From: The “rights” of precision drug development for Alzheimer’s disease
Right element | Target identification | Drug candidate optimization | Non-clinical assessment | Phase 1 | Phase 2 | Phase 3 |
---|---|---|---|---|---|---|
Target | Druggable target identified in AD biology | PD effect supported | PD effect may be assessed with biomarkers | PD effect supported by biomarkers | PD effect supported by biomarkers and clinical outcomes | |
Drug | Chemical properties | ADME; toxicity; efficacy in animals | PK, ADME in healthy volunteers; MTD established; BBB penetration established | PK, PD in AD | PD in AD | |
Biomarker | Development of biomarkers useful in trials | Toxicity biomarkers | Patient selection; target engagement biomarkers | Patient selection; DM; toxicity; predictive biomarkers | ||
Patient | Healthy volunteers; AD for immuuno-therapy trials | Prodromal AD, AD dementia | High-risk normal subjects; prodromal AD; AD dementia | |||
Trial | Single ascending dose; multiple ascending dose | Drug-placebo difference at endpoint; adaptive designs | Drug-placebo difference at endpoint; adaptive designs; delay to milestone |