ADDI's Editorial Take

What is it and what does it include? 

This is a phase I, open label, single dose, and parallel group study to assess short term pharmacodynamics and safety of GSK933776 (an anti-β amyloid monoclonal antibody for intravenous administration in the treatment of Alzheimer's disease). A total of 19 participants were included if they were 50 years or older and had probable mild Alzheimer's disease or MCI. The effect on the beta amyloid levels was assessed in early (MCI) and mild Alzheimer's disease (AD) patients after a single dose of GSK933776 by i.v. administration. Aβ and tau levels were investigated in cerebrospinal fluid (CSF), and the relationship between Aβ levels and Aβ modulation in plasma was explored.  

Has this dataset helped researchers understand Alzheimer’s and other dementias better? 

Of course!  

  • β-amyloid, GSK933776, Mild Alzheimer’s disease, Phase I study: 

In 2015, researchers found that GSK933776 demonstrated pharmacological activity and target engagement in CSF and plasma, and the continuous sampling method via a catheter successfully assessed the Aβ changes following single-dose administration of GSK933776. The results of this study demonstrate that the continuous sampling method using a catheter can be used successfully to assess Aβ changes after single-dose administration of an anti-Aβ antibody in patients with mild AD or MCI. April 2014 – DOI: 

  • Fc-Attenuated Anti-β Amyloid Antibody GSK933776, Randomized, Placebo-Controlled Study: 

In 2015, researchers observed typical pharmacokinetics for a mAb (monoclonal antibody) and evidence of target engagement in plasma and CSF. Inactivation of the Fc region is a key feature of GSK933776, which targets the Aβ N-terminus. This clinical evidence supports the hypothesis that an active Fc portion of mAbs directed against Aβ plays a role in the pathogenesis of ARIA-E (amyloid-related imaging abnormalities-edema). Hence GSK933776 may promise a better safety profile compared with existing anti-Aβ mAbs such as bapineuzumab and gantenerumab. Further studies are warranted to determine the tolerability profile and clinical efficacy of GSK933776 in patients with AD. March 2015 – DOI: