18 January 2012. Another Phase 3 trial of Dimebon has fallen flat. In the multicenter CONCERT trial, patients with mild to moderate Alzheimer’s disease who took 5 or 20 mg of Dimebon three times per day for 12 months, on top of the cholinesterase inhibitor donepezil, fared no better than those taking donepezil and a placebo. This is according to a statement released yesterday by Pfizer and Medivation, company sponsors of the drug. Primary outcome measures were cognition and activities of daily living. The companies will halt their collaboration to develop and market Dimebon, according to the press release. In 2008, Pfizer, the maker of donepezil, agreed to pay Medivation at least $725 million for worldwide rights to Dimebon, based on certain regulatory milestones. Pfizer assumed 60 percent of Dimebon development costs and paid Medivation $225 million up front.
“The results were not unexpected, but there was a tiny part of me that was still hoping it would pan out, mostly for the sake of all the families who volunteered for the study,” wrote Murali Doraiswamy, Duke University Medical Center, in an e-mail to Alzforum. Doraiswamy was one of the CONCERT investigators. “The big question is to see if we can learn anything postmortem about why the drug looked so good in the first trial,” added Doraiswamy. Investigators had initially reported that Dimebon improved cognition in a Phase 2 trial conducted in Russia (see ARF related news story). In the U.S., the drug failed in prior Phase 3 trials for AD (see ARF related news story) and, most recently, Huntington’s disease patients (see ARF related news story).
“My biggest worry is that this is going to make investors even more gun shy about this field,” wrote Doraiswamy. That concern has dogged the field ever since a flood of negative trial results began pouring in. Promising anti-inflammatory drugs, Aβ immunotherapies, γ-secretase inhibitors, DHEA, and a Rage inhibitor, to name a few, have all come up short so far.—Tom Fagan.