Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
J Parkinsons Dis. 2021;11(2):421-429. doi: 10.3233/JPD-202184.
A global overview of drug development programs in Parkinson's disease over the last few decades is lacking, while such programs are challenging given the multifaceted and heterogeneous nature of the disease.
To indirectly assess drug development programs in Parkinson's disease, exploring some factors associated with compound attrition at different trial phases.
We assessed all Parkinson's disease trials in the WHO trials portal, from inception (1999) to September 2019. Independent authors selected trials and extracted data. The success rate was the number of compounds that progressed to the next drug development phase divided by the number of compounds in that phase.
Overall, 357 trials (studying 152 compounds) fulfilled our inclusion criteria, with 62 (17.3%) phase 1 trials, 135 (37.8%) phase 2 trials, 85 (23.8%) phase 3 trials, and 53 (14.8%) phase 4 trials. The success rate was 42.4% from phase 2 to 3. Original compounds received regulatory approval by the FDA in 21.4% of cases, compared with 6.7% of repurposed compounds, representing an overall success rate of 14.9%. We found 172 trials (48.2%) conducted for repurposing previously licensed compounds. These figures were approximately the same regarding approval by the EMA. Most compounds were approved to treat parkinsonism and motor fluctuations.
We found a moderate-to-high success rate in all phases of drug development. This was largely based on the success of original compounds, despite almost half of the identified trials attempting compound repurposing.
过去几十年，全球范围内缺乏帕金森病药物研发项目的综述，鉴于该疾病具有多方面和异质性的特点，此类项目极具挑战性。
旨在间接评估帕金森病的药物研发项目，探索不同试验阶段与化合物淘汰相关的一些因素。
我们评估了世界卫生组织试验门户中自 1999 年成立至 2019 年 9 月期间所有的帕金森病试验。独立作者选择试验并提取数据。成功率是指进入下一药物研发阶段的化合物数量与该阶段化合物数量的比值。
总体而言，有 357 项试验（研究了 152 种化合物）符合我们的纳入标准，其中 62 项（17.3%）为 1 期试验，135 项（37.8%）为 2 期试验，85 项（23.8%）为 3 期试验，53 项（14.8%）为 4 期试验。从 2 期到 3 期的成功率为 42.4%。原始化合物获得 FDA 监管批准的比例为 21.4%，而重新定位化合物的批准比例为 6.7%，总成功率为 14.9%。我们发现有 172 项（48.2%）试验是为重新定位以前批准的化合物而进行的。在 EMA 批准方面，这些数据大致相同。大多数化合物被批准用于治疗帕金森病和运动波动。
我们发现药物研发的所有阶段都有中高成功率。这主要基于原始化合物的成功，尽管近一半的已识别试验都试图重新定位化合物。
