对成年人大分子治疗方法的固定剂量与基于体型的剂量方法的重新评估
Andrew B SyBing1, Huili Chen1, Diane D Wang1
1Pfizer Oncology, San Diego, California, USA.
Clinical pharmacology and therapeutics
|August 16, 2025
概括
固定剂量适用于早期试验中的大多数大分子疗法,与之前的建议保持一致. 这种方法提供了诸如方便和减少错误等好处,并得到了身体尺寸对清除效应的新数据的支持.
科学领域:
- 药理动力学和药物开发
- 生物制药剂量策略 生物制药剂量策略
- 临床试验设计 临床试验设计
背景情况:
- 之前的研究在首次在人体 (FIH) 试验中建议大分子疗法的固定剂量.
- 固定的剂量提供了优势,包括方便性,减少医疗错误和成本效益.
- 剂量方法建议是基于身体大小对清除 (α) 值和治疗窗口的影响.
研究的目的:
- 用更大,更多样化的分子数据集重新评估以前的剂量建议.
- 评估大分子治疗药物的固定剂量与基于体型的剂量是否合适.
- 调查FIH剂量和批准的剂量方法之间的关系.
主要方法:
- 对143种不同的大分子疗法数据集的分析.
- 评估身体尺寸对批准药物的清除 (α) 值的影响.
- 固定剂量与基于身体大小的剂量策略的比较.
- 评估FIH剂量方法对最终批准的剂量方法的影响.
主要成果:
- 62%的非抗体-药物-合物 (ADC) 药物被批准使用固定的剂量.
- 58%的非ADC药物被批准以身体大小为基础的剂量具有α<0.7,其中固定的剂量将是合适的.
- 只有16%的非ADC药物需要基于体型的剂量.
- 68%的药物保持了FIH批准的相同剂量方法.
- 在56%的非ADC药物中观察到α与批准剂量之间的关系.
结论:
- 这些发现支持了以前关于在大分子治疗中固定剂量的建议.
- 建议在药物开发过程中使用决策树来指导选择合适的剂量方法.
- 基于人体大小的剂量仅对少数非ADC药物要求.
- 缺乏临床上有意义的暴露差异往往证明了批准的剂量,当α没有解释选择时.
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