TY - JOUR
T1 - Eptinezumab for prevention of chronic migraine
T2 - A randomized phase 2b clinical trial
AU - Dodick, David W.
AU - Lipton, Richard B.
AU - Silberstein, Stephen
AU - Goadsby, Peter J.
AU - Biondi, David
AU - Hirman, Joe
AU - Cady, Roger
AU - Smith, Jeff
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was sponsored and funded, and its publication supported by Alder BioPharmaceuticals, Inc (Bothell, WA, USA). The sponsor participated in the design and conduct of the study; data collection, management, analysis, and interpretation; and preparation, review, and approval of the manuscript. All statistical analyses were performed by a contracted research organization and were directed or designed by Pacific Northwest Statistical Consulting under contractual agreement with Alder BioPharmaceuticals. All authors and Alder BioPharmaceuticals prepared, reviewed, and approved the manuscript and made the decision to submit the manuscript for publication. Editorial support for the development of this manuscript was funded by Alder BioPharmaceuticals and was provided by BioScience Communications (New York, NY, USA) and The Medicine Group (New Hope, PA, USA).
Publisher Copyright:
© International Headache Society 2019.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Background: Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. Objective: To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. Methods: This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial. Men and women (N = 616) aged 18–55 years were included if they had a diagnosis of chronic migraine, with onset at age ≤35 years and history of chronic migraine ≥1 year. During the 28-day screening period, patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks as recorded in the electronic diary. Patients were assigned in a 1:1:1:1:1 ratio to eptinezumab 300, 100, 30, 10 mg or placebo, administered as a single IV infusion. The primary endpoint was the percentage of patients with a ≥75% decrease in monthly migraine days over weeks 1–12 compared with the 28-day screening period. Results: The ≥75% migraine responder rates over weeks 1–12 for eptinezumab 300, 100, 30, and 10 mg were 33.3%, 31.4%, 28.2%, and 26.8%, respectively, versus 20.7% for placebo (p = 0.033, 0.072, 0.201, 0.294 vs. placebo). Secondary efficacy endpoints (e.g. ≥50% responder rate, change from baseline in frequency of migraine/headache days, and percentage of severe migraines) had results favoring the three higher eptinezumab doses versus placebo. Eptinezumab was well tolerated and adverse event rates were similar to placebo. Conclusions: The results of this trial demonstrate that eptinezumab appears effective and well-tolerated for the preventive treatment of chronic migraine and justifies the conduct of pivotal phase 3 trials for migraine prevention. Trial Registration: ClinicalTrials.gov identifier: NCT02275117.
AB - Background: Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. Objective: To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. Methods: This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial. Men and women (N = 616) aged 18–55 years were included if they had a diagnosis of chronic migraine, with onset at age ≤35 years and history of chronic migraine ≥1 year. During the 28-day screening period, patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks as recorded in the electronic diary. Patients were assigned in a 1:1:1:1:1 ratio to eptinezumab 300, 100, 30, 10 mg or placebo, administered as a single IV infusion. The primary endpoint was the percentage of patients with a ≥75% decrease in monthly migraine days over weeks 1–12 compared with the 28-day screening period. Results: The ≥75% migraine responder rates over weeks 1–12 for eptinezumab 300, 100, 30, and 10 mg were 33.3%, 31.4%, 28.2%, and 26.8%, respectively, versus 20.7% for placebo (p = 0.033, 0.072, 0.201, 0.294 vs. placebo). Secondary efficacy endpoints (e.g. ≥50% responder rate, change from baseline in frequency of migraine/headache days, and percentage of severe migraines) had results favoring the three higher eptinezumab doses versus placebo. Eptinezumab was well tolerated and adverse event rates were similar to placebo. Conclusions: The results of this trial demonstrate that eptinezumab appears effective and well-tolerated for the preventive treatment of chronic migraine and justifies the conduct of pivotal phase 3 trials for migraine prevention. Trial Registration: ClinicalTrials.gov identifier: NCT02275117.
KW - 100% responder rates
KW - 50% responder rates
KW - 75% responder rates
KW - ALD403
KW - Eptinezumab
KW - anti-CGRP monoclonal antibody
KW - chronic migraine
KW - clinical trial
KW - preventive migraine treatment
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U2 - 10.1177/0333102419858355
DO - 10.1177/0333102419858355
M3 - Article
C2 - 31234642
AN - SCOPUS:85068175745
SN - 0333-1024
VL - 39
SP - 1075
EP - 1085
JO - Cephalalgia
JF - Cephalalgia
IS - 9
ER -