Bapineuzumab Disappoints in 1st of 4 Late-Phase Alzheimer Trials
In a development that isn’t terribly surprising, Pfizer released disappointing data yesterday evening from its (and Janssen’s) phase 3 study of the anti-amyloid MAb bapineuzumab in patients with mild-moderate Alzheimer disease. This study, in which enrollees carry 1 or 2 APOE ε4 alleles (a risk factor for AD and a higher burden of brain amyloid), did not meet its co-primary clinical endpoints: a change in cognitive and global functions. Details of this trial, and those of a companion trial of bapineuzumab in non-APOE ε4 carriers, will be presented in early September at the EFNS meeting in Stockholm.
The enrollees (APOE ε4 positive) who received bapineuzumab in the negative phase 3 study will not receive the treatment in an extension of the trial, but they will undergo follow-up, Pfizer says. What will be interesting to learn more about from this study (labeled 302) is 1) whether there was definite PET evidence of amyloid clearing in the bapineuzumab-treated patients; and 2) whether some portion of these patients developed asymptomatic or symptomatic ARIA (eg, vasogenic edema or microhemorrhages)—findings which have been linked to the immune-mediated clearance of amyloid from the brain.
Pfizer also reminds us that 2 other phase 3 studies of bapineuzumab are underway (see the table here for a list of registered bapineuzumab studies), the results of which are expected in 2013 and 2014. One of these studies is in APOE ε4 carriers. Depending on the imminent outcome of the phase 3 study of the MAb in non-APOE ε4 carriers, perhaps Pfizer and Janssen will make a decision about the developmental fate of bapineuzumab. Maybe they will forgo further investigation of the MAb in frank AD and focus on earlier stages of dementia—namely, MCI. A big part of that decision will rest on the relative safety and tolerability of bapineuzumab in the most-advanced phase 3 trials of AD.
ARIA = amyloid-related imaging abnormalities; MAb = monoclonal antibody; MCI = mild cognitive impairment; PET = positron emission tomography.