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| METABOLEX'S
INVESTIGATIONAL TREATMENT FOR TYPE 2 DIABETES MEETS PRIMARY
AND SECONDARY ENDPOINTS IN PHASE 2 TRIAL |
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| Metaglidasen Exceeds Target
Profile by Showing Efficacy Comparable to Current Treatments
without Causing Edema or Weight Gain |
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MONTE CARLO, Monaco
and HAYWARD, Calif., (March 22, 2005): Metabolex,
Inc. today announced that Phase 2 clinical trial results for
its lead product candidate metaglidasen, a novel, oral insulin
sensitizer, showed that it met the study's primary endpoint
of reducing hemoglobin A1c (HbA1c) in patients with type 2
diabetes. The proof-of-principle trial demonstrated that metaglidasen
had comparable efficacy to currently marketed insulin sensitizers
without causing the dose-limiting side effects of edema and
weight gain often experienced by patients on those drugs.
The secondary endpoints of lowering triglycerides and uric
acid were also met. The trial results were presented today
at the 3rd International Symposium on PPARS Efficacy and Safety
in Monte Carlo.
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| “These clinically meaningful
data are highly encouraging and merit further study to demonstrate
that an insulin sensitizer can be effective in treating patients
with type 2 diabetes without posing safety and tolerability
issues,” said Mayer B. Davidson, M.D., Professor of Medicine
UCLA School of Medicine and Director, Diabetes Program, King-Drew
Medical Center. “By providing comparable efficacy to currently
approved products without the usual side effect profile, metaglidasen
has the potential to improve the treatment of type 2 diabetes
and become a best-in-class drug.” |
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In the Phase 2 trial
of metaglidasen, results showed a statistically significant
reduction in HbA1c (1.0% from baseline and 0.7% vs
placebo for patients taking the 400 mg dose of metaglidasen,
p=0.002), the gold-standard measure of a patient's
blood glucose control. This reduction is comparable
to that observed with currently marketed compounds.
The study also showed a significant reduction in fasting
blood glucose (33 mg/dL from baseline and 41 mg/dL
vs placebo for patients taking metaglidasen 400 mg,
p = 0.014). Importantly, there was no increase in
edema versus insulin alone; in fact, there appeared
to be a significant dose-dependent decrease in the
risk of edema in patients treated with metaglidasen
(p=0.026). Results also showed no increase in weight
with metaglidasen compared with placebo, exceeding
expectations. Plans for Phase 3 clinical trials of
metaglidasen are currently underway.
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“Insulin sensitizers
are important because they treat insulin resistance - the
underlying cause of type 2 diabetes,” said David B.
Karpf, M.D., Chief Medical Officer of Metabolex and Clinical
Associate Professor of Medicine at Stanford University School
of Medicine. “To have a drug that addresses insulin
resistance without causing the typically observed side effects
of weight gain and edema, which should also predict a lower
risk of congestive heart failure, would be a significant advance
in the treatment of this common and often debilitating disease.”
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| Novel
Approach to Insulin Sensitizers |
Insulin sensitizers, with
worldwide sales of nearly $4 billion, represent an attractive
treatment option for type 2 diabetes because they target insulin
resistance, the underlying cause of the disease, and may preserve
pancreatic beta-cell (the source of insulin) function. However,
currently marketed insulin sensitizers carry a warning of
increased risk of congestive heart failure due to edema (fluid
retention). These drugs also can cause significant weight
gain, which can compromise patient compliance. |
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Metaglidasen (formerly MBX-102),
the lead candidate in Metabolex's clinical development program,
has a chemical structure and method-of-action that differentiates
it from insulin sensitizers currently on the market. Metaglidasen
modulates the genes needed for insulin sensitization, but
not those responsible for edema and weight gain. The company
is also developing MBX-2044, a follow-on compound with a similar
profile that recently completed a Phase 1 clinical trial.
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| Metaglidasen Phase
2 Study Design |
| The randomized, double-blind, placebo-controlled
study of metaglidasen involved 217 patients with type 2 diabetes
on concomitant insulin therapy who had inadequate control of
blood glucose. These patients are considered to be at the highest
risk of edema and weight gain from the use of insulin sensitizers.
All patients remained on their stable insulin dose and were
randomized to receive either placebo, 200 mg of metaglidasen,
or 400 mg of metaglidasen daily for 12 weeks. The study was
conducted at nearly 30 centers in the United States and Mexico. |
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| Both doses of metaglidasen were well tolerated
and showed no effect on liver and muscle enzymes, kidney function,
or hematopoietic parameters. |
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| Harold E. Van Wart, Ph.D., Metabolex's President
and CEO, will be presenting these data and providing an overview
of the company's research and development efforts for the treatment
of type 2 diabetes at the Advances in Diabetes Treatment Conference
in London on March 24, 2005 at 10:20 a.m. London Time. |
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| About Diabetes |
| Type 2 diabetes is a disease characterized
by insulin resistance, in which the body does not properly use
insulin, the hormone that converts glucose into energy. According
to the American Diabetes Association, it is the sixth leading
cause of death in the United States and affects about 18.2 million
people, while about 41 million people in the U.S. are prediabetic.
Most people with diabetes have type 2, or adult-onset, diabetes
and the incidence is expected to rise to 10 percent of the population
by the year 2010. In Europe, the number of people with diabetes
totals more than 33 million. The World Health Organization predicts
that number will rise to 47 million by 2030. Globally, diabetes
affects 171 million people. |
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| The cause of diabetes is unknown, although
genetics and environmental factors such as lack of exercise
and obesity appear to play a role. Treatment includes dietary
changes, insulin injections, and oral therapies. |
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| About Metabolex |
Metabolex is a privately
held biotechnology company dedicated to the discovery and
development of novel therapeutics to transform the treatment
of diabetes and related metabolic disorders. Metabolex has
drawn on its deep understanding of diabetes to create the
largest database of genes involved in diabetes and to build
a rich pipeline of product candidates and drug discovery targets.
The company's clinical program is focused on developing next-generation
insulin sensitizers that lower blood glucose without the serious
safety and tolerability issues associated with currently marketed
products. |
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| For additional information about
Metabolex and its development pipeline, visit www.metabolex.com. |
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