Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study

Abstract

Background: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia.

Methods: This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.

Results: In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo).

Conclusions: Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia.

Trial registration: ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.

Keywords: Calcitonin gene-related peptide; Episodic migraine; Galcanezumab; Humanized monoclonal antibody.

Conflict of interest statement

JZ is a full-time employee of Eli Lily and Company. SY serves as associated editor of the Journal of Headache and Pain and as a member of the International Headache Society. ZJ has no competing interests. BH, GL, XL, SW, TY, XL, HZ, and SY declare receiving clinical research fees from Eli Lilly and Company for participating as investigators in the PERSIST study.

© 2022. The Author(s).

Figures

Fig. 1

Study design. aEligibility period determined between a minimum of 30 days and a maximum of 40 days. bPatients randomized to galcanezumab 120 mg received a loading dose of 240 mg at the first injection only (Visit 3). cTelephone visits. dAt Visit 7, patients randomized to placebo who entered the open-label extension received galcanezumab at a loading dose of 240 mg, while patients randomized to galcanezumab 120 mg continued treatment at the 120 mg dose. SP, study period; X indicates when dosing occurred

Fig. 2

Patient disposition

Fig. 3

a Overall LS mean change from month 1 to 3 in monthly migraine headache days; b LS mean change at month 1 to 3 in monthly migraine headache days LS, least squares; SE, standard error. ***p < 0.0001 versus placebo

Fig. 4

Key secondary endpoints: a mean percentage of patients with ≥ 50%, ≥ 75%, and 100% reductions in monthly migraine headache days; b LS mean change in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive CI, confidence interval; LS, least squares; SE, standard error. ***p < 0.0001 versus placebo