In the phase 3 ADVANCE trial (NCT03622905), treatment with the calcitonin gene-related peptide (CGRP) receptor antagonist atogepant(AbbVie Inc, North Chicago, IL) made a significantly greater reduction in mean monthly migraine days, compared with placebo, for all doses across the 12-week treatment period.
All atogepant dose groups demonstrated statistically significantly greater decreases in mean monthly migraine days compared with placebo. Participants treated in the 10 mg, 30 mg, 60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days, respectively, all compared with participants in the placebo arm, who experienced a decrease of 2.48 days (all dose groups vs placebo, P=<.0001).
The pivotal phase 3 multicenter randomized double-blind placebo-controlled parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those with 4 to 14 migraine days per month. A total of 910 participants were randomized to 1 of 4 treatment groups evaluating 10 mg, 30 mg, or 60 mg of atogepant once daily, or placebo. Efficacy analyses were based on the modified intent-to-treat (mITT) population of 873 participants.
No new safety risks were observed compared to the safety profile observed in the previous trial evaluating atogepant. Serious adverse events occurred in 0.9% of participants treated in the atogepant 10 mg arm compared with 0.9% of participants in the placebo arm. No participants in the atogepant 30 mg or 60 mg treatment arms experienced a serious adverse event. The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation (6.9-7.7% across all doses vs 0.5% for placebo), nausea (4.4% - 6.1% across all doses vs 1.8% for placebo), and upper respiratory tract infection (3.9% - 5.7% across all doses vs 4.5% for placebo). The majority of cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation.
"Migraine attacks can be debilitating, but migraine is a treatable disease, and people living with it are not alone in their battle to control it," said Thomas J. Hudson, MD, senior vice president of R&D and chief scientific officer, AbbVie. "With the results from these trials, we aim to provide a safe and effective preventive treatment that offers patients and healthcare providers a simple, once daily oral treatment that works specifically by blocking CGRP receptors and preventing migraine."
Peter McAllister, MD
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD