New Study Results Demonstrate Beneficial Effects of Axura® (Memantine) on Brain Activity in Patients with Mild to Moderate Alzheimer’s Disease

Frankfurt am Main, April 28th, 2004 – Results from a U.S. positron emission tomography (PET) imaging pilot study with memantine show that the treatment with Merz’ Alzheimer’s drug Axura® reverses the metabolic decrease in the brain of patients with mild to moderate Alzheimer’s disease. The data were presented today at the American Academy of Neurology (AAN) Annual Meeting in San Francisco by Prof. Steven G. Potkin, University of California.

In the mild to moderate stages of Alzheimer’s disease, a decrease in cerebral glucose metabolism is often associated with progression of the disease. The PET study presented today, was conducted to analyze the effects of the uncompetitive NMDA-receptor antagonist Axura® on the metabolic changes in brains of Alzheimer patients in mild to moderate stages of the disease. The investigation of functional brain activity was conducted in conjunction with a large Phase III study in mild to moderate Alzheimer’s disease by Forest Laboratories, Merz’ strategic partner for the U.S. This study showed that Axura® treatment resulted in a cognitive stabilization above baseline and significant benefits in favor of memantine on global outcome compared to placebo.

“We are pleased that the results of the study demonstrate the efficacy of Axura® on brain activity in patients with mild to moderate Alzheimer’s disease. With these results and given the good tolerability of memantine, many more patients may be treated effectively in the future,” stated Dr. Hans J. Möbius, Chief Scientific Officer of Merz Pharmaceuticals.

Alzheimer’s disease is often characterized by a bilateral pattern of decreased metabolism, that is most prominent in temporal, parietal and prefrontal association areas. With [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) it is possible to measure regional metabolism in different brain areas. In early stages of Alzheimer’s disease the FDG-PET often demonstrates a decreased metabolism in widespread cortical areas. Increasing severity of dementia parallels a decline in glucose metabolic rate, which correlates with regional neuronal loss.

Study Design

The objective of this randomized, double-blind PET study was to assess the effects of memantine on regional cerebral glucose metabolism in patients suffering from mild to moderate Alzheimer’s disease. The PET scan was performed at baseline and after 24 weeks of treatment on five placebo-treated and five Axura® treated patients from the total population of 403 participants of the Phase III clinical trial investigating the efficacy of memantine (20 mg/d) versus placebo in early stages of Alzheimer’s disease.

Patients receiving Axura® demonstrated statistically significant increase in glucose metabolism in several regions of the brain associated with language and attention. On the other hand, placebo-treated patients showed the expected metabolic decline in several of the same regions. Obviously Axura® can reverse the Alzheimer’s brain-specific regionally defined metabolic decrease, which might correlate with neuronal activity. This finding is consistent with the results of the Phase III study, which demonstrated the clinical efficacy of Axura® in mild to moderate Alzheimer’s disease.

About Axura®

Axura® – patented and developed by Merz Pharmaceuticals – is the first in a new class of drugs against Alzheimer’s disease. Axura® has a unique mechanism of action targeting the glutamatergic pathway. It is the first drug which has been approved for moderate to severe Alzheimer’s Disease in the U.S. (October 2003), subsequent to the European approval in May 2002. In Germany memantine is marketed by Merz under the brand name Axura®. Merz has licensed the exclusive rights for memantine to Forest Laboratories for the United States, where it is available under the brand name Namenda™ since January 2004. H. Lundbeck A/S has acquired exclusive rights to a series of markets worldwide including Europe and co-marketing rights in other selected international markets. Lundbeck markets memantine under the brand name Ebixa™ in all their markets.