Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies

Abstract

Background: Maintenance of effect following treatment with galcanezumab compared to placebo in adult patients with episodic or chronic migraine was evaluated.

Methods: In 2 similarly designed studies of patients with episodic migraine (6 months) and 1 study of patients with chronic migraine (3 months), patients randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120 mg/month (after an initial loading dose of 240 mg) or 240 mg/month or placebo. Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of 30, 50, 75, and 100% response (defined as ≥30, ≥50, ≥75, and 100% reduction from baseline in monthly migraine headache days [MHD]) at an individual patient level. Logistic regression analyses were used for between treatment comparisons.

Results: A total of 1773 adult patients with episodic migraine (n = 444 for galcanezumab 120 mg; n = 435 for galcanezumab 240 mg; n = 894 for placebo for 2 studies pooled) and 1113 patients with chronic migraine (n = 278 for galcanezumab 120 mg; n = 277 for galcanezumab 240 mg; n = 558 for placebo) were evaluated. In patients with episodic migraine, ≥50% response was maintained in 41.5 and 41.1% of galcanezumab-treated patients (120 mg and 240 mg, respectively) for ≥3 consecutive months (until patient's endpoint) and 19.0 and 20.5%, respectively, for 6 consecutive months and was significantly greater than the 21.4 and 8.0% of placebo-treated patients at ≥3 and 6 months consecutively (P < 0.001). Approximately 6% of galcanezumab-treated patients maintained ≥75% response all 6 months versus 2% of placebo-treated patients. Few galcanezumab-treated patients maintained 100% response. In patients with chronic migraine, 29% of galcanezumab-treated patients maintained ≥30% response all 3 months compared to 16% of placebo patients while ≥50% response was maintained in 16.8 and 14.6% of galcanezumab-treated patients (120 mg and 240 mg) and was greater than placebo (6.3%; p < 0.001). Few patients maintained ≥75% response.

Conclusions: Treatment with galcanezumab 120 mg or 240 mg demonstrated statistically significant and clinically meaningful persistence of effect in patients with episodic migraine (≥3 and 6 consecutive months) and in patients with chronic migraine (for 3 months).

Study identification and trial registration: Study Identification: EVOLVE-1 (I5Q-MC-CGAG); EVOLVE-2 (I5Q-MC-CGAH); REGAIN (I5Q-MC-CGAI) TRIAL REGISTRATION: ClinicalTrials.gov ; NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).

Keywords: Galcanezumab; Maintenance; Migraine; Persistence; Preventive.

Conflict of interest statement

Stefanie Förderreuther, MD Steffi.Foerderreuther@med.uni-muenchen.de

Ludwig-Maximilians-University of Munich, Department of Neurology

Speaker’s Bureau: Novartis, Sanofi

Consultation: Sanofi

Honoraria: Allergan, Hormosan Pharma, AstraZeneca

Advisory Boards: Novartis, Eli Lilly

Qi Zhang, PhD qi.zhang@sanofi.com

Employee of Sanofi, Bridgewater, NJ, USA

Former employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA

Virginia L. Stauffer, PharmD vstauffer@lilly.com

Employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA

Sheena K. Aurora, MD sheena.aurora@lilly.com

Employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA

Miguel JA Láinez, MD, PhD miguel.lainez@sen.es

Hospital Clínico Universitario, Universidad Católica de Valencia, Spain

Research Grants: Allergan, Amgen, ATI, Bayer, Boehringer, electroCore, Eli Lilly, Medtronic, Novartis, Otsuka, Roche, Teva and UCB

Consultation: Allergan, Amgen, ATI, Bayer, Boehringer, electroCore, Eli Lilly, Medtronic, Novartis, Otsuka, Roche, Teva and UCB

Honoraria: Allergan, Amgen, ATI, Bayer, Boehringer, electroCore, Eli Lilly, Medtronic, Novartis, Otsuka, Roche, Teva and UCB

Figures

Fig. 1

Episodic migraine: proportions of patients with maintenance of ≥ 50% response for ≥ 3 consecutive months until patient’s endpoint and response from month 1 to month 6. a maintenance of ≥ 50% response for ≥ 3 consecutive months. b maintenance of ≥ 50% response from month 1 to month 6. Abbreviations: OR = odds ratio. *** = p < 0.001

Fig. 2

Chronic migraine: proportions of patients with maintenance of ≥ 50% response for 3 consecutive months. Abbreviations: OR = odds ratio. *** = p < 0.001

Fig. 3

Cumulative maintained ≥ 50% response: percentages of patients with episodic migraine who reached ≥ 50% response at or before each month and all subsequent months

Fig. 4

Cumulative maintained ≥ 50% response: percentages of patients with chronic migraine who reached ≥ 50% response at or before each month and all subsequent months