Table 1.

Overview of amyloid β (Aβ)-directed antibodies being tested in clinical trials. Further information can be found on https://clinicaltrials.gov/. PI, PII, and PIII refer to phases one, two, and three of clinical trials, respectively. AD: Alzheimer’s disease; ARIA: amyloid-related imaging abnormality; FAD: Familial Alzheimer’s Disease; IV: intravenous; SC: subcutaneous.

Antibody/IgG Subtype	Company	Specificity	Dosage	Development Stage
Bapineuzumab/IgG1 AAB-001 (humanized mouse 3D6)	Janssen/Pfizer	Aβ 1–5 (helical, N-terminal D sensitive)	PI: 12-month 0.5, 1.5, or 5 mg/kg PII: 18-month 0.15, 0.5, 1, or 2 mg/kg PIII: 18-month 0.5 mg/kg 1.0 mg/kg	Terminated in August 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns [24,34]
AAB-003 (PF-05236812) humanized and IgG1 Fc-engineered (Effector function reduced variant of bapineuzumab)	Janssen/Pfizer	Aβ 1–5 (helical, N-terminal D sensitive)	PI: 0.5, 1, 2, 4, 8 mg/kg	Completed 2016, lower toxicity (ARIAs) compared to Bapineuzumab was expected, continuation as open-label extension study to February 2017 [35], discontinued in January 2018 by Pfizer.
Ponezumab (PF-04360365, RN1219) IgG2 (humanized mouse monoclonal antibody)	Pfizer (developed by Rinat Nsc.)	binds the free carboxy-terminal amino acids 33–40 of Aβ 1–40	PII 10 mg/kg 2009–2011 PII 8.5 mg/kg 2008–2011	Nov 2011, Pfizer Inc. discontinued development of ponezumab [36,37]
Solanezumab (LY2062430) IgG1 (humanized mouse 266])	Eli Lilly	Aβ 16–26 accessible only on monomeric Aβ	PIII 2009–2012EXPEDITION PIII 2010–2014 EXPEDITION EXT PIII 2013–2016 EXPEDIRION 3 PIII 2016–2017 EXPEDITION PRO (solanezumab 400 milligrams (mg) every 4 weeks for 76 weeks PIII A4 (2014–2022) 400–1600 mg IV every 4 weeks for 240 weeks	Failed in 2012 in primary endpoint and terminated in May 2017. Insufficient scientific evidence that solanezumab would likely demonstrate a meaningful benefit to patients with prodromal AD as defined by the study protocol [25,38]. Active in FAD PIII DIAN-TU (2012–2023) [39] Active in PIII A4 study in older individuals at risk for AD (2014–2022)
LY3002813 IgG1 (humanized mouse mE8-IgG2a)	Eli Lilly	pE3-Aβ	0.1 mg/kg to 10 mg/kg, infused monthly up to four times, and a single subcutaneous injection against placebo for safety	PI 2017–2020 No cases of ARIA were seen in this small trial, but there were two asymptomatic cases of ARIA-H (hemorrhage). The antibody was reported to be strongly immunogenic [40,41]. PII 2017–2020 in combination with BACE inhibitor LY3202626 in early symptomatic AD (ClinicalTrials.gov Identifier: NCT03367403)
Gantenerumab (RG1450, RO4909832) IgG1 (full human)	Hoffmann-La Roche	Aβ 2–5 (−9) + 23–25 bind with subnanomolar affinity to a conformational epitope on Aβ fibrils. It binds both N-terminal and central amino acids of Aβ	PIII 225 mg SC 2010–2019 FAD PIII DIAN-TU (2012–2023) two new PI trials started 2016, investigating subcutaneous administration of higher doses of gantenerumab.	PIII active On March 6, 2017, MorphoSys, which partners in the development of gantenerumab, announced Roche will start two new Phase 3 trials of the immunotherapy for prodromal AD in 2017 [42].
Crenezumab (RG7412, MABT5102A) IgG4 (humanized mouse MABT5102)	Genentech 8 discov. by AC immune)	Aβ 13–24 (conformational epitopes?) Binds fibrillar, oligomeric, and monomeric Abeta.	PIII CRED 2016–2020 [21] up to 60 mg/kg PII (2013–2022) SC (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks	PIII CREAD 2 2017–2022 [33,43] Prodromal to mild AD; mild to moderate AD (2 different trials) PII FAD PSEN1 E280A autosomal-dominant mutation carriers
BAN2401 IgG1 (humanized mAb158)	Eisai (discov. by BioArctic) 2014 coll. with Biogen	recognizes Aβ protofibrils	two PI: 2.5, 5 and 10 mg/kg PII: 2.5, 5 and 10 mg/kg	PII 2012–2018 patients with early AD [44,45,46]
Aducanumab IgG1 (BIIB037/BART full human)	Biogen (discov. by Neuri-Mmune)	recognizes Aβ oligomer and fibrils	PIb PRIME PIII ENGAGE 2015–2022 dosage unknown PIII EMERGE 2015–2022 dosage unknown	PIII in prodromal AD patients [26,47,48]
SAR228810 (humanized Ab 13C3); IgG4 (like) framework	Sanofi	recognizes Aβ protofibrils	PI 2012–2015 study to assess the safety and the concentration-time profile with IV and SC injection	PI [49]
MEDI1814 IgG1 3x mut ADCC-, CDC-	AstraZeneca	selective for Aβ42 C-terminus	PI 2014–2016 (2017) for IV and SC injection; 25 to 1800 mg total	PI [50]
GSK933776 (humanized, IgG1 reduced in ADCC and CDC)	GlaxoSmithKline	against the N-terminus of the Aβ	PI: 1, 3, or 6 mg/kg	No further development in AD. In 2015, this antibody was in PII for retinal amyloidosis in connection with dry age-related macular degeneration (dry AMD) [51,52]
RN6G (Pf-04382923) IgG2 (humanized mouse monoclonal antibody)	Pfizer (dev. By Rinat Neuroscience)	C-terminus of Aβ, no differentiation between 40/42	PII 2012–2013 IV injection 2.5 mg/kg up to a maximum of 15 mg/kg	PII Developed in dry AMD [53]