A much-anticipated phase III trial of bapineuzumab, an antibody therapy for Alzheimer's disease in development at Pfizer, Johnson & Johnson and Elan, has ended in disappointment.
Bapineuzumab was unable to achieve significant increases in cognitive and functional performance, the co-primary endpoint in study 302, which enrolled patients with mild-to-moderate Alzheimer's disease who carry a gene called apolipoprotein E epsilon 4 (ApoE4).
Pfizer and J&J said that given the lack of efficacy patients who enrolled in a follow-on extension study would not be treated with the antibody, which is designed to break down the amyloid plaques that are characteristic of Alzheimer's disease.
The results are another blow to the so-called 'amyloid hypothesis' of Alzheimer's, which suggests that these plaques are the trigger for the neurodegeneration seen in patients.
The results have not come as a surprise, however, as several other drugs designed to target amyloid have already failed in trials - including Neurochem's Alzhemed (tramiprosate), Lundbeck/Myriad Genetics' Flurizan (r-flurbiprofen), Eli Lilly's semagacestat and Elan's ELND007.
That has led to speculation that amyloid triggers other events which underlie the neurodegeneration in Alzheimer's, so targeting already-present plaques is redundant.
Pfizer and J&J have been quick to point out that Study 302 is one of four phase III trials being conducted with bapineuzumab, with results in other forms of Alzheimer's disease such as non-ApoE4 carriers due later this year.
ApoE4 is a risk factor for Alzheimer's, and carriers tend to exhibit increased levels of amyloid plaques in their brains.
“While we are disappointed in the topline results of Study 302, a more complete understanding of bapineuzumab and its potential utility in mild-to-moderate Alzheimer's disease will be gained following the availability of additional data," said Steven Romano, the head of Pfizer's primary care medicines development group.
Meanwhile, the amyloid hypothesis will undergo a further test later this year when late-stage results with another amyloid-targetting therapy, Eli Lilly's solanezumab, are revealed.