Forest Laboratories Inc., of New York, reported at the American Academy of Neurology meeting in Honolulu that the drug memantine enhanced cognitive function in moderate to severe Alzheimer's disease patients when treated in combination with Aricept (donepezil).

Combination therapy was shown to improve patients' cognition relative to baseline and as compared to the donepezil/placebo arm of the trial. Separate research also demonstrated memantine's long-term efficacy when used as a single agent. The combination results have been presented before at a closed meeting, though single-agent data results from an open-label extension of a study were published in the current New England Journal of Medicine.

The six-month, Phase III, randomized, placebo-controlled combination study involved 402 moderate to severe Alzheimer's patients at 37 U.S. sites. Data showed that patients treated with memantine and donepezil illustrated a sustained improvement in cognitive function over baseline as measured by the Severe Impairment Battery index. But cognitive function for patients on donepezil and placebo declined relative to their baseline status - a statistically significant difference (p=0.001) in favor of the memantine/donepezil combination.

Patients taking the combination therapy also showed significantly less decline in activities of daily living (p=0.028), according to another index, the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, modified for severe dementia. A new drug application was filed at the end of last year for memantine, which Forest has developed in partnership with Neurobiological Technologies Inc., of Richmond, Calif., and Merz Pharmaceuticals GmbH, of Frankfurt, Germany. The drug is a moderate-affinity, uncompetitive N-methyl D-aspartate receptor antagonist that modulates glutamate levels. (See BioWorld Today, Dec. 23, 2002.)

In other news at the conference, separate studies on Aricept pointed to further positive findings. Already approved for mild to moderate Alzheimer's disease, data suggest that the cetylcholinesterase inhibitor also may benefit patients at more advanced stages of the disease. Findings from a 145-patient study pointed to significant improvement in global function, cognition, behavior and activities of daily living vs. placebo. The data, previously published in the August 2001 issue of Neurology, demonstrated that Aricept provided significant benefits vs. placebo in everyday tasks, as well as in behavioral symptoms associated with the disease.

Additional data suggested Aricept's use outside of treating Alzheimer's. Data showed it may benefit patients with vascular dementia, a disease caused by a single, localized stroke or series of strokes for which there are no approved therapies. A supplemental new drug application for Aricept, marketed by Eisai Inc., a subsidiary of Tokyo-based Eisai Co. Ltd., and New York-based Pfizer Inc., is under FDA review for the vascular dementia indication.

Other data from two separate studies supported Aricept's potential use in treating two other dementia-related illnesses beyond Alzheimer's disease. Findings showed that treatment improved cognition in patients with mild cognitive impairment and behavioral symptoms in patients with Parkinson's-related dementia.