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Posted by on Jul 21, 2008 in Neurology, Pharma

Elan’s AN1792: No Clinical Benefit With Clearance of Amyloid Plaques in AD

Elan’s AN1792: No Clinical Benefit With Clearance of Amyloid Plaques in AD


Immunization with synthetic amyloid beta (AN1792; Elan) clears amyloid plaques in brain but is not associated with improved cognition or survival in the long term, according to a small UK study of patients with Alzheimer’s disease (AD). Results of the placebo-controlled trial, funded by the Alzheimer’s Research Trust, were published in this month’s issue of The Lancet.

A total of 80 patients with probable mild-to-moderate AD received either randomly assigned AN1792 (50 or 225 ug) with adjuvant (n = 64) or adjuvant alone (n = 16).* Postmortem examination of 8 actively treated AD patients revealed a significantly lower Aβ load than that in nonimmunized controls.However, the investigators noted considerable variation of the Aβ load and the extent of plaque removal among immunized cases.

There was no relationship between the dose of AN1792 and Aβ load or postmortem plaque removal, but the mean antibody response during treatment showed a nonsignificant correlation with Aβ load. Seven of the 8 patients, including those who demonstrated “virtually complete plaque removal,” exhibited severe end-stage dementia, and there were no survival or cognitive differences between the immunized and placebo-treated groups.

A phase 2a study of AN1792 was halted when 6% of patients developed meningoencephalitis. The study did not show relative cognitive improvement at 1 year with immunization, despite the presence of high levels of Aβ antibodies. In June, Elan and Wyeth announced favorable results with the anti-Aβ monoclonal antibody bapineuzumab in mild-moderate AD, despite the fact that the primary endpoint in the phase 2 trial was not met.

* In a protocol extension, patients received either AN1792 (n = 51) or adjuvant alone (n = 13) in a modified formulation to increase Aβ solubility.

Because no patients in the placebo-treated group underwent postmortem examination, histologic findings in an age-matched, nonimmunized control group of patients with AD were used for comparison.

Image of wild-type amyloid precursor protein (left) and amyloid fibril (right) by David S. Goodsell from Wikimedia Commons.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.

1 Comment

  1. Aloha Barbara~
    I saw this article coming from my “Medical News Today” e-mail. Tried to find out about this AN1792 and saw this website. I sent in a reply to the MNT article which is this: “All efforts to stabilize or reverse ALZ will not work unless the underlying condition of Oxidative Stress is ameliorated! It’s not only going to take GSH, but a combination of components to have the greatest result!
    Aloha, Gil