Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
JiveCast, Raleigh, NC, USA.
Nature. 2024 May;629(8012):624-629. doi: 10.1038/s41586-024-07316-0. Epub 2024 Apr 17.
The cost of drug discovery and development is driven primarily by failure, with only about 10% of clinical programmes eventually receiving approval. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval. 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.
药物发现和开发的成本主要由失败驱动，只有约 10%的临床项目最终获得批准。我们之前估计，人类遗传证据将临床开发到批准的成功率提高了一倍。在这项研究中，我们利用过去十年中遗传证据的增长来更好地了解区分临床成功和失败的特征。我们估计，具有遗传支持的药物机制成功的概率是没有遗传支持的药物机制的 2.6 倍。这种相对成功率因治疗领域和开发阶段而异，随着对因果基因的信心增加而提高，但基本不受遗传效应大小、次要等位基因频率或发现年份的影响。这些结果表明，我们远未达到利用遗传见解帮助发现更有效药物靶点的顶峰。
