Table 2. Anti-amyloid active and passive immunotherapy compounds in phase III secondary prevention trials for AD, with status updated as of late 2019 (only active trials).
| Agent | Mechanism of action | Mild to moderate AD | Early, preclinical or prodromal |
|---|---|---|---|
| CAD106 | Active immunotherapy (Aβ antigen) | One trial discontinued (no efficacy) | One preclinical AD trial ongoing – Generation S1 |
| Solanezumab | Passive immunotherapy (anti-Aβ monoclonal antibody) | Two trials discontinued (no efficacy) | One prodromal AD trial discontinued (strategic) Two preclinical AD trials ongoing – A4 and DIAN-TU |
| Crenezumab | Passive immunotherapy (anti-Aβ monoclonal antibody) | One trial discontinued (no efficacy) | Two preclinical AD trials ongoing – CREAD and CREAD2 |
| Gantenerumab | Passive immunotherapy (anti-Aβ monoclonal antibody) | One trial discontinued (no efficacy) One trial ongoing | One prodromal AD trial discontinued (no efficacy) Two early AD trials ongoing – GRADUATE 1 and GRADUATE 2 One preclinical AD trial ongoing – DIAN-TU |
| Aducanumab | Passive immunotherapy (anti-Aβ monoclonal antibody) | No trials at these AD stages | Two early AD trials discontinued (no efficacy in lower doses) – ENGAGE and EMERGE Reduced clinical decline with longer exposure to higher doses (results yet to be published) |
A4 = Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease Study; AD = Alzheimer’s disease; Aβ = amyloid-β; CREAD = A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants with Prodromal to Mild Alzheimer's Disease; DIAN-TU = Dominantly Inherited Alzheimer Network – Trials Unit; ENGAGE and EMERGE = A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Aducanumab in Patients with Early Alzheimer's Disease; Generation S1 = A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease; GRADUATE = A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients with Early Alzheimer's Disease.