Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures

Abstract

Background: Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives.

Methods: Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.

Results: Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo - 0.7; galcanezumab - 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo - 0.2; galcanezumab - 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1-3 (all p < 0.05) and at weeks 1-4 of month 1 compared to placebo (all p < 0.01).

Conclusion: Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments.

Trial registration: ClinicalTrials.gov , NCT03559257 . Registered 18 June 2018.

Keywords: CGRP; Calcitonin gene-related peptide; Early onset; Galcanezumab; Migraine; Preventive failure.

Conflict of interest statement

Within the last two years, TJS has received personal compensation for consulting with Alder, Allergan, Amgen, Biohaven, Cipla, Click Therapeutics, Eli Lilly and Company, Equinox, Lundbeck, Novartis, XoC Pharmaceuticals, and Weber and Weber. He has stock options in Aural Analytics and Nocira and has received a research grant from Amgen. He received royalties from UpToDate.

DKK, YD, LYM, and EP are full-time employees of Eli Lilly and Company and/or minor stockholders of the sponsor of the work, Eli Lilly and Company.

KS has received compensation from Biogen, Genentech, Sanofi-Genzyme, Eli Lilly and Company, Teva, Novartis, Amgen, Biohaven, and Allergan.

Figures

Fig. 1

LS mean change from baseline in number of monthly migraine headache days. *** p ≤ 0.0001 vs placebo. LS least-squares. SE standard error

Fig. 2

LS mean change from baseline in number of weekly migraine headache days. ** p < 0.01, *** p ≤ 0.0001 vs placebo. LS least-squares. SE standard error. Dotted line separates month 1, which was used in the onset analysis, from remaining months

Fig. 3

Estimated proportion of patients with a migraine headache on each day of the first week after the first injection in month 1. * p < 0.05, ** p < 0.01, *** p ≤ 0.0001 vs placebo. SE standard error

Fig. 4

Estimated mean percentage of patients with ≥50%, ≥75%, and 100% reduction from baseline in monthly migraine headache days at months 1–3. * p < 0.05, ** p < 0.01, *** p ≤ 0.0001 vs placebo. SE standard error

Fig. 5

Estimated mean percentage of patients with ≥50%, ≥75%, and 100% reduction from baseline in weekly migraine headache days at weeks 1–4 of month 1. ** p < 0.01, *** p ≤ 0.0001 vs placebo. SE standard error