Table 1 Principal failed clinical studies on anti-Aβ therapies in AD and related disorders

From: A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease

Drug Company Mechanism of action Patient population Trial phase Main reasons for failure Remarks
2002
AN-1792 (ref.35) Elan Aβ antigen Mild to moderate AD II Toxicity and lack of efficacy
2007
Tramiprosate204 Neurochem Aβ aggregation inhibitor Mild to moderate AD III Lack of efficacy
2009
Tarenflurbil205 Myriad Genetics/Lundbeck γ-Secretase modulator Mild AD III Lack of efficacy Worsens global status
Scyllo-inositol206 Transition Therapeutics/Elan Aβ aggregation inhibitor Mild to moderate AD II Toxicity and lack of efficacy • Increases mortality
• Inactivates Aβ oligomers
2010
Begacestat207 Wyeth γ-Secretase inhibitor Mild to moderate AD II Toxicity and lack of efficacy
2011
Ponezumab208 Pfizer Anti-Aβ monoclonal antibody Mild to moderate AD II Lack of efficacy
Semagacestat209 Eli Lilly γ-Secretase inhibitor Mild to moderate AD III Toxicity and lack of efficacy Worsens cognition
2012
Bapineuzumab210 Elan/Wyeth Anti-Aβ monoclonal antibody Mild to moderate AD III Lack of efficacy
Avagacestat211 Bristol-Myers Squibb γ-Secretase inhibitor Mild to moderate AD II Toxicity and lack of efficacy Worsens cognition
Avagacestat212 Bristol-Myers Squibb γ-Secretase inhibitor Prodromal AD II Toxicity and lack of efficacy Worsens cognition
2013
Solanezumab49 Eli Lilly Anti-Aβ monoclonal antibody Mild to moderate AD III Lack of efficacy
Vanutide36 Janssen Aβ antigen Mild to moderate AD II Lack of efficacy
Immunoglobulin213 Baxter Anti-Aβ polyclonal antibody Mild to moderate AD III Lack of efficacy
LY2886721 (ref.214) Eli Lilly β-Secretase inhibitor Mild to moderate AD II Toxicity
AZD3839 (ref.215) AstraZeneca β-Secretase inhibitor Healthy volunteers I Toxicity
2014
Affitope AD02 (ref.216) Affiris/GlaxoSmithKline Aβ antigen Early AD II Lack of efficacy Worsens cognition
CAD106 (ref.40) Novartis Aβ antigen Mild AD II Lack of efficacy Worsens cognition
PBT2 (ref.217) Prana Biotechnology Aβ aggregation inhibitor Prodromal AD II Lack of efficacy
Crenezumab65 Genentech/Roche Anti-Aβ monoclonal antibody Mild to moderate AD II Lack of efficacy Binds oligomeric Aβ
Gantenerumab57 Chugai/Roche Anti-Aβ monoclonal antibody Prodromal AD II Lack of efficacy Binds oligomeric Aβ
Gantenerumab59 Chugai/Roche Anti-Aβ monoclonal antibody Mild AD II Lack of efficacy Binds oligomeric Aβ
2016
Solanezumab50 Eli Lilly Anti-Aβ monoclonal antibody Mild AD III Lack of efficacy
Solanezumab218 Eli Lilly Anti-Aβ monoclonal antibody Prodromal AD III Strategic
Verubecestat80 Merck BACE inhibitor Mild to moderate AD III Lack of efficacy Increases mortalityWorsens cognition
2018
Verubecestat82 Merck BACE inhibitor Prodromal AD III Lack of efficacy Worsens cognition
Atabecestat96 Janssen BACE inhibitor Asymptomatic at risk of AD III Toxicity Worsens cognition
Lanabecestat88 • Astra
• Eli Lilly
BACE inhibitor Early AD III Lack of efficacy Worsens cognition
Lanabecestat88 • Astra
• Eli Lilly
BACE inhibitor Mild AD III Lack of efficacy Worsens cognition
  1. Studies are grouped by year of publication of the main results. Aβ, amyloid-β; AD, Alzheimer disease; BACE, β-secretase.