Alzheimer's Vaccine Trial Halted
Study suspended after volunteers experience brain inflammation
FRIDAY, Feb. 22, 2002 (HealthDayNews) --The trial of the first vaccine for Alzheimer's disease has suffered an unexpected, and potentially fatal, setback.
Elan Corp, an Irish company testing the compound, suspended its trial over concerns that the injection is causing severe brain inflammation.
The experimental vaccine, AN-1792, is designed to provoke an immune reaction to amyloid beta plaques, the hard protein clusters whose buildup in the brain is believed to cause Alzheimer's. Tests on mice reportedly had suggested that the vaccine could slow or even prevent development of the dementia disease.
The biotech firm first revealed trouble with the vaccine in a Jan. 17 press release posted on the company's Web site and distributed to reporters over the Internet. At the time, the company said it had stopped administering the vaccine after four study volunteers in France developed "central nervous system" inflammation.
However, the Washington Post reported today that eight more study volunteers had fallen ill after receiving the vaccine. The newspaper cited unnamed sources saying the inflammation appears to be either encephalitis or meningoencephalitis, potentially life-threatening swelling of the brain or of the membrane that surrounds the brain.
In a statement issued last month, the company said virus particles had been detected in the spinal and brain fluid of some of the first four study volunteers to become ill. "However," it continued, "the cause of the inflammation remains to be determined."
"Our decision to temporarily suspend further dosing, pending the results of our evaluation, is a standard approach to protect the safety of patients in clinical trials," Dr. Ivan Lieberburg, Elan's chief scientific and medical officer, said in the statement. "A decision will be made on resumption of dosing pending the outcome of this investigation."
Virginia Lee, an Alzheimer's expert at the University of Pennsylvania in Philadelphia, said that the trial's troubles seem to have appeared from nowhere.
"In animals, all the data have been very, very interesting and very positive," Lee said today, adding that the vaccine's initial human safety study turned up no inflammatory reactions. But, she noted, "anything that you generate from an animal model, you really never know how well it will work in humans."
Lee continues to believe Elan's approach is a sound one. However, she said, the vaccine in principle, and now apparently in practice, has the potential to aggravate the immune system, which she called the "worst-case scenario" for such a compound.
Elan and its American partner, Wyeth-Ayerst Laboratories, a division of American Home Products Corp., said roughly 360 people with Alzheimer's have received the vaccine, which was being tested at clinics in four European countries and at almost a dozen sites in the United States.
Trial coordinators at several sites contacted today referred all inquiries to Elan.
However, one clinic researcher, speaking on a condition of anonymity, said some of the adverse reactions involved volunteers in the United States.
William Thies, vice president of medical and scientific affairs at the Alzheimer's Association, said Elan's initial report in January left room to wonder if the problem might have been isolated to the French center. But the additional eight cases occurred at other sites, suggesting the reactions are probably due to the vaccine itself, he said.
If that's the case, Thies added, the trial is unlikely to resume.
Max Gershenoff, an Elan spokesman, today called the Post report "old news," and said all the cases have been reported to the U.S. Food and Drug Administration, European regulators and an independent review committee monitoring the trial.
Gershenoff said the company has also notified the sick volunteers' physicians about their condition, "in accordance with good clinical practice."
Scientists are working on other forms of Alzheimer's vaccines. The experiments include using partial fragments of amyloid protein to arouse the immune system and proteins, called antibodies, generated in that response.
"We have this unanswered question of whether the progress of Alzheimer's can be limited by decreasing the accumulation of amyloid in the brain," Thies said. "Until we answer that fundamental question, we are still going to have a lack of complete enthusiasm for doing clinical trials in the amyloid area."
Thies said the Elan trial was furthest along in this effort, and he called its stumble "extremely disappointing."
What To Do
Alzheimer's disease affects an estimated 4 million Americans, a number projected to hit 15 million by the middle of this century, according to the Alzheimer's Association.