美国迪尔菲尔德管理公司Matthew R. Nelson研究组报道了完善遗传学证据对临床成功的影响。这一研究成果发表在2024年4月17日出版的国际学术期刊《自然》上。

在本研究中，研究人员利用过去十年基因证据的增长，更好地区分药物临床成功与失败的特征。研究估计，有基因支持的药物研发成功概率是没有基因支持药物研发成功率的2.6倍。这一相对成功率因治疗领域和开发阶段而异，并随着对致病基因的了解增加而提高，但基本不受遗传效应大小、等位基因频率或发现年份的影响。

该结果表明，人类对基因功能的了解还远远没有达到顶峰，以达到助力发现更有效药物靶点的水平。

据了解，药物研发的成本主要由研发失败造成，只有约10%的临床项目最终获得批准。根据之前的估计，人类基因证据可将药物从临床研发到批准的成功率提高一倍。

附：英文原文

Title: Refining the impact of genetic evidence on clinical success

Author: Minikel, Eric Vallabh, Painter, Jeffery L., Dong, Coco Chengliang, Nelson, Matthew R.

Issue&Volume: 2024-04-17

Abstract: The cost of drug discovery and development is driven primarily by failure1, with only about 10% of clinical programmes eventually receiving approval2,3,4. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval5. In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency or year of discovery. These results indicate we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.

DOI: 10.1038/s41586-024-07316-0

Source: https://www.nature.com/articles/s41586-024-07316-0