Objective:

To evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of migraine. 

Background:

Atogepant is an oral, small molecule, calcitonin gene-related peptide receptor antagonist.

Design/Methods:

Phase 3, multicenter, double-blind trial (NCT03777059). Adults with 4-14 migraine days per month were randomized 1:1:1:1 to atogepant 10mg, atogepant 30mg, atogepant 60mg, or placebo once daily for 12 weeks. The primary efficacy endpoint was a change from baseline in mean monthly migraine days (MMDs) across the 12-week treatment period. A key secondary endpoint was the proportion of participants with ≥50% reduction in their 3-month average of MMDs.

Results:

The trial included 910 randomized participants (n=902 safety population, n=873 modified intent-to-treat population); >87% of participants completed the treatment period across all groups. Participants were on average 42 years old, 89% female, and 83% white; mean BMI was 31 kg/m². Mean changes from baseline in MMDs were -3.69 for atogepant 10mg, -3.86 for atogepant 30mg, -4.20 for atogepant 60mg versus -2.48 placebo (p<0.0001 all doses). The percentage of participants who achieved a ≥50% reduction in their 3-month average of MMDs for atogepant were 56% for 10mg, 59% for 30mg, 61% for 60mg versus 29% for placebo (p<0.0001 all doses). AEs were reported by 52%-54% of participants in atogepant groups and 57% in the placebo group. The most commonly reported AEs were constipation (7%-8% across doses vs 0.5% placebo) and nausea (4%-6% across doses vs 2% placebo); none were serious. In atogepant 10mg and placebo, 0.9% reported serious AEs; none were reported for 30mg or 60mg. Discontinuations due to AEs were 2%-4% in atogepant groups, and 3% in placebo. No hepatic safety issues were identified following daily dosing with atogepant.

Conclusions:

Atogepant provided statistically significant and clinically meaningful reductions in mean monthly migraine days in the ADVANCE trial. Atogepant was safe and well-tolerated.