Blind prediction of Phase II clinical outcome for new antipsychotic in schizophrenia

Drug with New Pharmacology for Schizophrenia

Background

• • • Development of compound with new pharmacology (part of clozapine) for schizophrenia as stand-alone
    • Candidate drug was effective in animal studies of schizophrenia
    • Candidate drug had no side-effect liability in animal studies of EPS
    • PET tracer available for drug exposure in humans

Proposed Quantitative Systems Pharmacology Solution

• • • Simulate competition with neurotransmitter on key receptors with PET imaging data
    • Simulation of full dose-response in PANSS Model and EPS liability as stand-alone

Outcome: Geerts (2012)

• • Calibrated QSP PANSS Total model suggested similar effect as comparator olanzapine
  • Calibrated QSP EPS model suggested much higher liability than with olanzapine
  • QSP model provided explanation of the observed translational disconnect