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By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
A new class of drug has been approved for the preventive treatment of migraine in adults. Erenumab-aooe is a fully human monoclonal antibody and is the first-in-class calcitonin gene-related peptide (CGRP) receptor antagonist. It is marketed as Aimovig.
Erenumab-aooe is indicated for the preventive treatment of migraine in adults.1
The recommended dose is 70 mg given subcutaneously once monthly.1 Some patients may need 140 mg (two injections of 70 mg) once monthly. Erenumab-aooe is available as a 70 mg single-dose prefilled syringe or autoinjector (SureClick).
Erenumab-aooe, with a novel mechanism of action, is the first drug approved specifically for the preventive treatment of migraine.
Erenumab-aooe must be administered by injection. Injection site reactions and constipation are the most common side effects (3-5%). The long-term safety of erenumab-aooe remains to be established.
CGRP is believed to be a key mediator in migraine headaches, suggesting that targeting the CGRP receptor may be an effective approach in preventing migraine.2 The efficacy of erenumab-aooe was evaluated in three randomized, double-blind, placebo-controlled studies.1,3,4 Two were in subjects with episodic migraine (four to 14 migraine days per month) and one in subjects with chronic migraine (≥ 15 headache days and ≥ 8 migraine days per month).
In the first six-month study, subjects were randomized to erenumab-aooe 70 mg (n = 317), 140 mg (n = 319), or placebo (n = 319).1,3 Migraine-specific medications such as triptans, ergotamine derivative, and nonsteroidal anti-inflammatory drugs were allowed during the study. The primary efficacy endpoint was change from baseline in mean monthly migraine days (MMD) over months four to six. A migraine day was defined as any calendar day that the patient had onset, continuation, or recurrence of a migraine lasting at least 30 minutes and manifesting with at least two pain features, at least one associated nonpain feature, or both.3 Secondary endpoints included the percentage of subjects achieving ≥ 50% reduction from baseline in mean monthly migraine days (% responders) and change from baseline in mean monthly acute migraine-specific medications over months 4 to 6. At baseline, the mean migraine frequency was about eight days per month, and approximately 39% had a history of preventive treatment failure due to lack of effectiveness or intolerance.
Erenumab-aooe 70 mg reduced MMD by a mean of 3.2 days, while 140 mg reduced MMD by 3.7 days, compared to -1.8 days for placebo, a difference from placebo of -1.4 and -1.9, respectively (both P < 0.001). Response was achieved at the first efficacy time point of one month. Percent responders were 43.3% and 50% for erenumab-aooe compared to 26.6% for placebo. Difference in monthly acute migraine-specific medication days were -0.9 and -1.4 (P <0.001). Physical impairment and everyday activity scores also improved significantly with both doses of erenumab-aooe.
The second study was a three-month investigation of erenumab-aooe 70 mg (n = 286) and placebo (n = 291) in subjects with episodic migraine (approximately eight migraine days per month).1,4 At month 3, the difference between drug and placebo was -1.0 MMD (P < 0.001). The percent responders were 39.7% vs. 29.5% (P = 0.01). The difference in monthly migraine-specific medication days was -0.6 (P = 0.002). However, erenumab-aooe did not significantly improve everyday activity or physical impairment scores.
In subjects with chronic migraine (mean of 18 MMD at baseline), erenumab-aooe 70 mg and 140 mg both reduced MMD by 2.5 days compared to placebo. Percent responders were 40-41% compared to 23.5% for placebo. The difference in monthly medication days were -1.9 and -2.6 (P < 0.001). Recently, Novartis released results from a study assessing the effectiveness of erenumab-aooe in subjects who experienced two to four previous preventive treatment failures.5 Thirty percent responded to erenumab-aooe compared to 14% for placebo. Erenumab-aooe appears to be well tolerated. Less than 3% of subjects withdrew from the six-month trial because of adverse reactions.2 Anti-erenumab-aooe antibodies developed in about 5% of subjects and < 0.1% exhibited in vitro neutralizing activity. However, this may be underestimated because of the limitation of the assay.1
It is estimated that close to 40% of migraineurs need preventive therapy.6 Current evidence-based guidelines of the American Academy of Neurology and the American Headache Society list antiepileptics (divalproex sodium, sodium valproate, topiramate) and beta-blockers (propranolol, timolol, metoprolol) as pharmacologic migraine prophylaxis with established efficacy.6 Erenumab-aooe provides a novel drug for preventing migraine headaches. The list price is $575 for one month.
Financial Disclosure: Internal Medicine Alert’s Physician Editor Stephen Brunton, MD, is a retained consultant for Abbott Diabetes, GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Salix, Allergan, Janssen, Lilly, Novo Nordisk, and Sanofi; he serves on the speakers bureau of Salix, Allergan, Janssen, Lilly, Sanofi, Novo Nordisk, AstraZeneca, and Boehringer Ingelheim. Peer Reviewer Gerald Roberts, MD; Editor Jonathan Springston; Executive Editor Leslie Coplin; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.