Shares of Medivation Inc. jumped 22.4 percent on 12-month data showing that its lead compound, Dimebon, preserved function and prevented progressive deterioration in Alzheimer's disease patients after one year of therapy.

Results from the Phase II study showed that Dimebon was five for five, reaching statistical significance across all study endpoints, including cognition, overall clinical function, activities of daily living and behavior. But perhaps most notable was the fact that the "effects shown at the end of one year were substantially greater than [results] at six months," David Hung, president and CEO of Medivation, said from the Alzheimer's Association meeting in Washington, where he's scheduled to present the one-year study results today.

Dimebon's six-month data, reported in September, were pretty impressive on their own. Compared with patients given placebo, those treated with Dimebon (dimebolin), an oral small molecule believed to bind to both cholinesterase and the NMDA receptor, showed 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). In comparison, the average ADAS-cog improvement for existing AD drugs is around 2.7 points, and studies of top-selling AD drug, Aricept (donepezil, Pfizer Inc.) showed improvement ranging from 2.7 points to 3 points. (See BioWorld Today, Sept. 22, 2006.)

One-year results for Dimebon were even better. Data showed an increased improvement in ADAS-cog score of 6.9 points over placebo for patients receiving Dimebon, meaning that the cognition score "increased at year-end, a time when most drug effects are diminishing," Hung told BioWorld Today. AD is known as a steadily progressive disease - those on placebo showed a decline of about 5.5 points on the ADAS-cog scale - yet patients receiving Dimebon "were at the same level of function as they were when the trial began. I'm not aware of any other drug that has shown that."

The news also was encouraging to Wall Street. Medivation's stock (NASDAQ:MDVN) climbed $3.62 Monday to close at $19.80.

The Phase II trial enrolled 183 patients with mild to moderate AD and originally was intended to involve a six-month randomized, placebo-controlled design following a six-month open-label study. But Medivation opted to continue with the placebo arm to obtain more clear-cut efficacy data. A total of 120 patients completed 12 months of treatment, with the dropout rate comparable between the Dimebon and placebo arms.

In addition to the ADAS-cog scale, the Phase II study also measured global function endpoint using the Clinician's Interview-Based Impression of Change with a caregiver interview (CIBIC-plus). Results showed Dimebon's benefit over placebo at 0.8 points at 12 months, and global function improved or remained stable in 69 percent of treated patients after one year. Medivation's drug also produced an improvement over placebo on the Alzheimer's Disease Cooperative Study Group-Activities (ADCS-ADL) scale (5.2 points vs. 2.9 points), as well as benefits measured by the Mini Mental State Exam (MMSE) and Neuropsychiatric Inventory (NPI).

On the safety side, Dimebon exhibited much fewer gastrointestinal side effects than the marketed cholinesterase inhibitors, such as Aricept. Excluding instances of dry mouth, GI effects occurred at a rate of less than 3 percent, Hung said. That suggested the drug's mechanism of action might "not primarily be cholinesterase inhibition," he added, which means that there's potential for Dimebon in combination with cholinesterase inhibitors. Medivation likely will explore combination treatment in future studies.

Right now, the focus is on an upcoming Phase III registrational program for Dimebon, expected to begin in 2008. The company has not yet disclosed the trial design, but Hung said the AD drug approval pathway is "extremely well-trodden" so "we know exactly what the FDA is looking for. We're pushing to the finish line as fast as we can," with expectations for a regulatory filing in 2010.

Medivation owns all rights to Dimebon and has refrained from entering a partnership to date, though "we've gotten a lot of interest" Hung said, and likely will sign a partner when "we can get the greatest value for shareholders."

In the meantime, the company is "well capitalized," he added. It ended the first quarter with $43 million in cash and short-term investments and that should be enough "to get us into Phase III in both Alzheimer's and Huntington's disease."

Medivation currently is testing Dimebon in a Phase I/IIa trial in collaboration with the Huntington Study Group.