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.

中文翻译：

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对发作性或慢性偏头痛患者进行 galcanezumab 3 期试验的免疫原性评估。

背景

该分析表征了 galcanezumab 的免疫原性特征，这是一种在偏头痛 3 期试验中选择性结合降钙素基因相关肽并抑制其活性的人源化单克隆抗体。

方法

对 3 个月慢性偏头痛研究 REGAIN、6 个月发作性偏头痛研究 EVOLVE-1 和 EVOLVE-2 的基线和双盲、安慰剂对照阶段以及基线和开放标签阶段的免疫原性数据进行了分析。 12 个月慢性和偶发性偏头痛研究 CGAJ。评估了基线抗药抗体、治疗中出现的抗药抗体、中和抗药抗体的发生率以及抗药抗体滴度对药代动力学和药效学的影响。使用每月偏头痛天数的平均变化来探讨抗药抗体状态与疗效之间的关系。安全性分析评估了治疗中出现的抗药抗体与超敏反应事件或与注射部位相关的不良事件之间的潜在关系。

发现

在所有研究中，5.9-11.2% 的患者具有基线抗药抗体。在 galcanezumab 组和安慰剂组中，治疗中出现的抗药抗体的发生率为 2.6-12.4% 和 0.5-1.7%。大多数治疗时出现的抗药抗体是在第一次研究药物给药后大约 3-6 个月检测到的。总体而言，观察到的抗药抗体滴度不影响 galcanezumab 浓度、降钙素基因相关肽浓度或 galcanezumab 疗效。没有证据表明与注射部位相关的过敏事件或不良事件是由治疗中出现的抗药抗体介导的。

解释

这些数据表明，免疫原性不影响 galcanezumab 浓度、降钙素基因相关肽浓度或 galcanezumab 在偏头痛患者中的疗效和超敏性特征。