Orally Administered Atogepant Was Efficacious, Safe, and Tolerable for the Prevention of Migraine: Results From a Phase 2b/3 Study (S17.001)

Objective: To evaluate the efficacy, safety, and tolerability of atogepant versus placebo in a phase 2b/3 trial for prevention of episodic migraine. Background: Atogepant is a novel, oral CGRP receptor antagonist in development for the prevention of migraine. It has high affinity at the human CGRP receptor (K i =15–26 pM) and ~100× lower affinity at the human AMY 1 receptor, estimated terminal half-life ~10 hours, and produces no apparent reactive metabolites. Design/Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (NCT02848326). Adults with a history of migraine, with or without aura, and 4–14 migraine days in the 28-day baseline period were randomized 2:1:2:1:2:1 to placebo, atogepant 10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, or 60 mg BID, respectively, and treated for 12 weeks. Primary efficacy endpoint was change from baseline in mean monthly migraine days. Safety and tolerability were evaluated. Results: Of 834 subjects randomized, 825 composed the safety population and 795 composed the efficacy population. Mean age was 40.1 years; a majority was white (76.1%), female (86.5%), and had never taken preventive treatment for migraine (71.9%). Mean baseline migraine days were 7.67 (SD=2.49). Mean change in migraine days across the 12-week treatment period ( P values versus placebo): placebo (−2.85), atogepant 10 mg QD (−4.00, P =0.0236), 30 mg QD (−3.76, P =0.0390), 30 mg BID (−4.23, P =0.0034), 60 mg QD (−3.55, P =0.0390), 60 mg BID (−4.14, P =0.0031). Treatment-emergent AEs were reported by 480 subjects (58.2%); for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, none considered treatment-related. There were 10 cases of treatment-emergent ALT/AST elevations >3× the upper limit of normal, balanced across groups. Conclusions: All 5 atogepant treatment arms showed statistically significant, clinically relevant differences from placebo in reductions from baseline in mean migraine days. Atogepant was well tolerated, with no treatment-related serious AEs. Disclosure: Dr. Goadsby has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen Eli-Lilly and Company, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Dr Reddy’s Laboratories, Electrocore LLC, eNeura, Novartis, Scion, Teva Pharmaceuticals, and Trigemina Inc. Dr. Goadsby has received personal compensation in an editorial capacity for Journal Watch- Massachusetts Medical Society. Dr. Goadsby has received research support from Amgen and Eli-Lilly and Company. Dr. Dodick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dodick reports personal fees from Acorda, Amgen, Alder, Allergan, Autonomic Technologies, Biohaven, Colucid, Eli Lilly, eNeura, Foresight Capital, Neurolief, Zosano, WL Gore, Vedanta Associates, Promius Pharma, Magellan Healthcare, CC West Ford Group, Nocira, Novartis, NuPathe, Supernus, Electrocore, Tonix, Teva, Alcobra, Insys, Ipsen, Charleston Laboratories, Biocentric, Theranica, Xenon. ZP Opco. Travel expense reimbursement and speaking fee from Sun Pharma. Anticipated income from consulting within next 3 weeks not previously reported: Impel pharmaceuticals (currently under review by Mayo Clinic Medical Industry Relations Committee). Compensation for activities related to data safety monitoring committee from Axsome. Speaking fees, or fees related to CME content development: Healthlogix, Medicom Worldwide, Medlogix Communications, MedNet, Miller Medical Communications, PeerView Operation Services America, Web MD/Medscape, American Academy of Neurology, American Headache Society, PeerView Institute for Medical Education, Chameleon Communications, Academy for Continued Healthcare Learning, Universal Meeting Management, Haymarket Medical Education, Global Scientific Communications, UpToDate, Meeting LogiX. Consulting use agreement through employer: NeuroAssessment Systems, Myndshft. Dr. Dodick has received compensation for serving on the Board of Directors of Board of Directors position: King-Devick Technologies, Ontologics. Dr. Dodick holds stock and/or stock options in Hold equity in: Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, Epien, which sponsored research in which Dr. Dodick was involved as an investigator. Dr. Dodick holds stock and/or stock options in Hold equity in: Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, and Epien. Dr. Trugman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Trugman holds stock and/or stock options in Allergan plc. which sponsored research in which Dr. Trugman was involved as an investigator. Dr. Trugman holds stock and/or stock options in Allergan plc. Dr. Finnegan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Finnegan holds stock and/or stock options in Allergan plc. which sponsored research in which Dr. Finnegan was involved as an investigator. Dr. Finnegan holds stock and/or stock options in Allergan plc. Dr. Likis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Likis holds stock and/or stock options in Allergan plc. which sponsored research in which Dr. Likis was involved as an investigator. Dr. Likis holds stock and/or stock options in Allergan plc.. Dr. Lu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Lu holds stock and/or stock options in Allergan plc. which sponsored research in which Dr. Lu was involved as an investigator. Dr. Lu holds stock and/or stock options in Allergan plc.. Dr. Szegedi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as a full-time employee of Allergan plc and stockholder of Allergan and Merck.