BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin 
gene-related peptide (CGRP), is being investigated as a preventive treatment for 
migraine. We compared two fremanezumab dose regimens with placebo for the 
prevention of chronic migraine.
METHODS: In this phase 3 trial, we randomly assigned patients with chronic 
migraine (defined as headache of any duration or severity on ≥15 days per month 
and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab 
quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), 
fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or 
matching placebo. Both fremanezumab and placebo were administered by means of 
subcutaneous injection. The primary end point was the mean change from baseline 
in the average number of headache days (defined as days in which headache pain 
lasted ≥4 consecutive hours and had a peak severity of at least a moderate level 
or days in which acute migraine-specific medication [triptans or ergots] was 
used to treat a headache of any severity or duration) per month during the 12 
weeks after the first dose.
RESULTS: Of 1130 patients enrolled, 376 were randomly assigned to fremanezumab 
quarterly, 379 to fremanezumab monthly, and 375 to placebo. The mean number of 
baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, 
respectively. The least-squares mean (±SE) reduction in the average number of 
headache days per month was 4.3±0.3 with fremanezumab quarterly, 4.6±0.3 with 
fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons 
with placebo). The percentage of patients with a reduction of at least 50% in 
the average number of headache days per month was 38% in the 
fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in 
the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of 
hepatic function occurred in 5 patients in each fremanezumab group (1%) and 3 
patients in the placebo group (<1%).
CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine 
resulted in a lower frequency of headache than placebo in this 12-week trial. 
Injection-site reactions to the drug were common. The long-term durability and 
safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals; 
ClinicalTrials.gov number, NCT02621931 .).