| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (frommouse) |
| Target | beta-amyloid (Aβ) |
| Clinical data | |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| ECHA InfoCard | 100.133.214 |
| Chemical and physical data | |
| Formula | C6466H10018N1734O2026S44 |
| Molar mass | 145874.02 g·mol−1 |
 N Y (what is this?) (verify) | |
Bapineuzumab (nicknamed "bapi")[1] is ahumanized monoclonal antibody that acts on thenervous system and may have potential therapeutic value for the treatment ofAlzheimer's disease and possiblyglaucoma.[2] However, in 2012 it failed to produce significant cognitive improvements in patients in two major trials, despite lowering key biomarkers of AD, amyloid brain plaque andhyperphosphorylatedtau protein inCSF.[3][4]
Bapineuzumab has been shown to recognise the extreme N-terminal 5 residues of Aβ peptide in a helical conformation (4HIX.pdb) stabilized by internal hydrogen bonds involving the first three amino acids.[5]
Bapineuzumab is an antibody to thebeta-amyloid (Aβ) plaques that are believed to underlie Alzheimer's disease neuropathology. In previous clinical trials for vaccination against human beta amyloid, called AN-1792, patients with Alzheimer's disease usingactive immunization had positive outcomes with removal of plaques, but 6% of subjects developedaseptic meningitis and the trial was stopped.[6]
Bapineuzumab was being co-developed by the pharmaceutical companiesÉlan andWyeth and enteredPhase III trials in December 2007.[7] In 2008 aJohnson & Johnson affiliate acquired a substantial portion of Élan's assets related to the Alzheimer'simmunotherapy program, which Elan had shared with Wyeth. The program is continuing withPfizer, which acquired Wyeth in 2009.
Bapineuzumab was the first antibody to be found to causeamyloid-related imaging abnormalities, including an accumulation of fluid in brain tissue (ARIA-E)[8] in patients receiving the highest dose. No health risks were found in subjects receiving either 0.5 or 1 mg of bapineuzumab. Patients who have been receiving or have been scheduled to receive the highest dose will be either removed from the trials or switched to lower doses.[9]
The efficacy of drugs targeted tobrain plaques in Alzheimer's patients has been called into question, although such drugs may still be effective forprophylaxis if given to individuals who have not yet developed clinical symptoms.[10][11]
On August 6, 2012,Pfizer Inc. andJohnson & Johnson said they are ending development of anintravenous formulation of bapineuzumab. Testing showed the drug did not work better thanplacebo in two late-stage trials in patients who had mild to moderate Alzheimer's disease.[11]
Élan announced that Johnson & Johnson, on July 16, 2013, had discontinued Phase 2 testing of thesubcutaneous formulation of bapineuzumab.[12]
Mathew Martoma, formerly ofS.A.C. Capital Advisors, was convicted in February 2014 ofinsider trading[13] on news passed by neurologistSid Gilman of the cancellation of bapineuzumab's testing.[14]
The vigour of international research on immunotherapy for AD provides significant hope for a strong therapeutic lead for the escalating number of individuals who will develop this otherwise incurable condition.
Elan and Wyeth plan to continue all four studies in the previously disclosed bapineuzumab Phase 3 clinical program
