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Hopes Dashed for Yet Another Alzheimer's Therapy

Alzheimer's researchers—not to mention patients and families—have faced a long string of disappointments in recent years as one promising treatment after another has failed to stop or slow the disease. The latest blow came yesterday as Pfizer and its partners announced that they are suspending development of the intravenous form of bapineuzumab after it failed to improve mental or physical function in 1300 patients with mild to moderate Alzheimer’s disease.

Bapineuzumab is an antibody that targets β amyloid, a protein fragment that accumulates in the brains of Alzheimer's patients and is widely thought to be a key culprit in the disease process. Despite encouraging evidence from animal studies that it clears amyloid from the brain, when it came to clinical improvements in human patients the drug proved no better than placebo in two phase III clinical trials.

The first trial, announced in July, showed no benefit in 1100 people with a genetic variant that increases the risk of Alzheimer's. The second trial, announced yesterday, showed no benefit in people without this genetic variant.

"I wouldn't describe it as a surprise, but it's a disappointment for sure," says John Hardy, an Alzheimer’s researcher at University College London. "These companies have spent an enormous amount of time on this particular antibody." There are a number of reasons why the trials may have failed, Hardy says, including the possibility that the antibody did not have high enough affinity for the particular forms of amyloid that do the most damage in the brain, or that the patients in the trials had already experienced too much brain degeneration to benefit.

Clinical trials expected to begin early next year will put the latter possibility to the test in people with genetic mutations that cause an early-onset form of Alzheimer’s disease. Participants in their 30s and 40s will receive antiamyloid drugs years before symptoms would be expected to appear. Bapineuzumab could still be considered for those trials, among other options.

Results from a phase III trial with another antibody that targets β amyloid—solanezumab, developed by Eli Lilly—should be announced later this year. "Undoubtedly, this is worrying for the Lilly antibody," Hardy says of the bapineuzumab results. But he says he hasn't given up hope that the Lilly trial will produce better results. Solanezumab has different molecular characteristics than bapineuzumab, and it's conceivable it does a better job clearing harmful forms of amyloid from the brain, Hardy says.

Despite this latest setback, Samuel Gandy, an Alzheimer’s researcher at the Mount Sinai School of Medicine in New York City, says he’s more optimistic than ever that scientists will eventually figure out how and when to lower β amyloid in order to stave off dementia. "I think that controlling one's amyloid β is likely to be a lifelong endeavor just like controlling one's cholesterol," Gandy says.