Assistant Managing Editor

Coming off a positive end-of-Phase-II meeting with the FDA, Medivation Inc. is gearing up to start a 525-patient confirmatory Phase III trial with Alzheimer's disease drug Dimebon that, if successful, should enable the firm to submit a regulatory filing.

To gain approval in Alzheimer's the company is required to conduct two pivotal studies. The good news for Medivation is that the FDA agreed to allow a previously completed Russian study of Dimebon in 183 Alzheimer's patients to count as the first of those pivotal studies, provided that a significant portion of the trial sites are in the U.S.

"We could not have had a more positive outcome" from the FDA meeting, Medivation President and CEO David Hung told investors during a conference call. He added that the agency's acceptance of the previous trial "may have shortened our development timeline by as much as two to four years."

Medivation shares (NASDAQ:MDVN) jumped $1.85, or 12.5 percent, to close Monday at $16.70.

The San Francisco-based company conducted the earlier trial in Russia because Dimebon (dimebolin) already is marketed there as an antihistamine. Results from that study, reported at scientific conferences last year, show that patients treated with Dimebon, an oral, small molecule believed to bind to both cholinesterase and the NMDA receptor, had a statistically significant 4-point improvement in the mean change from baseline at week 26, as measured by the Alzheimer's Disease Assessment Scale - cognition (ADAS-cog), well above the average ADAS-cog improvement of 2.7 for existing AD drugs. One-year data yielded even more impressive results, with patients on Dimebon improving 6.9 points in ADAS-cog score over placebo, suggesting a potential disease-modifying effect. (See BioWorld Today, June 12, 2007.)

Many patients in the trial ended the study "better than they had started," Hung said.

The success of that earlier study means that company decided to change "as little as possible in the design of" the confirmatory Phase III, he added. Essentially, it will be the same design as the Russian trial, except for its global enrollment and the addition of a lower dosing arm to explore minimum effective dosing.

Medivation expects to start enrolling patients with mild to moderate Alzheimer's disease next quarter across sites in the U.S., Europe and South America. They will be randomized to one of three treatment groups - Dimebon 20 mg three dimes daily, Dimebon 5 mg three times daily or placebo - and will be evaluated at six months using ADAS-cog and the Clinician's Interview-Based Impression of Change plus caregiver interview (CIBIC-plus).

The trial will not be conducted under a special protocol assessment. Hung said the path for regulatory approval in AD is "well-trodden," with drugs including Aricept (donepezil) already on the market, adding that the company feels the FDA's guidance is clear.

Aricept, an acetylcholinesterase inhibitor, is sold by Tokyo-based Eisai Co. Ltd. and New York-based Pfizer Inc. Other competing AD drugs 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.

Medivation anticipates concluding the confirmatory Phase III for Dimebon in 2010, with a new drug filing to come later that same year, Hung said.

In addition to that study, the firm has plans to look at potential trials of Dimebon in combination with other treatments and in a more severe patient population, as well as studies evaluating the drug's ability to modify disease.

Medivation also is pursuing Dimebon in Huntington's disease and, last year, expanded patients enrollment in a Phase II trial to test the drug's effect after three months of dosing. The primary endpoint will be measured using the Unified Huntington's Disease Rating Scale and results are expected in the first half of this year.

Beyond Dimebon, Medivation's pipeline includes MDV3100, a selective androgen receptor modulator, which is in a Phase II trial in hormone-refractory prostate cancer. Top-line results from that study, which are designed to evaluate safety, pharmacokinetics and prostate-specific antigen levels, are expected later this year.

Pending positive results in Huntington's and prostate cancer, the company anticipates moving directly into Phase III studies in both those indications this year, Hung said.

In preparation for late-stage studies, Medivation secured a potential $100 million credit facility agreement with Azimuth Opportunity Ltd. in September, which it can draw down at its discretion in exchange for registered common stock. As of Sept. 30, the firm had cash and equivalents totaling $31.5 million. (See BioWorld Today, Sept. 11, 2007.)