive drugs. In the Phase IV HER-MES trial (NCT03828539), Aimovig was shown to be more effective and better tolerated than topiramate. On 22 April at AAN 2026, AbbVie presented a poster comparing Qulipta and Aimovig through an indirect comparison of the TEMPLE and HER-MES trials. The safety and tolerability throughout 24 weeks of Qulipta and Aimovig were comparable. When looking at the overall patient population, Qulipta demonstrated a statistically significant greater odds of a reduction of greater than 50% in mean MMDs across Month 1 compared with Aimovig; however, across Months 4–5, the odds of reduction were comparable. The change from baseline in MMDs across Month 1 and Months 4–6 were also comparable for Qulipta and Aimovig, demonstrating that the two drugs have similar efficacy, although Qulipta may demonstrate an earlier onset of that efficacy compared with Aimovig. Similar results were seen when looking at a subgroup of patients with 8–14 baseline MMDs.
These comparable efficacy and safety results highlight that patient preference for administration could be the key driver in drug choice, with Qulipta being a once-daily oral drug compared with the monthly subcutaneous dosing of Aimovig.
In the US, a 2024 statement was published by the American Headache Society recommending that the anti-CGRP mAbs and gepants should be used as first-line preventive options due to their superior efficacy and tolerability compared with the oral preventive options. Not only do the TEMPLE results support the American Headache Society’s position, but they provide AbbVie with the clinical evidence base needed to challenge the step-through reimbursement requirements that have restricted Qulipta’s uptake in Europe, where payers have demanded failure on established oral preventives before approving newer agents. Whether this head-to-head evidence is sufficient to unlock broader reimbursement given the comparative costs of the non-migraine-specific oral preventives and the anti-CGRP therapies will depend on payer willingness to accept tolerability-driven discontinuation as a primary endpoint rather than a secondary commercial argument.
