Alzheimer's researchers have faced a series of frustrations in recent years as one promising compound after another has flopped in late-stage clinical trials. Unfortunately, the string continues with the announcement today that another closely watched trial—for a drug called dimebon—has failed.
Dimebon was something of a dark horse. An antihistamine introduced in Russia in 1983, it turned up in a screen for potential Alzheimer's drugs and led to a clinical trial that yielded remarkably encouraging results: In 2008, researchers reported in The Lancet that 78 people with mild to moderate Alzheimer's disease who took dimebon showed significant improvements in memory and cognition, as well as the ability to carry out the activities of daily life.
The new study was led by Medivation, a San Francisco, Californai-based biopharmaceutical company, and Pfizer (which reportedly paid $225 million to license the drug). It enrolled 598 patients with mild to moderate Alzheimer's. This time, there were no significant differences between the dimebon and placebo groups. "The results ... are unexpected, and we are disappointed for the Alzheimer's community," Medivation's president and CEO, David Hung, said in a statement.
Some researchers who study the mechanisms of Alzheimer's aren't surprised, however. "I think a lot of us have been saying the same thing ... that it looks too good to be true, but let's hope not for the sake of patients," says Harvard University's Rudolph Tanzi. From the beginning, it was never clear why an antihistamine would protect the brain from Alzheimer's disease, Tanzi and others say. "There wasn't a single bit of published data on the mechanism of action," says Sam Sisodia of the University of Chicago in Illinois. Several possible explanations had been floated, Sisodia says, but in his view the drug's actions weren't understood well enough to justify a trial. "Just throwing drugs into people just because you have an idea it might work is illogical," he says.