Population Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, Following Subcutaneous Dosing to Healthy Individuals and Patients With Migraine

J Clin Pharmacol. 2020 Feb;60(2):229-239. doi: 10.1002/jcph.1511. Epub 2019 Sep 4.

Abstract

Galcanezumab is a humanized immunoglobulin G (IgG) monoclonal antibody (mAb) indicated for the prevention of migraine that binds to calcitonin gene-related peptide. A population pharmacokinetic (PK) analysis was performed to characterize galcanezumab PK using data pooled from 7 clinical studies. Clinical studies included healthy individuals and patients with episodic or chronic migraine who were administered between 5 and 300 mg galcanezumab. The PK data were analyzed using nonlinear mixed-effects modeling. Galcanezumab concentration-time data were described with a 1-compartment model with first-order absorption following subcutaneous administration and linear elimination. At the median body weight of 74 kg, the estimated population apparent clearance (CL/F) was 0.00785 L/h (34% IIV), the apparent volume of distribution was 7.33 L (34% IIV), and half-life was 27 days. Patient body weight was found to have a modest effect of CL/F, with median galcanezumab concentrations being lower in the heaviest patients compared to the lightest patients, but this outcome was determined not to be clinically relevant in the context of model-estimated random variability. Dosing adjusted for body weight is not warranted in adults. Age, sex, race/ethnicity, immunogenicity, renal/hepatic markers, and injection-site location did not affect galcanezumab PK. In conclusion, galcanezumab exhibits PK parameters typical for an IgG mAb administered subcutaneously. The population PK model developed in this study demonstrates that galcanezumab exhibits linear PK that was not influenced in a clinically relevant manner by the patient factors evaluated.

Trial registration: ClinicalTrials.gov NCT02104765 NCT02576951 NCT02163993 NCT02614196 NCT02614261 NCT02614183 NCT02614287.

Keywords: calcitonin gene-related peptide; galcanezumab; migraine; pharmacokinetics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Calcitonin Gene-Related Peptide / immunology
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Administration Schedule
  • Female
  • Healthy Volunteers
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Migraine Disorders / drug therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • galcanezumab
  • Calcitonin Gene-Related Peptide

Associated data

  • ClinicalTrials.gov/NCT02104765
  • ClinicalTrials.gov/NCT02576951
  • ClinicalTrials.gov/NCT02163993
  • ClinicalTrials.gov/NCT02614196
  • ClinicalTrials.gov/NCT02614261
  • ClinicalTrials.gov/NCT02614183
  • ClinicalTrials.gov/NCT02614287