Alzheimer's Drug Shows Progress

While not an all-out success, Phase II testing of a Wyeth-Elan treatment showed positive results in a subset of patients. Investors applauded

The much anticipated results of a clinical trial of one of the more promising Alzheimer's drugs, released June 17, were mixed at best. But in the Alzheimer's world that qualifies as a success—and on Wall Street, it was a winner as well.

Wyeth Pharmaceuticals (WYE) and Elan Corp. (ELN) announced that the Phase II trial of their jointly developed drug, bapineuzumab, did not attain statistically significant results in the overall group of 240 patients. But in a subset of patients that lacked a high-risk gene variant for the disease, the drug significantly improved symptoms in five different tests. Patients in the gene-free group also lost less brain volume.

Investors chose to read the trial as a positive, boosting Elan's share price by 2.89, or 10.7%, to 30. The stock hit a six-year high of 30.30 during the day's trading. Wyeth's shares rose by 2.08, or 4.8%, to 45.16.

Targeting the Amyloid Protein

The gene in question, APOE4, is carried by about half of all Alzheimer's patients and usually signals earlier onset of the disease. A drug that might help only those patients without the gene may not sound all that meaningful, but the 18-month trial marks one of the first hints of success in the search for a drug meant to change the course of the disease for which there is currently no treatment.

The four drugs approved so far for Alzheimer's treat only symptoms, and work only for a few months. The bapineuzumab trial also represents one of the first successes for a number of drugs in the pipeline that are trying to modify the disease by clearing away a brain-destroying protein called amyloid that is a hallmark of Alzheimer's.

If the results play out in a much larger Phase III trial already under way—and that is still a big if—then bapineuzumab would represent a major advance in one of the greatest unmet needs in medicine.

A Potential Multibillion-Dollar Market

"It's fair to say that both myself and the other investigators on this trial are quite excited," says Dr. Anton Porsteinsson, director of the Alzheimer's disease care, research, and education program at the University of Rochester, who is treating patients in both the Phase II and III trials of the drug. "It is the first time a study of meaningful size and scope has shown that beta amyloid modulation makes a difference."

Wall Street's enthusiasm reflects the multibillion-dollar market that any successful Alzheimer's drug could tap into. The Centers for Disease Control and Prevention announced last week that in 2006, the last year for which data were compiled, Alzheimer's moved up from the seventh to the sixth leading cause of death in the U.S. There are currently 5.2 million Americans living with the disease, and the Alzheimer's Association expects that number to increase to 9 million by 2020. One in 10 people over 65 develop the brain-destroying disease; over age 85, the odds rise to one in two.

Most pharmaceutical analysts had not expected statistically significant results from the Wyeth-Elan trial because of the relatively small number of patients. Brian McCarthy, a biotech analyst with Merriman Curhan Ford, said the results were encouraging, however, because the patients in the non-APOE4 group showed improvement across a broad spectrum of tests.

Out of Failure, Some Success

This could still end up being a statistical fluke however, if the overall number of patients in the non-APOE4 group turns out to be very small. "We want to take a look at the full test results before reaching any conclusions, but this subset analysis is certainly very interesting," McCarthy said. Wyeth and Elan will present the full results at the International Conference on Alzheimer's Disease in Chicago at the end of July.

Bapineuzumab is an antibody, given by injection, that grew out of one of the more spectacular drug failures of recent years—a therapeutic vaccine meant to alter the course of Alzheimer's. The vaccine was also developed by Elan and Wyeth, and was once considered the most promising drug in the pipeline against the dreaded disease. But in 2002 the trial had to be stopped because several patients developed a deadly swelling of the brain.

A year later, after some trial participants had died of Alzheimer's, autoposies revealed that those patients who received the vaccine had much lower levels of amyloid in their brains, a sticky plaque that destroys neurons. Although there is no definitive proof that amyloid is the cause of Alzheimer's, the evidence that the vaccine did what it was supposed to gave the two companies reason to pursue a drug that would attack amyloid without the vaccine's side effects.

Elan and Wyeth said that bapineuzumab, also known as AAB-001, did cause some brain swelling in the Phase II trial. To minimize this danger, the drug is being administered at a lower dose in the Phase III trial, which started last year.