Affiliations: [a] Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands | [b] Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| [c] Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| [d] Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| [e] CHDI Management/CHDI Foundation, Princeton, NJ, USA
| [f] Department of Clinical Pharmacology and Neurosciences, Centre d’Investigation Clinique CIC1436, NS-Park/FCRIN Network, UMR ToNIC 1214, University Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France
| [g] CNS – Campus Neurológico Sénior, Torres Vedras, Portugal
Correspondence to: Joaquim J. Ferreira, MD, PhD, Avenida Prof. Egas Moniz, 1649-028, Lisboa, Portugal. E-mail: [email protected].
Note:  These authors contributed equally to this study.
Abstract: Background: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. Objective:To indirectly assess drug development programs in Parkinson’s disease, exploring some factors associated with compound attrition at different trial phases. Methods: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. Results: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. Conclusion: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.
Keywords: Clinical development, drug development, clinical trials, parkinson’s