Atogepant Significantly Reduces Mean Monthly Migraine Days in the Phase 3 Trial (ADVANCE) for the Preventive Treatment of Migraine (1494)

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.

Disclosure: Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck/Alder. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vorso. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CtrlM. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Allergan/abbive. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biohaven. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amgen. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck/Alder. Dr. Ailani has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Report. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. Dr. Ailani has received stock or an ownership interest from Ctrl M. The institution of Dr. Ailani has received research support from Allergan/Abbvie. The institution of Dr. Ailani has received research support from Eli Lilly. The institution of Dr. Ailani has received research support from Zosano. Dr. Ailani has received research support from Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Speaker, Advisory Panel with Medscape. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Medical Advisor with SELF. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has received stock or an ownership interest from eNeura. Dr. Lipton has received stock or an ownership interest from Biohaven. Dr. Lipton has received stock or an ownership interest from CtrlM Health. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alder Biopharmaceuticals. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clexio. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli-Lilly. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epalex. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Neuropharma. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Santara Therapeutics. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Goadsby has received research support from Celgene. The institution of Dr. Goadsby has received research support from Eli-Lilly. The institution of Dr. Goadsby has received research support from Visual Snow Initiative. Dr. Goadsby has received intellectual property interests from a publication relating to health care. Dr. Goadsby has received intellectual property interests from a publication relating to health care. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with Diamond Headache Clinic. Dr. Goadsby has a non-compensated relationship as a Trustee with Migraine Trust that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Trustee with Organisation for Understanding Cluster Headache (UK) that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Chair with PICORI MOTS DSMB that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a President with American Headache Society that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Scientific Officer with British Association for the Study of Headache that is relevant to AAN interests or activities. Hua Guo has received personal compensation for serving as an employee of AbbVie. Hua Guo has received stock or an ownership interest from AbbVie. Rosa Miceli has received personal compensation for serving as an employee of AbbVie . Rosa Miceli has received stock or an ownership interest from AbbVie . Lawrence Severt has nothing to disclose. Michelle Finnegan has received personal compensation for serving as an employee of AbbVie. Dr. Trugman has received personal compensation for serving as an employee of AbbVie. Dr. Trugman has received stock or an ownership interest from AbbVie.