Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20903, USA.
J Pharm Sci. 2023 Sep;112(9):2313-2320. doi: 10.1016/j.xphs.2023.06.019. Epub 2023 Jul 6.
Though hundreds of drugs have been approved by the US Food and Drug Administration (FDA) for treating various rare diseases, most rare diseases still lack FDA-approved therapeutics. To identify the opportunities for developing therapies for these diseases, the challenges of demonstrating the efficacy and safety of a drug for treating a rare disease are highlighted herein. Quantitative systems pharmacology (QSP) has increasingly been used to inform drug development; our analysis of QSP submissions received by FDA showed that there were 121 submissions as of 2022, for informing rare disease drug development across development phases and therapeutic areas. Examples of published models for inborn errors of metabolism, non-malignant hematological disorders, and hematological malignancies were briefly reviewed to shed light on use of QSP in drug discovery and development for rare diseases. Advances in biomedical research and computational technologies can potentially enable QSP simulation of the natural history of a rare disease in the context of its clinical presentation and genetic heterogeneity. With this function, QSP may be used to conduct in-silico trials to overcome some of the challenges in rare disease drug development. QSP may play an increasingly important role in facilitating development of safe and effective drugs for treating rare diseases with unmet medical needs.
尽管美国食品和药物管理局 (FDA) 已批准数百种药物用于治疗各种罕见疾病，但大多数罕见疾病仍缺乏 FDA 批准的治疗方法。为了确定为这些疾病开发疗法的机会，本文强调了证明治疗罕见疾病的药物的疗效和安全性的挑战。定量系统药理学 (QSP) 已越来越多地用于为药物开发提供信息；我们对 FDA 收到的 QSP 提交进行的分析表明，截至 2022 年，有 121 项提交用于在各个开发阶段和治疗领域为罕见疾病药物开发提供信息。简要回顾了用于代谢性先天缺陷、非恶性血液疾病和血液恶性肿瘤的已发表模型，以阐明 QSP 在罕见疾病药物发现和开发中的应用。生物医学研究和计算技术的进步可以潜在地使 QSP 能够模拟罕见疾病在其临床表现和遗传异质性背景下的自然病史。通过此功能，QSP 可用于进行计算机模拟试验，以克服罕见疾病药物开发中的一些挑战。QSP 可能在促进开发治疗有未满足医疗需求的罕见疾病的安全有效药物方面发挥越来越重要的作用。
