Atogepant Safe, Effective in Treatment-Resistant Episodic Migraine: Daily Dose

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Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

Last week, we reported on findings from a study published in The Lancet Neurology that examined the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in patients for whom 2 to 4 classes of conventional oral preventive treatments have failed.

The study

The phase 3b ELEVATE trial was a randomized, double-blind, placebo-controlled parallel-group study conducted at 73 study sites in North America and Western and Eastern Europe. Investigators randomly assigned adults aged 18 to 80 years with episodic migraine resistant to up to 4 classes of oral migraine preventives, in 1:1 fashion, to receive either atogepant 60 mg or placebo once a day for 12 weeks. They further stratified the treatment group by baseline number of migraine days per month, number of ineffective treatment classes, and by geographic region.

A total of 309 participants in the off-treatment hypothetical estimand (OTHE) population were randomly assigned to the same treatment regimens.

The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the OTHE population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for at least 1 of the 4-week post-baseline periods (whether on treatment or off treatment).

Researchers screened 540 participants between March 5, 2021, and August 4, 2022, finally randomly assigning 315 to active or placebo treatment; 313 participants (89% women, 96% White) received at least 1 dose of atogepant.

The findings

Among the 309 participants in the OTHE population, researchers reported least squares mean (LSM) changes from baseline in monthly migraine days across 12 weeks of −1.9 (standard error 0.4) with placebo and −4.2 (SE 0.4) with atogepant 60 mg (LSM difference −2.4; 95% CI −3.2 to −1.5; adjusted P <.001).

Among atogepant-treated participants diarrhea was the most common treatment-emergent adverse event, reported by 10% vs by 3% of participants receiving placebo. There were 4 serious adverse events among 156 participants in the atogepant group and none in the placebo group. Treatment-emergent adverse events resulting in discontinuation were reported in 3 participants in the atogepant group and 2 in the placebo group.

Authors' comment

"This is, to our knowledge, the first study for an oral, small molecule [calcitonin gene-related peptide] receptor antagonist to show high efficacy, safety and tolerability for this difficult-to-treat population. Atogepant may be an effective preventive treatment option.”

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