http://www.washingtonpost.com/wp-dyn/articles/A48989-2002Feb21.html
Test of
Alzheimer's Vaccine Is Halted
12 Volunteers Said to Be Seriously Ill With
Brain Inflammation
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By Rick Weiss
Washington Post Staff Writer
Friday, February 22, 2002; Page A01
The vaccine, made by the Irish pharmaceutical company Elan and known by its
code name AN-1792, had generated unusually intense enthusiasm among scientists
and patient advocates during the past two years, as experiments in mice
suggested it could halt the progression of Alzheimer's and perhaps even cure
the deadly disease.
Alzheimer's gradually robs people of their minds. It affects 2 million to 4
million elderly Americans and is expected to affect 15 million by 2030. Even
the best treatments today have a very modest impact.
Taking an unprecedented immunologic approach to treating a brain disease,
the vaccine aims to elicit an immune system attack against "beta
amyloid," the brain protein believed to be at the root of Alzheimer's.
Although animal studies and early human safety studies suggested the vaccine
was reasonably safe, the strategy was controversial. Immune reactions typically
cause inflammation, and inflammation in the brain can cause serious problems or
death.
Company officials have released few details about the problems. A spokesman
said an independent committee is reviewing data from the study, which has
enrolled about 360 people with mild to moderate Alzheimer's in four European
countries and 11 U.S. sites.
But sources familiar with the study, including some who have been in contact
with Elan officials, said there is little question the vaccine triggered the
brain reactions, which some called encephalitis (an inflammation of the brain)
and another called "meningoencephalitis," an inflammation of the
brain and surrounding membranes.
Both syndromes can cause symptoms ranging from fever, headache and vomiting
to altered consciousness, muscle weakness and seizures.
Some scientists had warned that the vaccine might trigger such complications
or even exacerbate Alzheimer's, a disease some believe is caused by natural inflammatory
processes.
One such critic, Trey Sunderland, chief of the geriatric psychiatry branch
at the National Institute of Mental Health, said yesterday that the vaccine may
have caused the encephalitis in volunteers directly or it may have caused a disruption
of blood vessels in the brain. That would allow viruses or other infectious
agents to enter and cause encephalitis.
Elan, which is developing the vaccine with Wyeth, a pharmaceutical division
of American Home Products Corp. of Madison, N.J., would not say yesterday how
quickly it had halted inoculations after the first few patients were diagnosed.
The company also would not say what, if any, information was being shared with
other volunteers who might be at ongoing risk of encephalitis.
A company spokesman said only doctors at individual test sites could speak
to that issue, but officials at several sites yesterday said they had been told
by the company not to talk to reporters.
Even when things go well, experts said, clinical trials involving people
with cognitive deficits pose extraordinary challenges to the notion of
"informed consent" -- the requirement that volunteers be made aware
of all the risks of a study and of any changes in those risks during the course
of a study.
An Elan spokesman yesterday said the company "follows all appropriate
clinical standards to ensure the well-being of all patients in studies and is
working closely with their physicians." All those who experienced ill
effects "have been treated and are responding appropriately," said
the spokesman, who refused to characterize their health further.
The company first mentioned the emerging problem Jan. 18, in a low-profile
"update" posted on its Web site. In the second paragraph of the
update, the company noted that four patients in the high-profile study had
"clinical signs consistent with inflammation in the central nervous
system," and that further dosing of patients in the multicenter
international trial had been "temporarily suspended." It did not say
when the diagnoses were first made.
Since then, the number has climbed to 12, at several test sites, according
to sources in contact with Elan officials. One of those, William Thies, vice
president of medical and scientific affairs at the Alzheimer's Association,
said he still believes the general approach of immunotherapy for Alzheimer's
has a promising future, though details of the vaccine might have to change.
Elan has said it is developing products that are similar to AN-1792 but more
refined.
"I think everyone is puzzled" about why the problems happened,
said Marilyn Albert, an Alzheimer's researcher at Massachusetts General
Hospital, who heads the Alzheimer's Association's medical and scientific
advisory council. But in all likelihood, Albert said, "they can't go
forward with this formulation."
It is the second major setback for Elan this month. The company announced
earlier that certain officers and directors were being sued by shareholders
alleging violations of U.S. securities laws, and that the company was under
investigation by the Securities and Exchange Commission.
© 2002
The Washington Post Company
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