Rates of Response to Atogepant for Migraine Prophylaxis Among Adults: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Some patients with migraine, particularly those in primary care, require effective, well-tolerated, migraine-specific oral preventive treatments.

Objective: To examine the efficacy of atogepant, an oral, small-molecule, calcitonin gene-related peptide receptor antagonist, using 4 levels of mean monthly migraine-day (MMD) responder rates.

Design, setting, and participants: This secondary analysis of a phase 3, double-blind, placebo-controlled randomized clinical trial evaluated the efficacy and safety of atogepant for the preventive treatment of migraine from December 14, 2018, to June 19, 2020, in adults with 4 to 14 migraine-days per month at 128 sites in the US.

Interventions: Patients were administered 10 mg of atogepant (n = 222), 30 mg of atogepant (n = 230), 60 mg of atogepant (n = 235), or placebo (n = 223) once daily in a 1:1:1:1 ratio for 12 weeks.

Main outcomes and measures: These analyses evaluated treatment responder rates, defined as participants achieving 50% or greater (α-controlled, secondary end point) and 25% or greater, 75% or greater, and 100% (prespecified additional end points) reductions in mean MMDs during the 12-week blinded treatment period.

Results: Of 902 participants (mean [SD] age, 41.6 [12.3] years; 801 [88.8%] female; 752 [83.4%] White; 825 [91.5%] non-Hispanic), 873 were included in the modified intention-to-treat population (placebo, 214; 10 mg of atogepant, 214; 30 mg of atogepant, 223; and 60 mg of atogepant, 222). For the secondary end point, a 50% or greater reduction in the 12-week mean of MMDs was achieved by 119 of 214 participants (55.6%) treated with 10 mg of atogepant (odds ratio, 3.1; 95% CI, 2.1-4.6), 131 of 223 participants (58.7%) treated with 30 mg atogepant (odds ratio, 3.5; 95% CI, 2.4-5.3), 135 of 222 participants (60.8%) treated with 60 mg of atogepant (odds ratio, 3.8; 95% CI, 2.6-5.7), and 62 of 214 participants (29.0%) given placebo (P < .001). The numbers of participants who reported a 25% or greater reduction in the 12-week mean of MMDs were 157 of 214 (73.4%) for 10 mg of atogepant, 172 of 223 (77.1%) for 30 mg of atogepant, and 180 of 222 (81.1%) for 60 mg of atogepant vs 126 of 214 (58.9%) for placebo (P < .002). The numbers of participants who reported a 75% or greater reduction in mean MMDs were 65 of 214 (30.4%) for 10 mg of atogepant, 66 of 223 (29.6%) for 30 mg of atogepant, and 84 of 222 (37.8%) for 60 mg of atogepant compared with 23 of 214 (10.7%) for placebo (P < .001). The numbers of participants reporting 100% reduction in mean MMDs were 17 of 214 (7.9%) for 10 mg of atogepant (P = .004), 11 of 223 (4.9%) for 30 mg of atogepant (P = .02), and 17 of 222 (7.7%) for 60 mg of atogepant (P = .003) compared with 2 of 214 (0.9%) for placebo.

Conclusions and relevance: At all doses, atogepant was effective during the 12-week double-blind treatment period beginning in the first 4 weeks, as evidenced by significant reductions in mean MMDs at every responder threshold level. Higher atogepant doses appeared to produce the greatest responder rates, which can guide clinicians in individualizing starting doses.

Trial registration: ClinicalTrials.gov Identifier: NCT03777059.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lipton reported receiving personal fees for study design, data analysis, and attending advisory board service from Allergan/AbbVie during the conduct of the study and grants and nonfinancial support from Allergan/AbbVie, grants and personal fees from Amgen, personal fees from Eli Lilly, grants, personal fees, and stocks/stock options from Biohaven, grants and personal fees from GlaxoSmithKline, personal fees from Impel, grants from BioDelivery Sciences International, grants and personal fees from Teva, stock options and grants from Manistee, and stock options from Ctrl M Health outside the submitted work. Dr Pozo-Rosich reported receiving personal fees from AbbVie, personal fees from Eli Lilly, personal fees and grants from Novartis, personal fees and grants from Teva Pharmaceuticals, personal fees from Lundbeck, personal fees from Medscape, and grants from AbbVie outside the submitted work. Dr Blumenfeld reported receiving speaking and consulting fees from Allergan/AbbVie outside the submitted work and performing promotional speaking and consulting for Allergan and AbbVie. Dr Dodick reported receiving personal fees from Amgen, CapiThera, Ceruvia Lifesciences, Cerecin, Cooltech, AbbVie, Allergan, Ctrl M Health, Biohaven, Novartis, Lundbeck, Eli Lilly, GlaxoSmithKline, Impel, Theranica, Satsuma, WL Gore, Genentech, Perfood, Praxis, Nocira, Pfizer, Revance, AYYA Biosciences, Eli Lilly, Oxford University Press, Cambridge University Press, American Academy of Neurology, Headache Cooperative of the Pacific, MF Medical Education Research, Biopharm Communications, CEA Group Holding Company (Clinical Education Alliance LLC), Teva, Amgen, Lundbeck, Vector Psychometric Group, Wolters Kluwer, WebMD Health/Medscape, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Synapse, Miller Medical Communications, MJH Life Sciences, AEON, Medica Communications LLC, KLJ Associates, Medlogix Communications, Global Access Meetings, Majallin LLC, Academy for Continued Healthcare Learning, Autonomic Technologies, Axsome, Dr Reddy's/Promius, Electrocore LLC, eNeura, Neurolief, Ipsen, Supernus, Sun Pharma, Charleston Laboratories, Alder, Vedanta, Zosano, ZP Opco, XoC, Foresight Capital, Oppenheimer, Chameleon, Haymarket, UpToDate, Clexio, LinPharma, Pieris, and Equinox outside the submitted work; in addition, Dr Dodick reported having a patent issued for Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis; receiving royalties from Wolters Kluwer, Oxford University Press, and Cambridge University Press; having nonprofit board membership in the American Brain Foundation, American Migraine Foundation, ONE Neurology, Precon Health Foundation, International Headache Society Global Patient Advocacy Coalition, Atria Health Collaborative, Domestic Violence HOPE Foundation/Panfila, CSF Leak Foundation, and Love of The Game; receiving research support from the US Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, and Patient Centered Outcomes Research Institute; and having stock options, being a shareholder, having patents, or being a member of the board of directors for Ctrl M Health (options), Aural Analytics (options), ExSano (options), Palion (options), Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/board), Nocira (options), Matterhorn (shares/board), Ontologics (shares/board), King-Devick Technologies (options/board), Precon Health (options/board), AYYA Biosciences (options), Axon Therapeutics (options/board), Cephalgia Group (options/board), and Atria Health (options/salary). Dr Lu reported owning restricted stocks in AbbVie. Dr Dabruzzo reported owning stock in AbbVie. Dr Miceli reported receiving personal fees from AbbVie until September 2021 outside the submitted work. Dr Trugman reported holding stock and receiving nonfinancial support from AbbVie. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants Through the Trial

DBTP indicates double-blind treatment period; mITT, modified intention-to-treat.

Figure 2.. Proportions of Participants Achieving Various Responder Rates by Treatment Group: 12-Week Mean Responder Rates (Modified Intention-to-Treat Population)

aP < .05 vs placebo. bP < .01 vs placebo. cP < .001 vs placebo.

Figure 3.. Proportions of Participants Achieving Various Responder Rate Reductions by Treatment Group and 4-Week Intervals (Modified Intention-to-Treat Population)

MMD indicates monthly migraine-day. aP < .01 vs placebo. bP < .001 vs placebo. cP < .0001 vs placebo.

Figure 4.. Proportions of Participants Achieving Specified Levels of Reduction in Mean Monthly Migraine-Days (MMDs) During 12 Weeks (Modified Intention-to-Treat Population)