Challenges of Psychiatry Drug Development and the Role of Human Pharmacology Models in Early Development—A Drug Developer's Perspective

Psychiatric diseases have the lowest probability of success in clinical drug development. This presents not only an issue to address the unmet medical needs of patients, but also a hurdle for pharmaceutical and biotech industry to continue R&D in this disease area. Fundamental pharmacokinetic and pharmacodynamic principles provide an understanding of the drug exposure, target binding and pharmacological activity at the target site of action for a new drug candidate. Collectively, these principles determine the likelihood of testing the mechanism of action and enhancing the likelihood of candidate survival in Phase 2 clinical development, therefore, they are termed as the “three pillars of survival.” Human Phase 1 pharmacokinetic and pharmacodynamic studies provide evidence of the three pillars. Electroencephalogram (EEG) assessments and cognitive function tests in schizophrenia patients can provide proof of pharmacology and ensure that a pharmacological active regimen will be tested in Phase 2 proof of concept (POC) studies for the treatment of cognitive impairment associated with schizophrenia (CIAS).