BACKGROUND: A substantial proportion of patients with migraine does not respond 
to, or cannot tolerate, oral preventive treatments. Erenumab is a novel 
CGRP-receptor antibody with preventive efficacy in migraine. We assessed its 
efficacy and tolerability in patients with episodic migraine in whom previous 
treatment with two-to-four migraine preventives had been unsuccessful.
METHODS: LIBERTY was a 12-week, double-blind, placebo-controlled randomised 
study at 59 sites in 16 countries. Eligible patients were aged 18-65 years and 
had a history of episodic migraine with or without aura for at least 12 months, 
had migraine for an average of 4-14 days per month during the 3 months before 
screening, and had been treated unsuccessfully (in terms of either efficacy or 
tolerability, or both) with between two and four preventive treatments. Eligible 
participants were randomly assigned (1:1) to receive either erenumab 140 mg (via 
two 70 mg injections) or placebo every 4 weeks subcutaneously for 12 weeks. 
Randomisation was by interactive response technology and was stratified by 
monthly frequency of migraine headache (4-7 vs 8-14 migraine days per month) 
during the baseline phase. Cenduit generated the randomisation list and assigned 
participants to groups. Participants, investigators, people doing various 
assessments, and the study sponsor were masked to treatment assignment. The 
primary endpoint was the proportion of patients achieving a 50% or greater 
reduction in the mean number of monthly migraine days during weeks 9-12. 
Efficacy was measured in the full analysis set, which included all randomly 
assigned patients who started their assigned treatment and completed at least 
one post-baseline monthly migraine day measurement. Safety and tolerability were 
assessed by recording adverse events and by physical examination, assessment of 
vital signs, clinical laboratory assessments, and electrocardiography. Safety 
was assessed in all randomly assigned patients who received at least one dose of 
study drug. This trial is registered with ClinicalTrials.gov, number 
NCT03096834. The trial is closed to new participants, but the open-label 
extension phase is ongoing.
FINDINGS: Between March 20, 2017, and Oct 27, 2017, 246 participants were 
randomly assigned, 121 to the erenumab group and 125 to the placebo group. 95 of 
246 (39%) participants had previously unsuccessfully tried two preventive drugs, 
93 (38%) had tried three, and 56 (23%) had tried four. At week 12, 36 (30%) 
patients in the erenumab had a 50% or greater reduction from baseline in the 
mean number of monthly migraine days, compared with 17 (14%) in the placebo 
group (odds ratio 2·7 [95% CI 1·4-5·2]; p=0·002). The tolerability and safety 
profiles of erenumab and placebo were similar. The most frequent 
treatment-emergent adverse event was injection site pain, which occurred in 
seven (6%) participants in both groups.
INTERPRETATION: Compared with placebo, erenumab was efficacious in patients with 
episodic migraine who previously did not respond to or tolerate between two and 
four previous migraine preventive treatments. Erenumab might be an option for 
patients with difficult-to-treat migraine who have high unmet needs and few 
treatment options.
FUNDING: Novartis Pharma.