Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials

Abstract

Introduction: Galcanezumab, a humanized monoclonal antibody that binds to calcitonin gene-related peptide, is approved for the preventive treatment of migraine in adults. It is self-administered once monthly as a subcutaneous injection. This paper describes the time course of effect of galcanezumab in patients with episodic and chronic migraine.

Methods: Data were based on three double-blind, placebo-controlled, phase 3 studies. Patients (1773 episodic and 1113 chronic) were randomized (2:1:1) to monthly doses of placebo, galcanezumab 120 mg with a 240 mg loading dose, or galcanezumab 240 mg (January 2016-March 2017). Onset of effect was determined using a sequential analysis approach based on earliest time point at which galcanezumab achieved and subsequently maintained statistical superiority to placebo. Maintenance of effect was a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of at least 50% response at the individual patient level. Cessation of effect was determined during a 4-month post-treatment period on the basis of change from baseline in monthly migraine headache days.

Results: Galcanezumab led to a lower percentage of patients who had a migraine headache on the first day after injection, provided maintenance of effect throughout the duration of the double-blind treatment period, and gradually lost effect without signs of rebound headache throughout the post-treatment period in most patients with episodic and chronic migraine.

Conclusion: Galcanezumab is a novel preventive therapeutic option for adult patients with migraine that has early onset of action, maintenance of effect, and gradual reduction of effect upon treatment cessation.

Trial registration: ClinicalTrials.gov: NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).

Keywords: CGRP antagonist; Cessation; Galcanezumab; Maintenance; Migraine; Migraine prevention; Onset.

Fig. 1

Onset and cessation of effect by month: a LS mean change from baseline in monthly migraine headache days in the treatment and post-treatment periods of EVOLVE-1, b EVOLVE-2, and c REGAIN. **P < 0.01; ***P < 0.001 vs placebo. ^aPatients who entered the open-label extension period of REGAIN received a 240 mg loading dose of GMB (at month 3), followed by a maintenance dose of 120 mg/month at the next month (month 4), with flexible dosing thereafter throughout the open-label extension (120 or 240 mg/month). Treatment assignment is based on the double-blind treatment phase. GMB galcanezumab, LS least squares, OLE open-label extension, SE standard error. Reprinted with permission from [20]

Fig. 2

Onset of effect by week: a LS mean change from 7-day baseline in weekly migraine headache days for weeks 1–4 of month 1 for EVOLVE-1, b EVOLVE-2, and c REGAIN. *P < 0.05; ***P < 0.001 vs placebo. ^⌖Onset of effect analyses evaluated pooled GMB-treated patients vs placebo (as both GMB groups received 240 mg in the first month). GMB galcanezumab, LS least squares, SE standard error

Fig. 3

Onset of effect by day: a Daily estimated proportions of patients with migraine headache days in week 1 of month 1 for EVOLVE-1, b EVOLVE-2, and c REGAIN. *P < 0.05; **P < 0.01; ***P < 0.001 vs placebo. ^⌖Onset of effect analyses evaluated pooled GMB-treated patients vs placebo (as both GMB groups received 240 mg in the first month). GMB galcanezumab, N number of intent-to-treat patients, SE standard error

Fig. 4

Maintenance of effect: a Percentages of patients with episodic migraine with maintenance of ≥ 50% response for ≥ 3 consecutive months including the patient’s last month of dosing. b Percentages of patients with episodic migraine with maintenance of ≥ 50% response for 6 consecutive months. c Percentages of patients with chronic migraine with maintenance of ≥ 50% response for 3 consecutive months. ***P < 0.001 vs placebo. OR odds ratio. Reprinted with permission from [19]