Patients with mild to moderate Alzheimer’s disease who were treated with the experimental drug Dimebon from US drugmaker Medivation Inc, showed improvement in key mental skills after a year compared to patients who took the placebo. The patients on the active drug showed clear improvements in memory, language, awareness of time and place, and a more complex process called “praxis”, which means having an idea and then actually putting it into practice.

The findings of the pivotal phase III trial were presented yesterday, Thursday, at the 60th Annual Meeting of the American Academy of Neurology (AAN) that has been taking place in Chicago all this week and finishes tomorrow, Saturday 19th April.

The presenter was Dr Steven H Ferris, the Gerald J and Dorothy R Friedman Professor of Psychiatry at New York University (NYU) and director of the NYU Alzheimer’s Disease Center. According to US News and World Report, Ferris describes his connection to the study as that of an “external scientific advisory board” member to the drugmaker. His job is to interpret the findings and help plan future studies; he has no equity in the company.

Ferris described the improvement observed in the patients who took Dimebon as “broad” as opposed to “selective”, because it spanned improved memory, orientation, language and praxis.

“This is an important finding given that deficits in memory and thinking are one of the hallmarks of Alzheimer’s disease and cause patients and caregivers significant distress,” said Ferris.

To measure cognitive function, the study investigators used a standardized measure based on that used by the US Food and Drug Administration (FDA) to approve drugs currently prescribed for mild to moderate Alzheimer’s disease.

The measure is called the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), from which 11 sudomains were assessed at the start, and then every three months of the one year study.

The results showed that:

  • After one year, the patients who received the active drug improved on 9 of the 11 ADAS-cog subdomains, compared with those on placebo.

  • The cognitive functions that showed improvement included: memory, orientation, the ability to copy simple drawings, the ability to carry out a familiar but complex sequence of actions, and language.

  • Improvements in memory included: word recall, word recognition and remembering instructions.

  • Improvements in language included: overall language, following commands, naming objects, finding words, and comprehension.

Chief medical officer of Medivation, Dr Lynn Seely, said in a press statement that:

“We have recently presented a number of different findings from our first pivotal trial of Dimebon at scientific conferences, demonstrating that this investigational drug has a beneficial impact on the key aspects of Alzheimer’s disease; from behavioral symptoms to thinking and memory problems to impairments in daily function.”

The company said it is pressing forward as rapidly as it can to develop Dimebon as a treatment for mild to moderate Alzheimer’s disease.

An earlier 12-month, double blind, placebo controlled trial involving 193 patients had already shown that patients on Dimebon showed statistically significant improvements in memory, thinking, daily living activities, behaviour and overall clinical function, compared with patients on placebo.

According to the drugmaker, the improvements were already showing after 12 weeks, and were sustained after six months and a year. Also, at the six month point, the patients on the drug showed significantly better function on all five aspects of the disease than they did at the start of the trial.

The drugmaker is planning to start a second confirmatory pivotal phase III trial soon, after which it will apply for US and European marketing approval in 2010, said the company in a press statement.

The drug is also being evaluated as a treatment for Huntington’s disease.

Source: Medivation press release, US News and World Report.

Written by: Catharine Paddock, PhD