BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related 
peptide receptor antagonist that is being investigated for the preventive 
treatment of migraine.
METHODS: In a phase 3, double-blind trial, we randomly assigned adults with 4 to 
14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of 
oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. The primary end 
point was the change from baseline in the mean number of migraine days per month 
across the 12 weeks. Secondary end points included headache days per month, a 
reduction 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).
RESULTS: A total of 2270 participants were screened, 910 were enrolled, and 873 
were included in the efficacy analysis; 214 were assigned to the 10-mg atogepant 
group, 223 to the 30-mg atogepant group, 222 to the 60-mg atogepant group, and 
214 to the placebo group. The mean number of migraine days per month at baseline 
ranged from 7.5 to 7.9 in the four groups. The changes from baseline across 12 
weeks were -3.7 days with 10-mg atogepant, -3.9 days with 30-mg atogepant, -4.2 
days with 60-mg atogepant, and -2.5 days with placebo. The mean differences from 
placebo in the change from baseline were -1.2 days with 10-mg atogepant (95% 
confidence interval [CI], -1.8 to -0.6), -1.4 days with 30-mg atogepant (95% CI, 
-1.9 to -0.8), and -1.7 days with 60-mg atogepant (95% CI, -2.3 to -1.2) 
(P<0.001 for all comparisons with placebo). Results for the secondary end points 
favored atogepant over placebo with the exceptions of the AIM-D Performance of 
Daily Activities score and the AIM-D Physical Impairment score for the 10-mg 
dose. The most common adverse events were 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.
CONCLUSIONS: Oral atogepant once daily was effective in reducing the number of 
migraine days and headache days over a period of 12 weeks. Adverse events 
included constipation and nausea. Longer and larger trials are needed to 
determine the effect and safety of atogepant for migraine prevention. (Funded by 
Allergan; ADVANCE ClinicalTrials.gov number, NCT03777059.).