Stockklausner Clemens, Lampert Anette, Hoffmann Georg F, Ries Markus
Department of Pediatric Hematology, Oncology, and Immunology, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany Cooperation Unit Clinical Pharmacy, Heidelberg University Hospital, Heidelberg, Germany.
Oncologist. 2016 Apr;21(4):487-93. doi: 10.1634/theoncologist.2015-0397. Epub 2016 Mar 28.
Rare cancers are a heterogeneous group of conditions with highly unmet medical needs. Although infrequent in individuals, rare cancers affect millions of people who deserve effective treatments. Therefore, we systematically analyzed the impact of the U.S. Orphan Drug Act of 1983 on delivery of novel treatments for rare cancers.
Quantitative cross-sectional analysis was conducted on the U.S. Food and Drug Administration Orphan Drug Product database according to Strengthening the Reporting of Observational Studies in Epidemiology Statement criteria between 1983 and 2015.
Since 1983, a total of 177 approvals have originated from 1,391 orphan drug designations to treat rare cancers, which represents 36% of all approvals within the U.S. orphan drug act (n = 492). Two compounds (1%) to treat rare cancer were withdrawn after approval. Median time from designation to approval was 2.49 years (interquartile range 1.13-4.64) and decreased significantly over time (p < .001, linear regression). Over the last decade, rare cancer treatments have been transformed from nonspecific cytotoxic agents toward targeted therapies, such as protein kinase inhibitors and monoclonal antibodies, representing the largest groups of innovative rare cancer treatments today. Most compounds were approved to treat solid tumors and hematological malignancies.
The U.S. Orphan Drug Act and associated incentives, such as 7 years of marketing exclusivity, have fostered delivery of novel treatments for rare cancers. More than one-third of all orphan drug approvals address needs of patients suffering from rare cancers. Over the last decade, the understanding of tumorigenesis and genetic driver mutations in different tumor entities has produced innovative treatments, of which many were first approved within the U.S. Orphan Drug Act.
Over the last 30 years, the U.S. Orphan Drug Act successfully delivered numerous novel treatments for rare cancers, of which some were subsequently used in other, nonorphan indications. The understanding of molecular mechanisms of diseases is directly connected to the search for novel therapies. The constant pursuit to translate basic research findings into clinical practice is a crucial prerequisite to address unmet medical needs in rare cancers, as in other rare diseases. Oncological drug development proves to be a major player in overall orphan drug research, displayed by more than one-third of all U.S. Food and Drug Administration-approved orphan drugs with oncological indications.
罕见癌症是一组具有高度未满足医疗需求的异质性疾病。尽管在个体中发病率较低，但罕见癌症影响着数百万需要有效治疗的人群。因此，我们系统分析了1983年美国《孤儿药法案》对罕见癌症新疗法交付的影响。
根据加强流行病学观察性研究报告声明标准，于1983年至2015年期间对美国食品药品监督管理局孤儿药产品数据库进行定量横断面分析。
自1983年以来，共有177项批准源自1391个用于治疗罕见癌症的孤儿药指定，占美国《孤儿药法案》所有批准的36%（n = 492）。两种用于治疗罕见癌症的化合物（1%）在批准后被撤回。从指定到批准的中位时间为2.49年（四分位间距1.13 - 4.64），且随时间显著缩短（p <.001，线性回归）。在过去十年中，罕见癌症治疗已从非特异性细胞毒性药物转向靶向疗法，如蛋白激酶抑制剂和单克隆抗体，它们是当今创新型罕见癌症治疗的最大类别。大多数化合物被批准用于治疗实体瘤和血液系统恶性肿瘤。
美国《孤儿药法案》及相关激励措施，如7年的市场独占权，促进了罕见癌症新疗法的交付。所有孤儿药批准中超过三分之一满足了罕见癌症患者的需求。在过去十年中，对不同肿瘤实体中肿瘤发生和基因驱动突变的认识催生了创新疗法，其中许多首次在美国《孤儿药法案》下获得批准。
在过去30年里，美国《孤儿药法案》成功为罕见癌症提供了众多新疗法，其中一些随后被用于其他非孤儿适应症。对疾病分子机制的理解直接关系到新型疗法的探索。持续致力于将基础研究成果转化为临床实践是满足罕见癌症（如同其他罕见疾病）未满足医疗需求的关键前提。肿瘤药物研发被证明是整个孤儿药研究的主要力量，美国食品药品监督管理局批准的所有有肿瘤适应症的孤儿药中超过三分之一体现了这一点。
