Atogepant Significantly Reduces Mean Monthly Migraine Days in the Phase 3 Trial (ADVANCE) for the Preventive Treatment of Migraine
Jessica Ailani1, Richard Lipton2, Peter Goadsby3, Hua Guo4, Rosa Miceli4, Lawrence Severt4, Michelle Finnegan4, Joel Trugman4
1Medstar Georgetown Neurology, 2Albert Einstein College of Medicine, 3University of California, Los Angeles, 4AbbVie
To evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of migraine. 
Atogepant is an oral, small molecule, calcitonin gene-related peptide receptor antagonist.
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.
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.
Atogepant provided statistically significant and clinically meaningful reductions in mean monthly migraine days in the ADVANCE trial. Atogepant was safe and well-tolerated.