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Dementia Prevention Conference
Is Flurizan the Alzheimer’s Treatment the World
Awaits?
Studies so far have shown modest results, new study
underway
June 21, 2005 – The media jumped all over the news
from the Dementia Prevention Conference about a possible treatment for
Alzheimer’s disease with the drug R-flurbiprofen (Flurizan) which is
entering a Phase III clinical trial. The results so far, however, have
been only mildly successful with the headlines on the Phase II study
being “Flurizan Phase II Trial Shows No Overall Benefit.” Still, there
is hope for this beta-amyloid altering drug being developed by Myriad
Pharmaceuticals.
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The Amyloid Hypothesis |
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The "amyloid hypothesis" states that Alzheimer's
disease is initiated by the production, aggregation and
deposition of the toxic amyloid beta (Aβ) peptide leading to
disruption of cell-to-cell communication and eventually to the
death of neurons in the brain.
The amyloid hypothesis remains the predominant
scientific explanation for the cause of Alzheimer's disease and
is the culmination of more than a decade of scientific research
from around the world.
It has been discovered that the amyloid precursor
protein, APP, is cleaved first by an enzyme called beta-secretase
and is then cut into smaller fragments (amyloid peptides) by a
second enzyme called gamma-secretase. These amyloid peptides are
of several different lengths that have differing properties.
Accumulation of the longer 42 amino acid form of this peptide
(Aβ42) causes cell death in the brain and initiates the
formation of plaques, whereas shorter forms of the amyloid
peptide are less toxic and do not initiate plaque deposits.
Some approaches to Aβ42 reduction have been to
block the activity of the gamma-secretase enzyme with drugs
called "gamma-secretase inhibitors." This has led to safety
concerns because many other essential proteins throughout the
body are normally processed by gamma-secretase.
In contrast to the gamma-secretase
inhibitor approach, Myriad scientists have pursued a different
strategy to lowering Aβ42 production and have selected the
investigational compound Flurizan based on its ability to act as
a modulator, rather than an inhibitor, of the gamma-secretase
enzyme in cultured human cells and in animal models.
Insight as to how Aβ42 may be implicated in
Alzheimer's disease is the result of remarkable progress in
Alzheimer's research that has occurred over the last two
decades. Clinical trials are currently being conducted to
develop drugs that will hopefully lead to disease-modifying
therapies for this devastating disease.
Short movie
on amhyloid hypothesis - Click |
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Facts About Alzheimer's |
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Dementia is an umbrella term for many conditions,
including Alzheimer's. Increasing age is currently considered
the greatest risk factor for Alzheimer’s, with one in 10 of
senior citizens over 65 and almost half of those over 85
affected. An estimated 4.5 million Americans have Alzheimer’s,
which is twice as many as in 1980. By 2050, without gains in
prevention, there could be as many as 16 million with the
disease. Research has suggested it is the disease most feared by
baby boomers and senior citizens. |
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Phase II trial shows that treatment with R-flurbiprofen
(Flurizan) did not help individuals with mild or moderate Alzheimer’s
disease when results for all 207 participants were considered as a
whole, according to a report from Myriad, the drug’s developer.
However, the company says it saw some encouraging
signs when data for just the 128 participants with mild Alzheimer’s were
analyzed separately. Based on these preliminary results, Myriad plans to
move forward with a Phase III trial and is recruiting participants
throughout the United States.
In the Flurizan Phase III trial, about 100 U.S.
sites will enroll approximately 750 individuals with mild to moderate
Alzheimer’s disease. Participants will be randomly assigned to receive
400 or 800 milligrams of Flurizan twice daily or a placebo. The trial is
designed to determine whether those assigned to either dose of Flurizan
fare better in mental function or ability to carry out daily activities
than those on the placebo. Trial details are posted in the federal
online medical research database at
ClinicalTrials.gov.
"We are pleased to hear that Myriad is sufficiently
encouraged to go ahead with the Phase III trial," says William H. Thies,
Ph.D., Alzheimer’s Association vice president, medical and scientific
affairs. "R-flurbiprofen theoretically works by modifying beta-amyloid
processing in a different way than most other drugs currently in
clinical trials. It would be a worthwhile contribution to clinical
knowledge to see how this drug performs in a larger trial designed to
explore some of the early signs Myriad sees in their data.”
The company made a presentation of the details
about their Phase II results at the Alzheimer’s Association
International Conference on Prevention of Dementia in yesterday.
According to Myriad, the Phase II participants
with mild Alzheimer’s who were taking the highest experimental dose of
R-flurbiprofen showed a tendency to do better than those receiving the
placebo on tests of memory and thinking skills, ability to carry out
daily activities and overall function. However, those benefits did not
meet statistical criteria for having a high likelihood of being due to
the effects of the drug rather than to chance.
The company then further subdivided the data to
focus on participants with mild Alzheimer’s taking the highest dose who
also developed high levels of the drug in their bloodstream. That group
experienced a statistically significant benefit in their ability to
carry out daily activities and their overall function, but not on
measures of memory and thinking skills.
Flurbiprofen is one of a handful of nonsteroidal anti-inflammatory drugs
(NSAIDs) shown in laboratory and animal studies to reduce levels of
beta-amyloid, a protein fragment considered a prime suspect in
Alzheimer’s disease.
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Story Updates |
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Ispronicline Joins Effort to Find Alzheimer’s Cure
July 6, 2005 – There is a new kid on the block in
the mad race to find a cure for Alzheimer’s disease and dementia.
Ispronicline is now enrolling participants for a Phase II study after
clinical studies in which elderly people taking Ispronicline performed
better on memory and attention measures than those taking a placebo.
Read more...
Alzhemed Resumes Race for Alzheimer’s Cure with
Phase III Trial
July 5, 2005 – The Phase III clinical trial for
Alzhemed, a drug battling Flurizan for the top spot in Alzheimer’s
treatment research, is ready to begin in North America. Neurochem, Inc.,
the manufacturer, announced today the recruitment of 950 patients with
mild-to-moderate Alzheimer’s Disease for the trial to be conducted in 51
U.S. and 17 Canadian clinical centers.
Read more...
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Generic flurbiprofen is a mixture of "R" and "S"
molecules whose structures are mirror images of one another. Myriad’s
Flurizan, also known by the investigational name MPC-7869, contains only
R-flurbiprofen, the form that seems to have the greatest impact on beta-amyloid
but has little or no anti-inflammatory effect. The anti-inflammatory
effects of NSAIDs are associated with certain serious side effects,
including bleeding in the stomach and intestines and increased risk of
heart attack and stroke.
What the market thinks
In March, Decision Resources, Inc., one of the
world's leading research and advisory firms focusing on pharmaceutical
and health care issues, forecasts that the launches of Neurochem's
Alzhemed and Myriad Genetics' Flurizan will be major factors in driving
the market for the treatment of Alzheimer's disease to more than double
to $4 billion by 2013.
According to the new Pharmacor study entitled
Alzheimer's Disease, a dramatic change in market dynamics will begin
half way through the study's 2003 to 2013 forecast period, as the first
disease-modifying therapies—including Alzhemed (NC-531) and Flurizan (R-flurbiprofen)—enter
the market. These two therapies will account for more than 56% of
Alzheimer's disease treatment sales in the United States, Western Europe
and Japan.
"Acetylcholinesterase inhibitors (AChEIs) will
continue to dominate the Alzheimer's disease market until 2008, with the
defining trend during this period being a shift in market share among
competing AChEIs," said Michelle Grady, analyst at Decision Resources.
"Eisai/Pfizer's Aricept (donepezil) will retain its
leadership position, as Shire/Janssen's Reminyl (galantamine) and, to a
lesser extent, Novartis's Exelon (rivastigmine) gain market share.
However, sales of these drugs will decline during the second half of the
study period because of the expiry of their patents. All agents in this
class will lose patent protection by 2013."
With the commercial launch of the biomarker
Pittsburgh Compound B and the availability of disease-modifying drugs
during the second half of the forecast period, the study also finds that
physicians will begin diagnosing Alzheimer's disease earlier in the
progression of the illness.
For more information, please see:
More news reports on Alzheimer's at
SeniorJournal.com
Details about the new Phase III trial of Flurizan
at
ClinicalTrials.gov
A Jan. 19, 2005,
Research News feature on the Phase III Flurizan trial
An Aug. 5, 2003,
Research News feature on R-flurbiprofen
The Alzheimer’s Association
fact sheet on the "amyloid hypothesis" and drugs targeting beta-amyloid
The Alzheimer’s Association
fact sheet on anti-inflammatory drugs
Click to More Senior News on the
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