An analysis of the attrition of drug candidates from four major pharmaceutical companies
An analysis of the attrition of drug candidates from four major pharmaceutical companies
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DOI：
10.1038/nrd4609
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发表时间：
2015-07-01
影响因子：
120.1
通讯作者：
Weir, Alex
中科院分区：
文献类型：
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作者：
Waring, Michael J.;Arrowsmith, John;Weir, Alex
制药行业仍然面临着解决药物开发中高流失率的巨大压力。由于各个公司的数据集规模有限，通过分析小分子候选药物理化特性的可能联系来减少与功效和安全相关的失败数量的尝试尚未得出结论。在这里，我们描述了阿斯利康、礼来公司、葛兰素史克和辉瑞候选药物消耗的综合数据的汇编和分析。该分析重申，在化合物优化过程中控制理化性质有利于识别候选药物质量的化合物，并首次表明化合物的理化性质与由于安全问题导致的临床失败之间的联系。结果还表明，进一步控制物理化学特性不太可能对损耗率产生显着影响，并且需要进行额外的工作来解决与安全相关的故障。进一步的跨公司合作对于该领域的未来进展至关重要。
The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy-and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.