Alzheimer's Vaccine Permanently Shelved
By Rick Weiss
Washington Post Staff Writer
Saturday, March 2, 2002; Page A03
A once-promising experimental Alzheimer's vaccine that was reported last week to have triggered a dozen cases of brain inflammation in human volunteers has caused similar complications in an additional three people and has been permanently withdrawn from human testing.
The vaccine, under development by the Irish pharmaceutical company Elan in conjunction with Wyeth-Ayerst Laboratories, a division of American Home Products Corp. of Madison, N.J., had raised unusually high hopes after it had halted and even reversed an Alzheimer's-like condition in mice. It had passed initial safety studies in Britain and was being tested in about 300 people in four European countries and 11 U.S. medical centers.
Elan suspended inoculations in mid-January after four volunteers fell ill with what it called "clinical signs consistent with inflammation in the central nervous system."
On Feb. 22, based on information obtained from sources close to the study, The Washington Post reported that the number of cases had increased to 12 – a number Elan declined to confirm or deny at the time. But yesterday the company said the toll had risen to 15. And although volunteers in the study will continue to be monitored, officials said, the company will no longer consider restarting the dosing.
Ivan Lieberburg, Elan's chief scientific and medical officer, said yesterday that the 15 people who had experienced problems were all alive and that most of them were responding to treatment. He said it is still not clear why they developed the complications, which had characteristics of encephalitis (inflammation of the brain) and meningitis (inflammation of the membranes surrounding the brain). No such symptoms had been seen in the earlier animal or human studies.
"We never saw a hint of this," Lieberburg said. "It came as a total shock to Elan."
Most of the victims became ill after getting their second injection, which was given about a month after the first, Lieberburg said. Symptoms typically appeared several weeks after that inoculation, he said, which is why the number of cases continued to expand even after the shots were halted in January.
Symptoms included stiff necks and low-grade fevers, which were difficult to distinguish from ordinary flu, Lieberburg said. Some mild confusion was also noted – a common finding in Alzheimer's patients and a trait often exacerbated during periods of even benign illness.
"It's disappointing, obviously," said Steven DeKosky, chairman of neurology and director of the Alzheimer's Research Center at the University of Pittsburgh, who was briefed on the results by Elan officials yesterday. However, DeKosky said, there is still good reason to hope that similar products in the pipeline will prove effective, but with fewer side effects.
The vaccine was designed to stimulate an immune system attack against protein deposits that accumulate in the brains of Alzheimer's victims. Those so-called beta amyloid deposits are widely suspected of being the underlying cause of the memory-robbing disease, which affects 2 million to 4 million mostly elderly people in this country.
Experts familiar with the vaccine have theorized in recent days that the vaccine may have stimulated too powerful an immune reaction in the brain. Lieberburg theorized that some people may be genetically more susceptible to such an overreaction. One possible way around that problem, he and others said, would be to inject precise doses of beta amyloid antibodies into the body, instead of leaving it up to the body's immune system to produce those antibodies.
"It may be the end of this particular product, but not for this immunological approach overall," said William Thies, vice president of medical and scientific affairs at the Alzheimer's Association.
Lieberburg emphasized that while this vaccine, known as AN1792, will not be tested any longer in people, the company still has many other promising experimental Alzheimer's products at various stages of development.
"We feel very, very positive about this program," Lieberburg said. "We're committed to continuing this work."
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