Forest Laboratories Inc. said that based on a preliminary analysis of a recent study, memantine administered to patients receiving acetylcholinesterase inhibitor therapy for the treatment of mild to moderate Alzheimer's disease failed to demonstrate statistically significant differences on cognitive or global outcomes vs. placebo/acetylcholinesterase treatment.
The drug is being developed with Neurobiological Technologies Inc., of Richmond, Calif. Although a new drug application is on file with the FDA in moderate to severe Alzheimer's disease and Forest said the results would not affect the filing, both companies lost stock value on the news, with Forest's stock (NYSE:FRX) falling $7.32 Thursday, or 12.1 percent, to close at $53.29, and Neurobiological Technologies' stock (NASDAQ:NTII) dropping 87 cents, or 18.3 percent, to close at $3.88.
Forest said further analysis of the data is ongoing. In the mild to moderate AD patients, the memantine/acetylcholinesterase group did not show a change from baseline in cognitive function after 24 weeks of treatment, while the decline in cognitive function over time in patients treated with a placebo/acetylcholinesterease inhibitor was less than expected. The difference observed between the two treatment groups was not statistically significant.
There were no apparent safety concerns regarding the co-administration of memantine and the acetylcholinesterase inhibitors.
Memantine is a moderate-affinity N-methyl-D-aspartate receptor antagonist. It is believed, Forest said, that memantine selectively blocks the excitotoxic effects associated with abnormal transmission of glutamate, which plays a role in the neural pathways associated with learning and memory. The NDA for memantine in moderate to severe Alzheimer's disease was filed late last year. Forest had filed before, in July 2002, but voluntarily withdrew it in September to add data and make certain corrections. It anticipates receiving a response from the FDA in the moderate to severe setting by the end of 2003 and hopes to launch memantine by mid-2004. (See BioWorld Today, Dec. 23, 2002.)
Frankfurt, Germany-based Merz + Co. GmbH initially developed memantine for Parkinson's disease, and received European approval in the early 1980s before turning the drug to Alzheimer's disease. In the early 1990s, Neurobiological Technologies began studying the drug in neuropathic pain, eventually reaching an agreement with Merz for the companies to share profits from both indications. Merz has licensed to Forest U.S. memantine marketing rights and European sales rights to Copenhagen, Denmark-based H. Lundbeck A/S.
Memantine data have hurt the companies' stock before. In May, Forest reported that a pivotal trial in neuropathic pain in diabetics missed its primary endpoints. The news cut $3.97 off Neurobiological Technologies' stock that day, or 50.5 percent, and it closed at $3.89. Forest's shares lost $1.49 to close at $51.18.