Williams Robert
Drug Development Office, Cancer Research UK , Angel Building, 407 St John Street, London EC1V 4AD , UK +44 203 469 6900 ;
Expert Opin Investig Drugs. 2015 Jan;24(1):95-110. doi: 10.1517/13543784.2015.971154. Epub 2014 Oct 14.
Introduction: Attrition in clinical development is widely recognised as a key factor negatively impacting overall R&D efficiency. Gaining an understanding of the reasons for candidate failure may lead to improvements in success rates and return on R&D investment. Areas covered: This report provides an analysis of reasons for discontinuation of development of 40 drugs dropped from the global oncology pipeline in 2013 - the largest number of terminations reported since this annual analysis began in 2005. The article also provides discussion on the observations in the context of contemporary views of anticancer drug development. Expert opinion: Twelve drugs (30% of the 2013 discontinuations) failed in Phase III development. None of the pivotal trials investigating these agents incorporated molecular biomarkers for patient stratification. The largest number of drug terminations (20 out of 40) occurred in Phase I development with reasons for termination commonly reported as strategic or undisclosed. Raising the bar in terms of requirements for progression from preclinical development, including the identification of robust pharmacodynamic biomarkers and biomarkers potentially predictive of clinical benefit may lead to an increase in success rates in clinical development and of overall R&D efficiency.
临床开发中的药物损耗被广泛认为是对整体研发效率产生负面影响的关键因素。了解候选药物失败的原因可能会提高成功率和研发投资回报率。
本报告分析了2013年从全球肿瘤学研发管线中剔除的40种药物的开发终止原因——这是自2005年开始此项年度分析以来报告的终止数量最多的一次。本文还结合当代抗癌药物开发观点对这些观察结果进行了讨论。
12种药物（占2013年终止药物的30%）在III期开发中失败。调查这些药物的关键试验均未纳入用于患者分层的分子生物标志物。40种药物中终止数量最多的（40种中的20种）发生在I期开发，终止原因通常报告为战略原因或未披露。提高临床前开发进展的要求标准，包括识别强大的药效学生物标志物和可能预测临床获益的生物标志物，可能会提高临床开发的成功率和整体研发效率。
