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Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease


Salloway, Stephen, Sperling, Reisa, Fox, Nick C., Blennow, Kaj, Klunk, William, Raskind, Murray, Sabbagh, Marwan, Honig, Lawrence S., Porsteinsson, Anton P., Ferris, Steven, Reichert, Marcel, Ketter, Nzeera, Nejadnik, Bijan, Guenzler, Volkmar, Miloslavsky, Maja, Wang, Daniel, Lu, Yuan, Lull, Julia, Tudor, Iulia Cristina, Liu, Enchi, Grundman, Michael, Yuen, Eric, Black, Ronald, Brashear, H. Robert


The New England Journal Of Medicine, Volume: 370, No.: 4, Pages.: 322-333

Year of Publication



Background: Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer’s disease.; Methods: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer’s disease–one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks. The primary outcome measures were scores on the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100 and higher scores indicating less impairment). A total of 1090 carriers and 1114 noncarriers were included in the efficacy analysis. Secondary outcome measures included findings on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations.; Results: There were no significant between-group differences in the primary outcomes. At week 78, the between-group differences in the change from baseline in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were -0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8 (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and 0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was amyloid-related imaging abnormalities with edema among patients receiving bapineuzumab, which increased with bapineuzumab dose and APOE ε4 allele number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between-group differences were observed with respect to PIB-PET and cerebrospinal fluid phospho-tau concentrations in APOE ε4 allele carriers but not in noncarriers.; Conclusions: Bapineuzumab did not improve clinical outcomes in patients with Alzheimer’s disease, despite treatment differences in biomarkers observed in APOE ε4 carriers. (Funded by Janssen Alzheimer Immunotherapy and Pfizer; Bapineuzumab 301 and 302 numbers, NCT00575055 and NCT00574132, and EudraCT number, 2009-012748-17.).;

Bibtex Citation

@article{Salloway_2014, doi = {10.1056/nejmoa1304839}, url = {}, year = 2014, month = {jan}, publisher = {New England Journal of Medicine ({NEJM}/{MMS})}, volume = {370}, number = {4}, pages = {322--333}, author = {Stephen Salloway and Reisa Sperling and Nick C. Fox and Kaj Blennow and William Klunk and Murray Raskind and Marwan Sabbagh and Lawrence S. Honig and Anton P. Porsteinsson and Steven Ferris and Marcel Reichert and Nzeera Ketter and Bijan Nejadnik and Volkmar Guenzler and Maja Miloslavsky and Daniel Wang and Yuan Lu and Julia Lull and Iulia Cristina Tudor and Enchi Liu and Michael Grundman and Eric Yuen and Ronald Black and H. Robert Brashear}, title = {Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer{textquotesingle}s Disease}, journal = {New England Journal of Medicine} }


adverse effects, aged, aged, 80 and over, alzheimer disease, analysis, antagonists inhibitors, antiamyloidbeta, antibodies monoclonal humanized, antibody, apolipoproteins e, bapineuzumab, biological markers, brain, cerebrospinal fluid, chemically induced, cognition, double-blind method, drug effects, drug therapy, edema, female, genetics, humanized, humans, intention to treat analysis, male, middle aged, monoclonal, neuropsychological tests, pathology, phosphorylation, severity of illness index, tau proteins, therapeutic use, treatment failure

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions