March 03, 2010 -- Dimebon, a once-promising new Alzheimer's drug from Pfizer Inc., may be no more effective than a placebo at treating the disease, according to late-stage clinical data released by the company Wednesday.
But while this news comes as a shock to many and a disappointment to all in the Alzheimer's community, some experts say the game's not over yet for Dimebon.
"The need for new therapies is huge and we should not be daunted by a single failed trial," says Dr. Pierre Tariot, associate director of the Banner Alzheimer's Institute. "The field…is littered with examples of trials that fail to show benefit even with drugs that work and are FDA approved. From my perspective, the drug needs to be studied further."
Dimebon raised hopes in the Alzheimer's community after a 2008 study of the drug in Russia suggested it was more effective than other Alzheimer's treatments on the market. As the drug has an excellent safety profile, the potential for the drug was high, says Dr. Richard Lipton, director of Montefiore Headache Center.
o when this new Dimebon study, called the CONNECTION trial, failed to reproduce the Russian results, it came as a huge letdown experts say.
"This is yet another major disappointment," says Dr. Steven Ferris, executive director of the Aging & Dementia Research Center at New York University. "Despite general skepticism about the previous Russian study, these totally negative results are very unexpected."
But other experts said the failure was no big surprise. "If it looks too good to be true, it probably is," says Dr. Rudolph Tanzi, director of the Genetics and Aging Research Unit at Massachusetts General Hospital, referring to the positive results found in the 2008 Russian study.
Dr. Sid Gilman, chair of the Department of Neurology at the University of Michigan, similarly expected the trial to fail, saying that the Russian study results were dubious and that "basic science underlying the function of this drug is so poor."
One leading expert in Alzheimer's -- who wished to remain anonymous -- went so far as to say that there "was never any biological plausibility for this drug" and that "it is inconceivable to me that the FDA would approve this drug."
Currently, Pfizer is running four other late stage trials of Dimebon, including one involving Huntington's disease. No announcements have been made by Pfizer as to the fate of these trials but if they are positive, the drug still may be a candidate for FDA approval.
It's Not Over Until the FDA Sings
But do such clearly negative results close the door on Dimebon as a treatment for Alzheimer's?
Despite widespread doubt in the future of this drug, some experts felt that it was too soon to dismiss its therapeutic value altogether given the pressing need for better Alzheimer's drugs.
The current study, done in partnership with Medivation, Inc. was designed to show Dimebon's effects on thinking and overall function for those with mild-to-moderate Alzheimer's. Since Dimebon works through a different mechanism than standard Alzheimer's drugs, researchers hope that it would be able to be used in conjunction with other therapies.
While the negative result from the CONNECTION trail could simply mean that Dimebon does not work, says Lipton, it is also possible that the studies used the wrong doses of the drug or gave the doses too infrequently or at the wrong stage of the disease.
Dr. Samuel Gandy, professor of Alzheimer's disease research at Mount Sinai School of Medicine, adds that in light of other trials, such as one published recently in the Archives of Neurology, which find benefit for Huntington's with Dimebon, the negative results are "puzzling" but not necessarily condemning.
"A careful post mortem is in order before the coffin lid is closed," he says.
What's more, other Alzheimer's drugs currently on the market, like Namenda, also failed to show benefit in some of their clinical trials, says Murali Doraiswamy, Chief, Division of Biological Psychiatry at Duke University Medical Center. Doraiswamy is an investigator on another Medivation clincial trial of Dimebon called CONCERT.
He points out that as long as another trial of Dimebon proves positive, the FDA will most likely approve the drug.
Whether puzzling, unexpected, or disappointing, these negative results unfortunately mean that a promising treatment option may not pan out for patients, Lipton says, but as far as pharmaceutical development is concerned, it may be "the end of a chapter but the beginning of a new one."