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| METABOLEX ANNOUNCES PRESENTATION OF METAGLIDASEN PRECLINICAL DATA AT KEYSTONE SYMPOSIA SCIENTIFIC CONFERENCE |
Study Comparing Metaglidasen with Rosiglitazone Shows Potent Anti-Diabetic and Lipid-Lowering Activity with Metaglidasen Without Significant Body or Heart Weight Increases |
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Hayward, Calif.,
(September 8, 2005): Metabolex, Inc. today announced findings from a preclinical study comparing metaglidasen, a novel oral insulin sensitizer in clinical development for the treatment of type 2 diabetes, to rosiglitazone, a currently marketed insulin sensitizer. Results showed that metaglidasen has potent blood glucose and lipid-lowering effects without the side effects of weight gain and edema (fluid retention), which are often seen with currently marketed insulin sensitizers and can limit their use. The data will be presented at Keystone Symposia’s Scientific Conference on Tissue-Selective Nuclear Receptors in Breckenridge, Colo. on Wednesday, September 21, from 2:30 – 4:30 p.m. (abstract #110).
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| “Preclinical and clinical trial results to date have shown that metaglidasen improves blood glucose control and triglyceride levels without increasing body weight or causing edema,” said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. “Because of its unique mechanism of action as a selective partial PPAR-γ modulator, we believe that metaglidasen has the potential to improve the treatment of type 2 diabetes without the safety and tolerability issues associated with currently marketed insulin sensitizers. We are continuing to evaluate metaglidasen in an ongoing clinical development program.” |
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| Preclinical Study Results |
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In vitro adipocyte model systems directly comparing metaglidasen and rosiglitazone, a TZD (thiazolidinedione), showed that metaglidasen selectively modulates the activity of PPAR-γ in a manner that enhances insulin sensitization, but does not appear to modulate genes responsible for fatty acid uptake, synthesis and storage. These data suggest that metaglidasen acts as a selective partial PPAR-γ modulator that retains insulin sensitization but lacks potent adipogenic activity (the production or deposition of fat).
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| Animal studies comparing the efficacy and side effect profiles of various doses of metaglidasen and rosiglitazone administered daily for 51 days showed: |
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| Efficacy |
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Both metaglidasen and rosiglitazone, at all doses, significantly reduced fasting insulin levels. |
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Both metaglidasen and rosiglitazone improved lipid levels and increased adiponectin levels (an insulin-sensitizing hormone that is reduced in both type 2 diabetes and obesity). |
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Side Effect Profiles |
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Metaglidasen treatment did not lead to significant body weight increases at any dose, whereas rosiglitazone treatment led to significant dose-dependent increases in body weight. |
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Correspondingly, only minor increases in adipose (fat) tissue weights were observed with metaglidasen whereas large increases were observed with rosiglitazone. |
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Metaglidasen did not significantly change heart weight, whereas rosiglitazone caused increases in heart weight, suggesting that edema is induced in rosiglitazone-treated rats but not in metaglidasen-treated rats. |
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“These findings are important because they demonstrate that, with a selective partial PPAR-γ modulator, it is possible to increase insulin sensitivity without the side effects of weight gain and edema,” said Thomas A. Gustafson, Ph.D., vice president, Biology, of Metabolex, who will present the data at the Keystone Symposia meeting. “These data provide us with additional confidence in metaglidasen as a next-generation insulin sensitizer that provides comparable efficacy with the potential of an improved side effect profile.” |
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Metaglidasen: Novel Approach to Insulin Sensitizers |
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The only insulin sensitizers on the market today are from the TZD class, with worldwide sales of nearly $4 billion. These represent an attractive treatment option for type 2 diabetes because they target insulin resistance, the underlying cause of the disease, and may preserve the function of pancreatic beta-cells (the source of insulin). However, these drugs can cause significant weight gain and edema, compromising patient compliance. Furthermore, currently marketed insulin sensitizers carry a warning of increased risk of congestive heart failure due to fluid retention.
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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 TZD insulin sensitizers. Metaglidasen modulates the genes needed for insulin sensitization, but not those responsible for edema and weight gain. |
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Metaglidasen Phase 2 Results |
| Final results from Metabolex’s randomized, double-blind, placebo-controlled Phase 2 clinical trial of metaglidasen were presented during an oral session at the American Diabetes Association’s 65th Scientific Session in June 2005. Results of the multicenter trial showed that metaglidasen significantly reduced hemoglobin A1c (HbA1c), the gold-standard measure of blood glucose control in insulin-treated patients with type 2 diabetes. This reduction in HbA1c was comparable to that of the currently marketed insulin sensitizers without the dose-limiting side effects of edema or weight gain often experienced by patients taking those drugs. Metaglidasen also improved other metabolic parameters, including lowering fasting blood glucose, triglycerides and uric acid, and inducing a significant dose-dependent increase in adiponectin levels. |
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About Keystone Symposia |
Keystone Symposia, a non-profit organization, has a 35-year history of organizing high quality scientific conferences to connect the scientific community and accelerate discoveries that benefit society. |
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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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