Dimebon Development for Alzheimer's Officially Dead

Medivation and partner Pfizer will cease development of Dimebon (latrepirdine), a now thoroughly defunct antihistamine, "for all indications and will terminate the ongoing open label extension study in Alzheimer's disease." The small biopharm company announced the official end of Dimebon development yesterday in a press release, and the story was picked up by the WSJ. Dimebon's demise is based on flat results in the companies' CONCERT trial, a phase 3 study in which Dimebon was assessed as add-on treatment to symptomatic treatment donepezil (Aricept) in patients with mild-moderate AD.

Previous news on Dimebon (March 2010) was that it failed to improve cognition or global functioning in a placebo-controlled phase 3 study of patients with AD, and Medivation's share price plummeted 30 points on the dated news. In 2008, Pfizer agreed to pay Medivation $225 million upfront and another $500 million when Dimebon was FDA approved. The agreement—which split development costs and potential profits on a 60-40 basis (Pfizer assumed the larger share)—also conferred licensing rights to Pfizer for use of the drug in Huntington's disease. But Dimebon also disappointed in this devastating condition.

Pfizer was evidently betting on the chance that Dimebon would sail through US clinical development, given very favorable phase 2 results published in The Lancet in July of 2008.  In a randomized, double-blind, placebo-controlled, multicenter study (N = 183) that was conducted entirely within Russia and funded by Medivation, patients with mild-moderate AD who received Dimebon demonstrated significantly less cognitive decline at 6 months, as measured by the ADAS-cog (mean score difference, 4.0; P < .0001). Although some were scratching their heads as to why an antihistamine would have a disease-delaying or merely symptomatic effect in AD. The ultimate, tired lesson: promising phase 2 results are not a harbinger of anything, except chancy phase 3 study.

Medivation reminds us that it's also developing an investigational drug (MDV3100) with Astellas for the treatment of advanced prostate cancer. The compound is in the phase 3 stage, and Medivation got a huge bump in its stock price in late October just before news of very favorable survival data was publicly released.