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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
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)