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Bapineuzumab and Alzheimer Disease

In September 2009, JANSSEN Alzheimer Immunotherapy, a subsidiary of Johnson & Johnson, acquired Elan’s Alzheimer's Immunotherapy Program (AIP), including Bapineuzumab. Bapineuzumab is an anti- Amyloid-beta (Aß) monoclonal antibody targeting the N-terminal region of the Aß protein. It was developed as a potential Alzheimers’ therapy as Aß protein aggregation contributes to the amyloid plaques on the brain which are characteristic of Alzheimer Disease (AD). It was considered to be a potentially useful antibody for use in passive immunotherapy in AD according to the amyloid cascade hypothesis.

However, Bapineuzumab has not fulfilled its promise as a potential AD therapy. Phase II clinical trials on patients with mild to moderate AD suggested that Bapineuzumab reduced CSF T-tau and P-tau proteins and reduced Aß burden in the brain. However, safety concerns were also raised, for example incidence of reversible vasogenic edema, particularly for higher doses of Bapineuzumab and in APOE epsilon4 carriers. Retrospective analysis also suggested increased risk of amyloid-related imaging abnormalities (ARIA) in APOE ɛ4 carriers and with high bapineuzumab dose, although with varying clinical associations. Furthermore, phase III trials did not convincingly show an impact of bapineuzumab on cognitive function. Johnson & Johnson ended Phase II testing of subcutaneous Bapineuzumab in July 2013 while phase III development of bapineuzumab IV in mild to moderate Alzheimer's was already discontinued in August 2012. An AD vaccine (ACC-001) is still being developed.

Current research suggests that moving from monoclonal antibodies such as Bapineuzumab towards intravenous polyclonal immunoglobulins may present a way forward for passive anti-amyloid immunotherapy in AD. Soluble Aß oligomers may also present a promising target. The international EU/US/CTAD Task Force have made various suggestions that could help ensure success in future clinical trials of AD drugs, including larger phase II studies, evidence of effects on downstream biomarkers before considering phase II tests and most importantly adopting measurement of cognition as the most reliable indicator of benefit.

Sources:
http://www.elan.com/development/clinical...e_diseases
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