The latest New Drug Review covers Amgen’s migraine medication.
In May, the FDA approved erenumab-aooe (Aimovig, Amgen Inc.) for prevention of migraine in adults. It is a human immunoglobulin G2 monoclonal antibody that binds and antagonizes the function of the calcitonin gene-related peptide (CGRP) receptor. CGRP receptor antagonists can reduce the vasodilation and inflammation associated with the pathophysiology of migraines, which can result in fewer migraines.1,2
Erenumab-aooe was evaluated for prevention of episodic migraine in two studies (study 1 and study 2), and for chronic migraine in one study (study 3). All trials were randomized, double-blind, and placebo-controlled. Patients with headache due to medication overuse, or a history of transient ischemic attack, stroke, unstable angina, myocardial infarction, coronary artery bypass surgery, or other revascularization within the previous 12 months of screening were excluded from trials.
Additionally, patients with a history of headache related to opiate overuse were excluded from study 3 of chronic migraine participants. Episodic migraine is defined as 4 to 14 migraine days per month.
Study 1 evaluated erenumab-aooe in 955 participants who received either 70 mg or 140 mg, or placebo over a 6-month period. Study 2 evaluated erenumab-aooe in 577 participants who received either 70 mg or placebo over a 3-month period. Study 3 evaluated the drug in 667 participants with a history of chronic migraine over a 3-month period. Chronic migraine is defined as fifteen or more headache days and eight or more migraine days per month.
In each of the studies, participants were allowed to use acute headache and migraine treatment medications, including NSAIDS, triptans, and ergotamine derivatives. Change in monthly migraine days served as a common efficacy endpoint assessed at 4 to 6 months for study 1, and 3 months for studies 2 and 3. In all trials, groups treated with erenumab-aooe experienced a statistically significant reduction in migraine days (p-value <0.001). In study 1, participants receiving erenumab-aooe experienced reductions of 3.2 and 3.7 migraine days associated with 70 mg and 140 mg of erenumab-aooe respectively, compared to a reduction of 1.8 days in the placebo group. In study 2, participants receiving 70 mg of erenumab-aooe had 2.9 fewer migraine days compared to the 1.8-day reduction seen in the placebo group. Chronic migraine sufferers in both treatment groups of study 3 had 6.6 fewer migraine days compared with the 4.2 fewer migraine days associated with the placebo group.
Injection site reactions and constipation were the most common adverse reactions in clinical trials with greater frequency than placebo. The most common injection site reactions were pain, redness, and itching. It is possible for patients to develop anti-erenumab-aooe antibodies, which could neutralize its pharmacologic activity. Some participants in the studies demonstrated neutralizing antibody production.
Erenumab-aooe is approved for use as once-monthly subcutaneous injections of 70 mg or 140 mg. The drug is available as a 70-mg preservative-free prefilled syringe and an autoinjector. A 140-mg dose of erenumab-aooe is administered as two consecutive 70-mg subcutaneous injections. Store the product in its original packaging to protect it from light, and refrigerate before use. The drug may be stored at room temperature for up to seven days. After seven days at room temperature, the product should be discarded.
1. Aimovig [package insert]. Thousand Oaks, CA: Amgen Inc. May 2018
2. Giamberardino MA, Affiatati G, Costantini R, et al. Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: Current evidence and safety profile of erenumab. J Pain Res. 2017;10: 2751-2760.