BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is important in 
migraine pathophysiology. We assessed the efficacy and safety of erenumab, a 
fully human monoclonal antibody against the CGRP receptor, in patients with 
chronic migraine.
METHODS: This was a phase 2, randomised, double-blind, placebo-controlled, 
multicentre study of erenumab for adults aged 18-65 years with chronic migraine, 
enrolled from 69 headache and clinical research centres in North America and 
Europe. Chronic migraine was defined as 15 or more headache days per month, of 
which eight or more were migraine days. Patients were randomly assigned (3:2:2) 
to subcutaneous placebo, erenumab 70 mg, or erenumab 140 mg, given every 4 weeks 
for 12 weeks. Randomisation was centrally executed using an interactive voice or 
web response system. Patients, study investigators, and study sponsor personnel 
were masked to treatment assignment. The primary endpoint was the change in 
monthly migraine days from baseline to the last 4 weeks of double-blind 
treatment (weeks 9-12). Safety endpoints were adverse events, clinical 
laboratory values, vital signs, and anti-erenumab antibodies. The efficacy 
analysis set included patients who received at least one dose of investigational 
product and completed at least one post-baseline monthly measurement. The safety 
analysis set included patients who received at least one dose of investigational 
product. The study is registered with ClinicalTrials.gov, number NCT02066415.
FINDINGS: From April 3, 2014, to Dec 4, 2015, 667 patients were randomly 
assigned to receive placebo (n=286), erenumab 70 mg (n=191), or erenumab 140 mg 
(n=190). Erenumab 70 mg and 140 mg reduced monthly migraine days versus placebo 
(both doses -6·6 days vs placebo -4·2 days; difference -2·5, 95% CI -3·5 to 
-1·4, p<0·0001). Adverse events were reported in 110 (39%) of 282 patients, 83 
(44%) of 190 patients, and 88 (47%) of 188 patients in the placebo, 70 mg, and 
140 mg groups, respectively. The most frequent adverse events were 
injection-site pain, upper respiratory tract infection, and nausea. Serious 
adverse events were reported by seven (2%), six (3%), and two (1%) patients, 
respectively; none were reported in more than one patient in any group or led to 
discontinuation. 11 patients in the 70 mg group and three in the 140 mg group 
had anti-erenumab binding antibodies; none had anti-erenumab neutralising 
antibodies. No clinically significant abnormalities in vital signs, laboratory 
results, or electrocardiogram findings were identified. Of 667 patients randomly 
assigned to treatment, 637 completed treatment. Four withdrew because of adverse 
events, two each in the placebo and 140 mg groups.
INTERPRETATION: In patients with chronic migraine, erenumab 70 mg and 140 mg 
reduced the number of monthly migraine days with a safety profile similar to 
placebo, providing evidence that erenumab could be a potential therapy for 
migraine prevention. Further research is needed to understand long-term efficacy 
and safety of erenumab, and the applicability of this study to real-world 
settings.
FUNDING: Amgen.