West Coast Editor

On the same day that academic researchers said red wine might help prevent Alzheimer's disease, Wall Street raised a toast to Medivation Inc.'s results with Dimebon, which hit all five endpoints in a Phase II trial against the condition.

San Francisco-based Medivation's stock (AMEX:MDV) closed Thursday at $8.30, up $2.25, or 37.2 percent.

"We literally got the last top-line data less than 24 hours ago," David Hung, president and CEO of the San Francisco-based firm, told investors during a conference call, declining to speculate about a partner, although he said the company's general strategy is to sell products or partner them beyond Phase II.

Whether Dimebon protects neurons, Hung said, has yet to be shown. "We can hope, but we have to prove that in more rigorous clinical studies," he said.

An antihistamine used since 1983 in Russia (where the Phase II study was conducted at 11 sites in 183 patients), Dimebon has proven that it also binds to cholinesterase and the NMDA receptor - known targets in treating Alzheimer's.

Compared with patients given placebo, those given Dimebon (dimebolin) demonstrated highly statistically significant improvement on the study's primary efficacy endpoint, the Alzheimer's Disease Assessment Scale-cognition, ending up with a 4-point improvement in the mean change from baseline to the 26th week, as compared to placebo (p< 0.0001). Results proved strong as well on the key secondary efficacy endpoint, the Clinical Global Impression of Change, with a 0.6-point improvement in the mean change from baseline to the 26th week compared to placebo (p< 0.0001).

Dimebon-treated patients also gained statistically significant improvement (p<0.01) compared with placebo patients on all three of the other secondary efficacy endpoints - the Activities of Daily Living, the Neuropsychiatric Inventory and the Mini Mental State Examination.

Dimebon-treated patients reached statistically significant improvement over baseline on all five efficacy endpoints used in this study (p<0.05), whereas placebo patients deteriorated.

The drug was well tolerated, with fewer serious adverse events in Dimebon-treated patients than placebo. No gastrointestinal side effects except for dry mouth appeared in more than 3 percent of the Dimebon-treated patients, and dry mouth occurred in only 13.5 percent of those given the drug.

Aricept (donepezil), an acetylcholinesterase inhibitor from Tokyo-based Eisai Co. Ltd. (partnered with Pfizer Inc., of New York), is the world's leading therapy for Alzheimer's disease, but can bring diarrhea, nausea and vomiting, lasting one week to three weeks, especially with the 10-mg/day dose. But Aricept has an edge over other therapies because such side effects are said to be less, and Dimebon might be able to beat Aricept in that regard as well as efficacy.

"Obviously, [the Phase II trial] didn't compare Dimebon to other drugs on the market," said Lynn Seely, chief medical officer for Medivation, repeating that the data are "hot off the press, and we certainly haven't had any time to do subpopulation analysis," either.

Marketed compounds for Alzheimer's in the same class as Aricept include Reminyl (galantamine hydrobromide, from UK-based Shire Pharmaceuticals Group plc); Exelon (rivastigmine tartrate, from Novartis AG, of Basel, Switzerland); and Cognex (tacrine, from First Horizon Pharmaceutical Corp., of Alpharetta, Ga.).

Currently available Alzheimer's drugs bring other unpleasant side effects. Cognex has been linked to liver toxicity in some patients, and Aricept - which holds the largest portion of the estimated $1.7 billion U.S. market - may cause muscle cramps and fatigue.

Medivation also said a higher percentage of Dimebon patients than placebo-treated subjects finished the trial (87.6 percent and 81.9 percent, respectively), for an overall trial completion rate of 84.7 percent.

As of April 30, the company had about $20.2 million in cash and short-term investments. Medivation expects to enter the clinic with Dimebon in Huntington's disease and with another compound in prostate cancer in "the near future," Hung said.

Its small-molecule compounds for prostate cancer, known as the MDVN 300 series, were discovered by Charles Sawyers, Peter Bing and a medical investigator at the University of California in Los Angeles. Medivation acquired them in the fall of 2005.

Officials have not yet spoken with the FDA about the Dimebon Alzheimer's data and don't know if trials outside Russia will be required - tablets used in the latest trials were made by a Russian company licensed by the government there - but in any case, Seely said the latest results should "help us in enrolling that [Huntington's] study more quickly."

Formerly known as Orion Acquisition Corp. II (incorporated in 1995), Medivation gained its current name last year, when the company's employee roster listed five full-time staffers.

The red wine study directed by Mount Sinai School of Medicine found that moderate consumption in the form of cabernet sauvignon may help reduce the incidence of the disease. Results will appear in the November 2006 issue of The FASEB Journal, a publication by the Federation of American Societies for Experimental Biology.