Oral atogepant reduces monthly migraine, headache
Click Here to Manage Email Alerts
Oral atogepant once per day effectively decreased the number of migraine and headache days over 12 weeks, according to findings from the phase 3 ADVANCE trial that were published in The New England Journal of Medicine.
“Oral CGRP receptor antagonists (gepants) are approved for the treatment of migraine attacks but not for preventive treatment of migraine,” the researchers wrote. “Atogepant is an orally available, small-molecule CGRP receptor antagonist.”
Jessica Ailani, MD, clinical professor of neurology at MedStar's Georgetown University Hospital and director of the MedStar Georgetown Headache Center in Columbia, Md., and colleagues conducted a phase 3, double-masked trial. The researchers randomly assigned adults with four to 14 migraine days per month in a 1:1:1:1 ratio to oral atogepant once per day at a dose of 10 mg, 30 mg or 60 or placebo for 12 weeks.
Change in baseline in the mean number of migraine days per month over 12 weeks served as the primary endpoint. Ailani and colleagues examined headache days per month, a decline from baseline of at least 50% in the 3-month average of migraine days per month, quality of life and scores on the Activity Impairment in Migraine–Diary (AIM-D) as secondary endpoints.
The researchers included 873 patients in the final efficacy analysis (10 mg atogepant group, n = 214; 30 mg atogepant group, n = 223; 60 mg atogepant group, n = 222; placebo group, n = 214). Participants ranged from 18 to 73 years of age (mean age, 41.6 years). The study population comprised primarily women (88.8%) and most were white (83.4%). The mean number of migraine days per month at baseline ranged from 7.5 to 7.9 days across the four groups, according to the study results.
The researchers reported the greatest change from baseline in the mean number of migraine days in the group receiving atogepant 60 mg (4.2 days), followed by 30 mg (3.9 days), 10 mg (3.7 days) and placebo (2.5 days). The mean differences from placebo in the change from baseline were 1.2 days with atogepant 10 mg (95% CI, 1.8 to 0.6), 1.4 days with atogepant 30 mg (95% CI, 1.9 to 0.8) and 1.7 days with atogepant 60 mg (95% CI, 2.3 to 1.2), for a P value of < .001 for all comparisons with placebo.
Results regarding the secondary endpoints “favored atogepant over placebo,” according to the findings from Ailani and colleagues, except for the Activity Impairment in Migraine-Diary performance of daily activities score and the Activity Impairment in Migraine-Diary physical impairment score for the 10 mg dose.
The most frequent adverse events included constipation (6.9% to 7.7% across atogepant doses) and nausea (4.4% to 6.1% across atogepant doses). Serious adverse events included one case each of asthma and optic neuritis in the 10 mg atogepant group, according to the researchers.
Ailani and colleagues acknowledged that the study results “cannot be generalized” to patients with 15 or more headache days per month, as those patients were excluded from the present study. They also noted that the 12-week treatment duration was not sufficient for evaluating the long-term safety of atogepant and its side effects, though the findings from a 52-week trial that will be reported separately were consistent with the current data and no new safety concerns have been reported.
“Oral atogepant once daily was effective in reducing the number of migraine days and headache days over a period of 12 weeks,” the researchers wrote. “Longer and larger trials are needed to determine the effect and safety of atogepant for migraine prevention.”