Erenumab (Aimovig), a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, has received Health Canada approval for the prevention of migraine in adults who have at least four migraine days per month. This would include patients with episodic (< 15 headache days/month) and chronic migraine (>15 headache days/month, of which >8 are migrainous). The drug is administered by subcutaneous injection once a month. The recommended dose is 70 mg (one injection) per month. Some patients may benefit from a dose of 140 mg qmonthly, administered as two consecutive 70-mg injections. The drug is provided in an autoinjector for patients to self-administer.
Approval of erenumab was based on the results of two randomized controlled studies in chronic and episodic migraine. In a 12-week trial in chronic migraine, the number of monthly migraine days (MMD) was reduced -6.64 days with erenumab 70 mg and -6.63 with erenumab 140 mg (treatment effect vs. placebo -2.46 and -2.45 days, respectively) at month three. The proportion of patients with >50% reduction in MMD was 39.9% with the 70-mg dose and 41.2% with the 140-mg dose (vs. 23.5% with placebo).
In the STRIVE 24-week phase III trial in episodic migraine, the mean change in MMD from baseline to months 4-6 was -3.23 and -3.67 days with the erenumab 70-mg and 140-mg doses compared with -1.83 days with placebo. The proportion of patients with >50% reduction in MMD was 43.3% with the 70-mg dose and 50.0% with the 140-mg dose (vs. 26.6% with placebo) in months 4-6. In both chronic and episodic migraine, a treatment effect was seen as early as month 1.
Erenumab is well-tolerated. In the pivotal trials, the most common adverse events were injection site reactions (70 mg, 5.6%; 140 mg, 4.5%; placebo, 3.2%), constipation (1.3% and 3.2% vs. placebo 1.1%), muscle spasm (0.1% and 2.0% vs. placebo 0.4%), and pruritus (0.7% and 1.8% vs. placebo 0.5%). Use of erenumab should be avoided during pregnancy; caution is advised in women who are breast-feeding.
The median time to peak serum concentration of erenumab is 4-6 days. The pharmacokinetics do not appear to be affected by age, sex or ethnicity. Erenumab is not metabolized by cytochrome P450 enzymes and has a low potential for drug-drug interactions. Coadministration of erenumab and sumatriptan does not appear to affect the pharmacokinetics of sumatriptan; concomitant treatment had no effect on resting blood pressure compared to sumatriptan alone. In clinical trials, the incidence of anti-erenumab antibodies was 6.3% with the 70-mg dose and 2.6% with the 140-mg dose. The development of anti-drug antibodies did not appear to affect the efficacy or safety of erenumab.
Erenumab must be refrigerated. The drug remains stable for up to 14 days at room temperature. The drug should be removed from the refrigerator and kept at room temperature for at least 30 minutes prior to use. Patients should be counselled to inject the abdomen, thigh or upper arm and to rotate injection sites.
For more information see:
Targeting CGRP in migraine, NeuroSens, March 28, 2018
Update on CGRP inhibitors in migraine, NeuroSens, May 18, 2018
Inhibiting CGRP in migraine prophylaxis, NeuroSens, July 25, 2018