Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine

被引：10

作者：

Martinez, James M. ^{[1
]}

Hindiyeh, Nada ^{[2
]}

Anglin, Greg ^{[3
]}

Kalidas, Kavita ^{[4
]}

Hodsdon, Michael E. ^{[1
]}

Kielbasa, William ^{[1
]}

Moser, Brian A. ^{[1
]}

Pearlman, Eric M. ^{[1
]}

Garces, Sandra ^{[1
]}

机构：

[1] Eli Lilly & Co, Indianapolis, IN 46285 USA

[2] Stanford Univ, Palo Alto, CA 94304 USA

[3] EIi Lilly Canada Inc, Toronto, ON, Canada

[4] Univ S Florida, Tampa, FL 33620 USA

来源：

CEPHALALGIA | 2020年 / 40卷 / 09期

关键词：

Calcitonin gene-related peptide; anti-drug antibodies; immunogenicity; monoclonal antibodies; galcanezumab; ANTI-DRUG ANTIBODY; THERAPEUTIC ANTIBODIES; ASSAY; RECOMMENDATIONS; DISEASES; TARGETS;

D O I：

10.1177/0333102420920642

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：978 / 989

页数：12

共 30 条

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