Table 2 Development of symptomatic cognitive enhancing drugs compared to development of disease-modifying agents
From: New approaches to symptomatic treatments for Alzheimer’s disease
Development | Symptomatic Cognitive Enhancing Agent | Disease-Modifying Agent |
|---|---|---|
Approved agents | Yes | No |
Defined regulatory pathway | Yes | No |
Validated target | Yes | No |
Conventional target | Yes; receptors and ion channels | Some conventional targets such as enzymes and some unconventional targets such as protein-protein interactions |
Clinical outcomes validated in successful trials | Yes | No |
Trial sample size | 200–400 per arm | 600–1200 per arm |
Trial duration | 3–6 months | 12–24 months |
Administration | Oral; patch | Oral; intravenous; subcutaneous; intramuscular |
Patient convenience | More convenient; usually orally administered | Less convenient if intravenous, subcutaneous, or intramuscular administration required |
Diagnosis | Usually phenotype-based | Phenotype-based usually with biomarker confirmation |
Target engagement biomarker | May not be included | Yes |
Disease-modification biomarker | No | Yes |
Preclinical application | No; symptoms required | Yes; trials can be biomarker based |
Prodromal application | Yes; none approved | Yes; none approved |
Alzheimer dementia application | Yes; approved | Yes, none approved |
Increasing drug-placebo difference over time | No; cumulative benefit not anticipated | Yes; cumulative benefit anticipated |
Delayed start or randomized withdrawal trial design show enduring effect of treatment | No | Yes |
Cost of development program | Lower | Higher |
Cost of treatment to patients | Lower | Higher |
Patient message | Improved ability above baseline function | No improvement; less decline over time; delayed onset of dementia (in predementia populations) |