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Alzheimer's antibody charging towards Phase III trial

By Mike Nagle , 22-May-2007

An antibody designed to treat the debilitating symptoms of Alzheimer's disease is being prepared ahead of schedule for a final stage clinical trial.

Bapineuzumab (AAB-001) is a monoclonal antibody designed to enhance the body's own immune response against mild to moderate Alzheimer's disease. It is co-developed by Elan, based in Dublin, Ireland, and US pharma heavyweight Wyeth, who now plan to initiate a Phase III clinical trial as soon as possible.


Over 24 million people worldwide have dementia, and Alzheimer's disease is the most common cause according to Alzheimer's Disease International. A recent report in Alzheimer's & Dementia: The Journal of the Alzheimer's Association estimated the annual cost of dementia care was a staggering $315bn (€234bn). Although there are treatments that can slow the progression of the disease, there is currently no cure.


Bapineuzumab is currently in Phase II clinical trials, making it Elan's most advanced drug candidate against Alzheimer's. It received Fast Track status from the FDA in February 2006, which may speed up regulatory reviews.


A spokesperson for Elan told DrugResearcher.com that the decision to advance the clinical development of bapineuzumab is based on the continuing analysis of Phase I data of the drug and an interim analysis of the Phase II trial. This is also coupled with four and a half year follow-up data from the failed Phase II trial for Elan's earlier drug, AN-1792, and the seriousness of the disease.


However, the spokesperson also pointed out that the anticipated Phase III trial must first be approved by regulatory authorities - although they wouldn't say which ones. Elan hopes the study will begin in the second half of 2007, with the Phase II trial due to be completed in 2008. Until then, the company is keeping tight-lipped on the results from that mid-stage trial.


Elan's research focuses on the premise that the symptoms of Alzheimer's disease can be treated by reducing the amount of beta amyloid in the brain. This protein is thought to be involved in the formation of plaques, which in turn cause the nerve damage seen in those who suffer from the disease.


By dosing a patient with antibodies designed to bind to and clear beta amyloid peptide, it is hoped that bapineuzumab could eliminate the need for a patient to mount their own individual immune response. The drug is thought to clear both circulating and deposited beta amyloid from the brain. This 'passive immunisation' approach has been shown in animal studies to be equally effective at clearing beta amyloid from the brain as traditional 'active immunisation' methods, according to Elan.


The advantage of this approach is that safety problems associated with some active therapies will be reduced or eliminated as the treatment does not stimulate an immune response. Indeed, Elan's active immunotherapy, AN-1792, made it to Phase II before they pulled the plug in 2002. In the trial, 15 out of 360 patients treated with the product, experienced severe inflammation in the central nervous system that appeared to be directly linked to the vaccine.


The announcement has sent increased the share price of both companies. Elan's has increased over 12 per cent to $18.69 at the time of writing, whereas Wyeth shares are up 3.6 per cent to $58.41.


Amyloid beta is actually part of a larger protein called amyloid precursor protein (APP). This protein is sliced up by secretase enzymes to form the smaller amyloid beta peptide.


Samaritan Pharmaceuticals is also developing an amyloid busting compound. Caprospinol (SP 233) is thought to bind to the amyloid beta peptide Ab1-42 and block its aggregation into highly neurotoxic Amyloid Derived Diffusible Ligands (ADDLs). This ability might also explain the ability of caprospinol to wash amyloid plaques out of the brains of animals, as seen in studies completed by Samaritan.


Caprospinol binding to Ab1-42 also blocks the peptide from entering the mitochondria, one of its sites of toxin action, thus protecting mitochondrial function in an indirect manner. Having filed an Investigational New Drug (IND) application with the FDA last year, Samaritan are currently conducting further safety tests on the potential drug prior to it beginning Phase I development.