BACKGROUND: Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin 
gene-related peptide (CGRP) and is indicated for the preventive treatment of 
migraine. Galcanezumab demonstrated early onset of effect in patients with 
migraine but it is unknown whether the same holds true for patients who have not 
benefited from multiple prior migraine preventives.
METHODS: Patients with episodic or chronic migraine from a 3-month, randomized, 
double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 
migraine preventive medication category failures in the past 10 years were 
randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading 
dose; N = 232). In this post-hoc analysis, change from baseline in number of 
monthly and weekly migraine headache days was assessed. Monthly onset of effect 
was the earliest month at which significant improvement with galcanezumab 
compared to placebo was achieved and maintained at all subsequent months. Weekly 
onset was the initial week at which statistical separation was achieved and 
maintained at all subsequent weeks during that month. Proportion of patients 
with migraine headache days in the first week of treatment, and patients 
achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.
RESULTS: Galcanezumab-treated patients had a significantly greater reduction in 
monthly migraine headache days starting at month 1, which remained significant 
for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean 
change from baseline: placebo - 0.7; galcanezumab - 4.0). Weekly migraine 
headache days was significantly reduced in galcanezumab-treated patients 
starting at week 1 and continued for each subsequent week of month 1 compared to 
placebo (all p < 0.01, week 1 mean change from baseline: placebo - 0.2; 
galcanezumab - 1.1). A significantly smaller percentage of patients had a 
migraine headache on the first day after galcanezumab treatment compared to 
placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all 
p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, 
≥75%, and 100% response at months 1-3 (all p < 0.05) and at weeks 1-4 of month 1 
compared to placebo (all p < 0.01).
CONCLUSION: Galcanezumab showed early onset of effect beginning the day after 
treatment initiation in patients who had not previously benefited from migraine 
preventive treatments.
TRIAL REGISTRATION: ClinicalTrials.gov , NCT03559257 . Registered 18 June 2018.