Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments

Abstract

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).

Keywords: CGRP; CGRP mAb; Efficacy; Fail preventive; Galcanezumab; Migraine; Monoclonal antibody; Quality of life.

Conflict of interest statement

DKK, YD, and LYM are full-time employees of Eli Lilly and Company, and/or minor stockholders of the sponsor of the work, Eli Lilly and Company. JT has received compensation from Eli Lilly and Company for speaking and advisory board service, and indirect compensation for work related to clinical trials. SKA is an employee of Impel NeuroPharma. ALG has received compensation from Allergan Canada, Eli Lilly and Company, and Novartis.

Figures

Fig. 1

LS mean change from baseline in the number of monthly migraine headache days in patients who did not benefit from migraine preventive medication due to inadequate efficacy. *p<0.05, **p<0.01, ***p<0.0001 vs placebo. Abbreviations: LS least-squares, N number of intent-to-treat patients, SE standard error

Fig. 2

LS mean change from baseline in the number of monthly migraine headache days in patients who did not benefit from migraine preventive medication due to safety or tolerability. *p<0.05, **p<0.01 vs placebo. aOnly one patient discontinued onabotulinum toxin A due to safety/tolerability reasons; therefore, no statistical analyses were performed. Change from baseline showed a numerical reduction in monthly migraine headache days. Abbreviations: LS least-squares, N number of intent-to-treat patients, SE standard error