罕见肿瘤治疗学:美国食品药品监督管理局对临床药理学药物批准包(2019-2023)的审查、最佳实践和建议。

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Amitava Mitra, Jong Bong Lee, Douglas Steinbach, Anasuya Hazra, Rajesh Krishna
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引用次数: 0

摘要

罕见病药物开发面临许多挑战,罕见肿瘤适应症也没有什么不同。为了了解与临床药理学原理在罕见肿瘤产品开发中的应用有关的监管格局,我们审查了2019年1月至2023年3月期间美国食品药品监督管理局39项批准的公开信息。目的是了解此类批准中预期的临床药理学研究和知识库。还对模型知情药物开发(MIDD)的应用进行了审查,因为这些方法有望在填补罕见肿瘤学的临床药理学空白方面发挥关键作用,在罕见肿瘤学中,临床试验的数量和规模可能会继续很小。研究结果强调了临床药理学如何有助于证明有效性、剂量优化以及阐明影响药物行为的内在和外在因素。临床药理学研究经常与许多NDA/BLA的建模相结合。在收到的上市后需求(PMR)中,18%用于剂量优化,49%用于DDI,8%用于QTc,49%用于特定人群,5%用于食物效果。针对提交的11种生物制品的免疫原性,发布了两项上市后承诺(PMC)。15%(39份中的6份)的提交材料使用最大耐受剂量(MTD)将其分子推进2期研究。其中3项批准获得了用于剂量优化的PMR。3. + 3是最普遍的1期设计,在审查的新药申请(NDA)/生物许可证申请(BLA)中使用了74%。Rest使用了创新方法,如BLRM、BOIN或mTPi,其中BLRM是最常见的。无缝的临床药理学和MIDD方法对于罕见肿瘤药物的开发至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rare oncology therapeutics: review of clinical pharmacology package of drug approvals (2019-2023) by US FDA, best practices and recommendations.

Rare oncology therapeutics: review of clinical pharmacology package of drug approvals (2019-2023) by US FDA, best practices and recommendations.

There are many challenges with rare diseases drug development and rare oncology indications are not different. To understand the regulatory landscape as it relates to application of clinical pharmacology principles in rare oncology product development, we reviewed publicly available information of 39 approvals by US FDA between January 2019 and March 2023. The objective was to understand the expected clinical pharmacology studies and knowledge base in such approvals. Model informed drug development (MIDD) applications were also reviewed, as such approaches are expected to play a critical role in filling clinical pharmacology gaps in rare oncology, where number of clinical trials and size of these trials will perhaps continue to be small. The findings highlighted how clinical pharmacology contributed to the evidence of effectiveness, dose optimization and elucidation of intrinsic and extrinsic factors affecting drug's behavior. Clinical pharmacology studies were often integrated with modeling in many of the NDAs/BLAs. Of the post marketing requirements (PMR) received, 18% were for dose optimization, 49% for DDI, 8% for QTc, 49% for specific population, and 5% for food effect. Two post marketing commitments (PMC) were issued for immunogenicity of the 11 biologics submissions. 15% (6 of 39) of the submissions used maximum tolerated dose (MTD) to advance their molecule into Phase 2 studies. Of them 3 approvals received PMR for dose optimization. 3 + 3 was the most prevalent Phase 1 design with use in 74% of the New Drug Applications (NDA)/Biologic License Applications (BLA) reviewed. Rest used innovative approaches such as BLRM, BOIN or mTPi, with BLRM being the most common. Seamless clinical pharmacology and MIDD approaches are paramount for rare oncology drug development.

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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
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