25 September 2002. Forest Laboratories, Inc., reported last week that patients with moderate to severe Alzheimer's disease taking memantine and donepezil had significant improvement over patients on donepezil alone on tests of cognitive and daily functioning. The phase III trial will be submitted to the FDA, which is considering Forest's July 2002 New Drug Application for memantine in the treatment of moderate to severe AD.
Memantine has been used in Germany for over a decade to treat cognitive symptoms of dementia, as well as Parkinson's disease and coma, and was approved for marketing in the European Union in late May 2002. (See related news item, including comments by Richard Harvey.) In contrast to donepezil and other cholinesterase inhibitors, memantine--an NMDA receptor antagonist--is thought to boost cholinergic function by protecting cholinergic neurons from toxic overstimulation by glutamate.
Forest said that their six-month, randomized, double-blind, placebo-controlled trial of 403 patients showed that memantine significantly improves cognitive performance (as measured by the Severe Impairment Battery) and daily function (as measured by the AD Cooperative Study Inventory - Activities of Daily Living scale). They note that most other treatments of AD have merely slowed cognitive decline, as opposed to actually improving symptoms from baseline level.
The company intends to release the results of three further Phase III trials next year, including studies of the drug's effectiveness in earlier stages of AD.—Hakon Heimer