FDA accepts sNDA filing to expand Namenda's indication to include treatment of mild Alzheimer's
NEW YORK, N.Y., November 15, 2004 -- Forest Laboratories announced that the FDA has accepted the filing of its supplemental New Drug Application (sNDA) to expand the indication of Namenda (memantine HCl) to include treatment of mild Alzheimer's disease. Namenda is currently available for the treatment of moderate and severe Alzheimer's patients, making it the only approved treatment in the U.S. for patients beyond the moderate stage of the disease. Under existing FDA procedures, Forest should receive an initial action letter from the FDA by the third quarter of 2005.
"Forest is pleased the FDA has accepted our application," said Lawrence S. Olanoff, M.D., Ph.D., Executive Vice President, Forest Laboratories. "If the FDA approves the expansion of Namenda's indication as a treatment for moderate to severe Alzheimer's to include the mild stage, Namenda could be the first treatment in the U.S. approved to treat all stages -- mild through severe -- of this progressive disease."
The sNDA filing includes data from three studies: two double-blind, placebo-controlled, studies of Namenda as monotherapy in mild to moderate Alzheimer's disease and one double-blind, placebo-controlled study of Namenda administered to patients already taking an acetylcholinesterase inhibitor.
Data from a U.S. clinical trial demonstrated that patients treated with Namenda performed significantly better than patients who received placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-cog) (p=0.003), a measure of cognitive function, and the Clinician's Interview-Based Impression of Change -- Plus version (CIBIC- Plus) (p=0.004), a global measure of a patient's overall status. The six- month study was conducted at 42 U.S. centers and included 403 patients with mild to moderate Alzheimer's disease. Namenda was well tolerated, with patients experiencing adverse events at overall rates that were comparable to those on placebo.
In a similar monotherapy study conducted by H. Lundbeck in Europe, also included in the sNDA filing, the difference in values for the primary endpoints, the ADAS-cog and the CIBIC-Plus, was statistically significant in favor of the Namenda treatment group versus the placebo group at multiple time points. Although numerical improvement was observed at week 24, statistical significance was not reached. The European study was conducted at 65 centers and included 470 patients with mild to moderate Alzheimer's disease. As in the U.S. trial, adverse event rates overall were similar for the two treatment groups.
In the third, double-blind, placebo-controlled study, Namenda was administered to patients with mild to moderate Alzheimer's disease currently also receiving acetylcholinesterase inhibitor therapy. After 24 weeks of treatment, the Namenda/acetylcholinersterase inhibitor group performed numerically better on measures of cognitive (ADAS-cog) and global function (CIBIC-Plus) than the placebo/acetylcholinersterase inhibitor group. However, statistical significance was not reached at end point. The co-administration of Namenda and acetylcholinesterase inhibitor therapy in mild to moderate Alzheimer's disease was found to be well tolerated based on this study.
Namenda (memantine HCl) is the first in a new class of medications with a unique mechanism of action that focuses on the glutamate pathway, a new target for the treatment of Alzheimer's disease. Indicated for the treatment of moderate to severe Alzheimer's disease, Namenda was approved by the FDA (October 2003) based on the results of three placebo-controlled studies, which demonstrated Namenda's efficacy either as monotherapy or when used in combination with another approved Alzheimer's disease drug. Results from two studies in the U.S. -- both in moderate and severe Alzheimer's patients -- have been published in The New England Journal of Medicine and The Journal of the American Medical Association. Results from the European study in nursing home patients were published in the International Journal of Geriatric Psychiatry.
Namenda (memantine HCl) is contraindicated in patients with known hypersensitivity to memantine HCl or any excipients used in the formulation. The most common adverse events reported with Namenda vs placebo (greater than or equal to 5% and higher than placebo) were dizziness, confusion, headache, and constipation. In patients with severe renal impairment the use of Namenda has not been systematically evaluated and is not recommended.
Source: Forest Laboratories
Posted: November 2004