Bapineuzumab (nicknamed "bapi") is a

humanized monoclonal antibody Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal ant ...

that acts on the

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...

and may have potential therapeutic value for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and possibly

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

. 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 and

hyperphosphorylated Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problem ...

tau protein The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining ...

in CSF. 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. Bapineuzumab is an antibody to the

beta-amyloid Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which i ...

(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 using

active immunization Active immunization is the induction of immunity after exposure to an antigen. Antibodies are created by the recipient and may be stored permanently. Active immunization can occur naturally when microbes or other antigen are received by a person ...

had positive outcomes with removal of plaques, but 6% of subjects developed

aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, myco ...

and the trial was stopped.

Testing

Bapineuzumab was being co-developed by the pharmaceutical companies

Élan Elan Corporation plc was a major drugs firm based in Dublin, Ireland, which had major interests in the United States. It was listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN. ...

and

Wyeth Wyeth, LLC was an American pharmaceutical company. The company was founded in Philadelphia, Pennsylvania, in 1860 as ''John Wyeth and Brother''. It was later known, in the early 1930s, as American Home Products, before being renamed to Wyeth in ...

and entered

Phase III trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s in December 2007. In 2008 a

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...

affiliate acquired a substantial portion of Élan's assets related to the Alzheimer's

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

program, which Elan had shared with Wyeth. The program is continuing with

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

, which acquired Wyeth in 2009. Bapineuzumab was the first antibody to be found to cause

amyloid-related imaging abnormalities Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in magnetic resonance imaging of the brain in patients with Alzheimer's disease. ARIA is associated with amyloid-modifying therapies, particularly human monoclonal antibodi ...

, including an accumulation of fluid in brain tissue ( ARIA-E) 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. The efficacy of drugs targeted to

brain plaques Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...

in Alzheimer's patients has been called into question, although such drugs may still be effective for

prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

if given to individuals who have not yet developed clinical symptoms. On August 6, 2012,

Pfizer Inc Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

. and

said they are ending development of an

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

formulation of bapineuzumab. Testing showed the drug did not work better than

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

in two late-stage trials in patients who had mild to moderate Alzheimer's disease. Élan announced that Johnson & Johnson, on July 16, 2013, had discontinued Phase 2 testing of the subcutaneous formulation of bapineuzumab.

Insider trading

Mathew Martoma Mathew Martoma (born May 18, 1974, as Ajai Mathew Mariamdani Thomas) is an American former hedge fund trader. As a portfolio manager at S.A.C. Capital Advisors, he was accused of generating possibly the largest single insider trading transaction ...

, formerly of

S.A.C. Capital Advisors SAC Capital Advisors was a group of hedge funds founded by Steven A. Cohen in 1992. The firm employed approximately 800 people

, was convicted in February 2014 of

insider trading Insider trading is the trading of a public company's stock or other securities (such as bonds or stock options) based on material, nonpublic information about the company. In various countries, some kinds of trading based on insider information ...

on news passed by neurologist Sid Gilman of the cancellation of bapineuzumab's testing.

References

{{Monoclonals for bone, musculoskeletal, circulatory, and neurologic systems Wyeth brands Pfizer brands Treatment of Alzheimer's disease