Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine.
Calcitonin gene-related peptide
anti-drug antibodies
galcanezumab
immunogenicity
monoclonal antibodies
Journal
Cephalalgia : an international journal of headache
ISSN: 1468-2982
Titre abrégé: Cephalalgia
Pays: England
ID NLM: 8200710
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
29
4
2020
medline:
26
10
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
This analysis characterizes the immunogenicity profile of galcanezumab, a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and inhibits its activity, in phase 3 migraine trials. Immunogenicity data were analyzed from baseline and double-blind, placebo-controlled phases of the 3-month chronic migraine study REGAIN, the 6-month episodic migraine studies EVOLVE-1 and EVOLVE-2, and from baseline and open-label phases of the 12-month chronic and episodic migraine Study CGAJ. The incidence of baseline antidrug antibodies, treatment-emergent antidrug antibodies, neutralizing antidrug antibodies, and the effect of antidrug antibody titer on pharmacokinetics and pharmacodynamics were assessed. The relationship between antidrug antibody status and efficacy was explored using average change in monthly migraine headache days. Safety analyses assessed the potential relationship between treatment-emergent antidrug antibodies and hypersensitivity events or adverse events related to injection sites. Across studies, 5.9-11.2% of patients had baseline antidrug antibodies. The incidence of treatment-emergent antidrug antibodies was 2.6-12.4% in the galcanezumab group and 0.5-1.7% in the placebo group. The majority of treatment-emergent antidrug antibodies were detected approximately 3-6 months after first study drug dose. Overall, the observed antidrug antibody titer did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or galcanezumab efficacy. There was no evidence that hypersensitivity events or adverse events related to injection sites were mediated by treatment-emergent antidrug antibodies. These data showed that immunogenicity did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or the efficacy and hypersensitivity profile of galcanezumab in patients with migraine.
Sections du résumé
BACKGROUND
This analysis characterizes the immunogenicity profile of galcanezumab, a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and inhibits its activity, in phase 3 migraine trials.
METHODS
Immunogenicity data were analyzed from baseline and double-blind, placebo-controlled phases of the 3-month chronic migraine study REGAIN, the 6-month episodic migraine studies EVOLVE-1 and EVOLVE-2, and from baseline and open-label phases of the 12-month chronic and episodic migraine Study CGAJ. The incidence of baseline antidrug antibodies, treatment-emergent antidrug antibodies, neutralizing antidrug antibodies, and the effect of antidrug antibody titer on pharmacokinetics and pharmacodynamics were assessed. The relationship between antidrug antibody status and efficacy was explored using average change in monthly migraine headache days. Safety analyses assessed the potential relationship between treatment-emergent antidrug antibodies and hypersensitivity events or adverse events related to injection sites.
FINDINGS
Across studies, 5.9-11.2% of patients had baseline antidrug antibodies. The incidence of treatment-emergent antidrug antibodies was 2.6-12.4% in the galcanezumab group and 0.5-1.7% in the placebo group. The majority of treatment-emergent antidrug antibodies were detected approximately 3-6 months after first study drug dose. Overall, the observed antidrug antibody titer did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or galcanezumab efficacy. There was no evidence that hypersensitivity events or adverse events related to injection sites were mediated by treatment-emergent antidrug antibodies.
INTERPRETATION
These data showed that immunogenicity did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or the efficacy and hypersensitivity profile of galcanezumab in patients with migraine.
Identifiants
pubmed: 32340471
doi: 10.1177/0333102420920642
pmc: PMC7469706
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
galcanezumab
55KHL3P693
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
978-989Références
MAbs. 2010 May-Jun;2(3):256-65
pubmed: 20400861
Autoimmun Rev. 2015 Jul;14(7):569-74
pubmed: 25742758
Adv Drug Deliv Rev. 2017 Dec 1;122:2-19
pubmed: 27916504
AAPS J. 2017 Nov;19(6):1564-1575
pubmed: 29063411
J Allergy Clin Immunol. 2017 Mar;139(3):1035-1037.e6
pubmed: 27717666
Cephalalgia. 2018 Jul;38(8):1442-1454
pubmed: 29848108
Neurology. 2018 Dec 11;91(24):e2211-e2221
pubmed: 30446596
J Invest Dermatol. 2018 Oct;138(10):2168-2173
pubmed: 29751001
J Headache Pain. 2019 Jan 16;20(1):6
pubmed: 30651064
JAMA Neurol. 2018 Sep 1;75(9):1080-1088
pubmed: 29813147
J Clin Pharmacol. 2020 Feb;60(2):229-239
pubmed: 31482569
Bioanalysis. 2010 Dec;2(12):1961-9
pubmed: 21110740
Expert Rev Mol Med. 2011 Nov 29;13:e36
pubmed: 22123247
J Immunol Methods. 2015 Apr;419:1-8
pubmed: 25795420
Ann Rheum Dis. 2014 Jun;73(6):1138-43
pubmed: 23666932
AAPS J. 2013 Jul;15(3):893-6
pubmed: 23761225
Ann Rheum Dis. 2013 Jan;72(1):104-9
pubmed: 22759910
J Pharm Biomed Anal. 2008 Dec 15;48(5):1267-81
pubmed: 18993008
Nat Rev Drug Discov. 2003 Jan;2(1):52-62
pubmed: 12509759
AAPS J. 2013 Jul;15(3):852-5
pubmed: 23620231
Curr Probl Dermatol. 2018;53:37-48
pubmed: 29131036
Cephalalgia. 2018 May;38(6):1015-1025
pubmed: 29310444
J Immunol Methods. 2007 Oct 31;327(1-2):10-7
pubmed: 17716682
Headache. 2015 Sep;55(8):1171-82
pubmed: 26316307
Ann Rheum Dis. 2015 Jan;74(1):311-4
pubmed: 25342759
BMC Neurol. 2018 Nov 9;18(1):188
pubmed: 30413151
Ann Rheum Dis. 2013 Dec;72(12):1947-55
pubmed: 23223420