Here's the corresponding FRX PR:
JAMA Reports Alzheimer's Patients Treated With Combination of Namenda(TM) (Memantine HCl) and Donepezil Experienced Significant Benefits Compared to Donepezil Alone
FOREST LABORATORIES LOGO
Forest Laboratories Inc.
NEW YORK, NY USA 10/11/2000
NEW YORK, Jan. 20 /PRNewswire-FirstCall/ -- Forest Laboratories, Inc.
(NYSE: FRX) announced today that a study published in the current issue of the
Journal of the American Medical Association (JAMA) concludes that combining
Namenda(TM) (memantine HCl) with a stable dose of donepezil, a commonly
prescribed Alzheimer's drug, provides greater cognitive, functional, global,
and behavioral benefits to people with moderate to severe Alzheimer's disease
than treatment with donepezil alone. The results of this study mark the first
time that positive results have been observed when using a combination of two
drugs for the treatment of Alzheimer's disease. While the results of this
trial have been previously presented at major medical meetings around the
world, their publication in JAMA represents the first time these results have
been published in a peer-reviewed journal.
(Logo: newscom.com )
Namenda, now available in the United States, is the first and only
medication approved to treat the moderate to severe stages of Alzheimer's
disease. All other approved treatments, including donepezil, belong to a
class of drugs called acetylcholinesterase inhibitors (AChEI) that are
indicated for patients in the mild to moderate stages of Alzheimer's. Because
Namenda has a unique mechanism of action that is different from the
acetylcholinesterase inhibitors, the availability of Namenda makes its use in
combination with donepezil a possibility for the treatment of moderate to
severe Alzheimer's disease.
"The study published today is a source of excitement and hope for the
Alzheimer's community," said study lead investigator Pierre Tariot, M.D.,
Professor of Psychiatry, Medicine and Neurology at the University of
Rochester. "The results clearly show that patients with moderate to severe
Alzheimer's disease treated with the combination of Namenda and donepezil
perform better on measures of intellectual and daily functioning compared to
those patients taking donepezil and a sugar pill."
Study Design
This ground-breaking, six-month study included 404 patients at 37 sites
and was the first prospective, double-blind, placebo-controlled, Phase III
trial to evaluate the benefits of dual therapy with Namenda and donepezil in
patients with moderate to severe Alzheimer's disease. All patients were
treated with donepezil for a minimum of six months and were required to
receive a stable dose of donepezil for at least three months in order to enter
the study. Patients were then randomized to receive donepezil plus 20mg per
day of Namenda, or donepezil and placebo. The study was designed to measure
cognition and function as primary outcomes, while global status and behavioral
symptoms were measured as secondary endpoints.
Positive Results Seen In All Measures: Cognition, Global Status,
Function, and Behavior
Patients receiving the combination of Namenda and donepezil experienced an
improvement in cognition relative to baseline while patients receiving
donepezil and placebo declined relative to their baseline status. The
difference between these two groups was statistically significant (p=0.001).
Cognition was measured via the Severe Impairment Battery (SIB). This test,
designed especially for people with moderate to severe dementia, enables
researchers to gather direct performance-based data related to a wide variety
of tasks, such as writing simple words or using a cup and spoon.
Researchers also observed significantly less decline in activities of
daily living (p=0.028) as assessed by the Alzheimer's Disease Cooperative
Study Activities of Daily Living Inventory, modified for severe dementia
(ADCS-ADLsev). The findings suggest that people on the combination of Namenda
and donepezil may be able to perform basic activities necessary for
independence and personal care -- such as dressing and bathing to a greater
extent than patients taking donepezil alone. Patients treated with
Namenda/donepezil also performed better in an assessment of global status,
based on the Clinician's Interview-Based Impressions of Change-Plus (CIBIC-
Plus) compared to the study's control group (p=0.03). According to the
Neuropsychiatric Inventory (NPI), a scale used to assess behavioral effects,
patients treated with Namenda/donepezil exhibited fewer behavioral
disturbances, with less severity as compared to patients treated with
donepezil alone (p=0.002).
"The study is especially significant because it is the first
placebo-controlled trial to show efficacy in patients with moderate to severe
Alzheimer's disease when treatments with different mechanisms of action are
used together," said Lawrence S. Olanoff, M.D., Ph.D., Executive Vice
President, Forest Laboratories. "Additionally, patients treated with Namenda
and donepezil performed significantly better than patients on donepezil alone
with respect to cognition and daily functioning. While Namenda's efficacy as
a monotherapy has been demonstrated by other large-scale studies, this study
supports its clinical utility when used in combination with the
acetylcholinesterase inhibitor, donepezil."
In general, the incidence of treatment-emergent adverse events was similar
in patients treated with Namenda/donepezil and the placebo/donepezil
combination. A significantly greater percent of patients in the
Namenda/donepezil group (85 percent vs. 75 percent) completed the study
compared to the placebo/donepezil group (p=0.011).
About Namenda
Namenda (memantine HCl), approved on October 16, 2003, by the U.S. Food
and Drug Administration, is indicated for the treatment of moderate to severe
Alzheimer's disease. Namenda is the first of a new class of medications,
called NMDA (N-methyl-D-aspartate)-receptor antagonists, to treat Alzheimer's
disease with a mechanism of action distinct from other currently available
drugs. Namenda is administered orally at a recommended dose of 10mg twice
daily following a four-week titration.
In all clinical trials, Namenda has been safe and well tolerated. Namenda
is contraindicated in patients with known hypersensitivity to memantine HCl or
to any excipients used in the formulation. The most common adverse events
reported with Namenda vs. placebo (> or = 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.
Namenda is available in pharmacies in both a 4 week Titration Pak and 5mg
and 10mg tablets. Interested parties can get more information on Namenda and
obtain the prescribing information by logging on to namenda.com or by
calling 1-877-2-NAMENDA (1-877-262-6363).
Namenda's Mechanism of Action
Namenda is a low to moderate affinity NMDA-receptor antagonist. It is
thought that overexcitation of NMDA receptors by the neurotransmitter
glutamate may play a role in Alzheimer's disease. Glutamate plays an integral
role in the neural pathways associated with learning and memory. The
excitotoxicity produced by abnormal levels of glutamate is thought to be
responsible for neuronal cell dysfunction observed in Alzheimer's disease.
Namenda is thought to selectively block the excitotoxic effects associated
with abnormal transmission of glutamate, while allowing for the physiological
transmission associated with normal cell functioning.
Alzheimer's Disease
Alzheimer's is a progressive disease of the brain and it is the most
common type of dementia. The term dementia is used to describe the progressive
loss of cognitive, intellectual, or functional abilities. Published reports
project that by 2010 more than 5.1 million people in the United States will
have Alzheimer's disease. Currently, all Alzheimer's medications approved in
the United States other than Namenda belong to a class of agents called
acetylcholinesterase inhibitors, which are indicated for patients with mild to
moderate symptoms of the disease. The progressive nature of Alzheimer's
disease means that most patients who suffer from it will move through all the
stages, including the moderate to severe stages. Namenda will be of use to
patients from the time their disease has reached the moderate stage through
progression into and throughout the severe stages. |
