Primary Results of PROMISE-1 (Prevention Of Migraine via Intravenous eptinezumab Safety and Efficacy–1) Trial: a Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab for Prevention of Frequent Episodic Migraines (S20.001)

Objective: Evaluate efficacy and safety of quarterly iv infusion of eptinezumab for prevention of frequent episodic migraine (FEM).

Background: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology. Eptinezumab, a humanized, anti-CGRP monoclonal antibody with 100% bioavailability following iv administration, selectively and potently inhibits CGRP.

Design/Methods: Adults with ≤14 headache days per month, of which ≥4 met ICHD-II criteria for migraine, were randomized to eptinezumab 30, 100, 300 mg, or placebo by iv infusion every 12 weeks. Primary endpoint was reduction in monthly migraine days (MMD) over Weeks 1–12.

Results: Efficacy analysis included 888 patients. Mean baseline MMD were ~8.5 days/month across groups. Eptinezumab 30, 100, and 300 mg vs placebo decreased MMD from baseline over Weeks 1–12 (−4.0 [p=0.0045*], −3.9 [p=0.0179], −4.3 [p=0.0001] vs −3.2, respectively). More patients achieved ≥75% reduction in MMD over Weeks 1–12 with eptinezumab 30, 100, and 300 mg vs placebo (24.7% [p=0.027*], 22.2% [NS], 29.7% [p=0.001] vs 16.2%, respectively). Approximately 50% of patients receiving eptinezumab 30, 100, and 300 mg achieved ≥50% reduction in MMD over Weeks 1–12 (50.2% [p=0.006*], 49.8% [p=0.009*], 56.3% [p<0.001], respectively) vs 37.4%, placebo. The ≥75% responder rates for Weeks 1–4 in the 30-,100-, and 300-mg groups vs placebo were 30.0% (p=0.017*), 30.8% (p=0.011), 31.5% (p=0.007) vs 20.3%, respectively. The probability of migraine at Day 1 following infusion was reduced by 45% (p=0.074), 51.3% (p=0.0167*), and 53.6% (p=0.0087*) with eptinezumab 30, 100, and 300 mg, respectively, vs 20.7%, placebo. Adverse event rates for eptinezumab were similar to placebo.

Conclusions: All doses of eptinezumab significantly reduced migraine activity through 3 months after first infusion in patients with FEM. The probability of migraine was significantly reduced on Day 1 posttreatment and benefits were maintained for 3 months with a single infusion. Adverse event rates were similar to placebo.

Study Supported by:

Financial Support: Funding and support provided by Alder BioPharmaceuticals, Inc., Bothell, WA, USA.

Disclosure: Dr. Saper has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Autonomic Technologies, Eli Lilly, Dr. Reddy, Teva, Supernus Pharm & Migraine Research Foundation. Dr. Lipton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Has reviewed for the NIA and NINDS, serves as consultant, advisory board member, or has received honoraria from: Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmit. Dr. Lipton has received royalty, license fees, or contractual rights payments from Receives royalties from Wolff’s Headache, 8th Edition, Oxford University Press, 2009 and Informa. Dr. Lipton holds stock and/or stock options in Holds stock options in eNeura Therapeutics and Biohaven. Dr. Lipton has received research support from Support from the NIH, the Migraine Research Foundation, the National Headache Foundation, Allergan plc, Amgen, Dr Reddy’s, and Novartis. Dr. Kudrow has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly, Amgen, Alder. Dr. Kudrow has received research support from Amgen, Alder, Eli Lilly, Teva, Zosano, Allergan, Genentech, VM Biopharma, Co-Lucid. Dr. Hirman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder BioPharmaceuticals, Inc. Dr. Dodick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Allergan, Amgen, Alder, Dr Reddy’s, Merck, Dr Reddy’s, Promius, eNeura, Eli Lilly & Company, Insys therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, Boston Scientific, GBS, Colucid, Zosano, Laydenburg Thalmann, Biocentric, Biohaven, Magellan, Pfizer (Japan), Charleston Laboratories. Royalties: Oxford University Press and Cambridge University Press (Book Royalty). Uptodate — editorial/honoraria. CME companies honoraria/publishing honoraria/royalites: Chameleon Communications, Medscape, WebMD, Academy for Continued Healthcare Learning, Haymarket Medical Education, Miller Medical Communications, Global Scientific Communications, HealthLogix, Academy for Continued Healthcare Learning, Meeting LogiX, Health LogiX, . Dr. Silberstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Receives honoraria from Alder Biopharmaceuticals; Allergan, Inc.; Amgen; Avanir Pharmaceuticals, Inc.; eNeura; ElectroCore Medical, LLC; Labrys Biologics; Medscape, LLC; Medtronic, Inc.; Neuralieve; NINDS; Pfizer, Inc.; and Teva Pharmaceuticals. Dr. Silberstein has received research support from His employer receives research support from Allergan, Inc.; Amgen; Cumberland Pharmaceuticals, Inc.; ElectroCore Medical, Inc.; Labrys Biologics; Eli Lilly and Company; Merz Pharmaceuticals; and Troy Healthcare. Dr. Chakhava has nothing to disclose. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder BioPharmaceuticals, Inc.