Efficacy, Safety, and Tolerability of Ubrogepant for the Acute Treatment of Migraine: Results From a Single-Attack Phase 3 Study, ACHIEVE II (S38.008)

Objective: To evaluate the efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine.

Background: Ubrogepant, a novel, orally active, calcitonin gene–related peptide receptor antagonist, is in development for the acute treatment of migraine.

Design/Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Adults with a history of migraine were randomized (1:1:1) to placebo or ubrogepant (25mg or 50mg). Patients had 60 days to treat a single migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2h post initial dose) were headache pain freedom and absence of the most bothersome migraine-associated symptom (MBS) identified before treatment. Secondary efficacy endpoints included pain relief, sustained pain relief, sustained pain freedom, and absence of individual migraine-associated symptoms.

Results: 1686 patients were randomized (n=1465, safety population; n=1355, mITT population). Mean age: 41 years; majority white (81%) and female (89%). Compared with placebo, significantly greater proportions of ubrogepant-treated patients achieved 2-hour pain freedom (both ubrogepant doses [placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129]) and 2-hour absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). All secondary efficacy endpoints (except absence of nausea at 2h) met statistical significance versus placebo for the 50mg dose. Pain relief rates (2h) were higher for ubrogepant 50mg than placebo (62.7% vs 48.2%, adjusted P=0.0129). Secondary efficacy outcomes were not significant for the 25mg dose. Ubrogepant’s and placebo’s AE profiles were similar.

Conclusions: In ACHIEVE II, both co-primary efficacy endpoints were met, with clinically meaningful effects for the 50mg ubrogepant dose. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom but not the MBS co-primary endpoint. Additionally, 62.7% of ubrogepant-treated patients who received 50mg achieved pain relief at 2h. Ubrogepant was well tolerated. These results confirm those previously reported (ACHIEVE I), together supporting the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine.

Disclosure: 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. 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. Ailani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder, Allergan, Amgen, Avanir, Biohavin, Eli Lilly and Company, Electrocore, Promius, Teva, Impel, Satsuma, Aptus, Alpha Sites and Miller Medical Communications. Dr. Ailani has received personal compensation in an editorial capacity for Current Pain and Headache Reports (section editor). Dr. Ailani has received research support from ARMR/American Migraine Foundation and Biohaven. 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. 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. 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. 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. Dr. Lipton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with American Academy of Neurology, Alder Biopharmaceuticals, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir Pharmaceuticals, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, and Vedanta. Dr. Lipton holds stock and/or stock options in Biohaven.