BACKGROUND: Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal 
antibody (mAb) indicated for the preventive treatment of migraine. While 
galcanezumab has demonstrated efficacy in patients who did not respond to prior 
preventive medications in general, its efficacy in patients who did not benefit 
from individual, commonly prescribed preventive treatments due to inadequate 
efficacy or safety/tolerability remains unknown.
METHODS: CONQUER was a 3-month, randomized, double-blind, placebo-controlled, 
phase 3b study that enrolled patients with episodic or chronic migraine who had 
2 to 4 migraine preventive medication category failures in the past 10 years. 
Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 
120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to 
determine the efficacy of galcanezumab in patients who had not benefited from 
six of the most commonly prescribed migraine preventive medications. The mean 
change from baseline in monthly migraine headache days and ≥ 50 % response rates 
were assessed over months 1-3. Improvement in Migraine-Specific Questionnaire 
Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The 
endpoints were estimated via mixed model with repeated measures.
RESULTS: The most common treatment failures due to inadequate efficacy or 
safety/tolerability, which at least 20 % of patients reported trying without 
benefit, included topiramate, amitriptyline, propranolol, valproate or 
divalproex, onabotulinum toxin A, and metoprolol. Patients who had not 
previously benefited from these treatments had a greater mean reduction in 
monthly migraine headache days across months 1-3 in the galcanezumab group 
compared to placebo (all p < 0.01). More patients treated with galcanezumab 
experienced a ≥ 50 % reduction from baseline in monthly migraine headache days 
across months 1-3 compared to placebo (all p < 0.05). Galcanezumab-treated 
patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to 
placebo (all p < 0.01).
CONCLUSIONS: In this population, galcanezumab was effective in reducing monthly 
migraine headache days, improving response rates, and enhancing quality of life 
in patients who had not previously benefited from topiramate, amitriptyline, 
propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol 
due to inadequate efficacy or safety/tolerability.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03559257 (CONQUER).