Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Flatiron Health, Washington, District of Columbia, USA.
Clin Infect Dis. 2021 Dec 6;73(11):e4444-e4450. doi: 10.1093/cid/ciaa859.
We present a longitudinal analysis of investigational new drug applications (INDs) for new, systemic antibacterial drugs under active development between 1980 and 2019, evaluating the characteristics of these investigational drugs and the outcomes of these drug development programs. The number of INDs in active development declined by two-thirds, from 39 active INDs at its peak in 1987 to a low 13 in 2001, with decreased development of new cephalosporin, quinolone, and macrolide drugs and reduced participation from large pharmaceutical firms. Antibacterial drug development activity rebounded substantially from 2002 to 2009, primarily led by involvement of small pharmaceutical companies. As of 31 December 2019, the number of active INDs has declined to an 11-year low, and the number of antibacterial INDs initiated with the US Food and Drug Administration during 2010-2019 was lower than any of the previous 3 decades. Antibacterial drug development programs initiated in the 1980s and 1990s had high success rates, with >40% of INDs obtaining marketing approval, in a median time of about 6 years from IND receipt to approval. For drug development programs initiated between 2000 and 2009, we found that IND-to-approval rates reduced to 23%, with median development times for approved antibacterial drugs increasing to 8.2 years. The majority of INDs in development as of 31 December 2019 come from already established drug classes, most in early stages of development, and few are sponsored by large pharmaceutical companies.
我们对 1980 年至 2019 年间处于积极研发阶段的新型全身抗菌药物的研究性新药申请（IND）进行了纵向分析，评估了这些研究性药物的特征和这些药物开发项目的结果。处于积极研发阶段的 IND 数量减少了三分之二，从 1987 年的 39 个高峰降至 2001 年的 13 个低点，新型头孢菌素、喹诺酮和大环内酯类药物的研发减少，大型制药公司的参与度降低。从 2002 年到 2009 年，抗菌药物的研发活动大幅反弹，主要由小型制药公司参与。截至 2019 年 12 月 31 日，处于活跃状态的 IND 数量已降至 11 年来的最低点，2010 年至 2019 年期间，美国食品和药物管理局启动的抗菌 IND 数量低于前 30 年的任何一年。在 20 世纪 80 年代和 90 年代启动的抗菌药物开发项目成功率较高，超过 40%的 IND 获得了营销批准，从 IND 收到到批准的中位数时间约为 6 年。对于 2000 年至 2009 年启动的药物开发项目，我们发现 IND 到批准的比率降至 23%，获得批准的抗菌药物的中位数开发时间增加到 8.2 年。截至 2019 年 12 月 31 日，处于开发中的大多数 IND 来自已有的药物类别，大多数处于早期开发阶段，很少有大型制药公司赞助。
