Background

AAB-003 is a humanized version of the anti-Aβ mouse antibody 3D6 and a derivative of bapineuzumab (AAB-001). AAB-003 was modified to differ from bapineuzumab in its Fc fraction in hopes of reducing the antibody’s effector function on microglial activation. The rationale was that this would avoid amyloid-related imaging abnormalities (ARIA), a complication of bapineuzumab treatment (Crespi et al., 2014; Moreth et al., 2013).

Findings

Starting in September 2010, Pfizer and Janssen AIP conducted a double-blind Phase 1 trial with an open-label extension at centers in the United States and South Korea. The adaptive trial compared multiple infusions each of five different doses of AAB-3 to placebo in 88 patients with mild to moderate Alzheimer's disease who had an MRI scan consistent with their clinical diagnosis. The 41-week trial measured safety parameters including MRI evidence of ARIA. Secondary measures included immunogenicity of the antibody, biomarker CSF measurements of Aβ and tau, as well as cognitive and clinical scales such as the ADAS-cog, DAD, and others. In July 2011, the open-label extension study started enrolling people who had completed the blinded trial for a further year of treatment and observation on the same outcome measures. This trial was completed in August 2014. According to published results, AAB-003 showed dose-dependent increases in plasma Aβ but no change CSF Aβ, and ARIA and microhemorrhages (Delnomdedieu et al 2016). 

For all clinical trials on AAB-003, see clinicaltrials.gov.