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| METABOLEX ANNOUNCES FINAL PHASE 2 RESULTS DEMONSTRATING METAGLIDASEN IMPROVES BLOOD GLUCOSE CONTROL IN TYPE 2 DIABETES PATIENTS WITHOUT CAUSING WEIGHT GAIN OR EDEMA
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Data Presented During Oral Session at ADA Scientific Sessions – Abstract #44-OR |
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San Diego,
(June 10, 2005): Metabolex, Inc. today announced final results from its randomized, double-blind, placebo-controlled Phase 2 clinical trial of its lead investigational drug
metaglidasen, a novel oral insulin sensitizer. Results of the multi-center trial showed that metaglidasen significantly reduced hemoglobin A1c (HbA1c), the gold-standard measure of a patient’s 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 (fluid retention) 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 (an insulin-sensitizing hormone that is reduced in both type 2 diabetes and obesity). The data were presented in an oral session at the American Diabetes Associations’ 65th Scientific Sessions by Julio Rosenstock, M.D., a Phase 2 study investigator at the Dallas Diabetes and Endocrine Center.
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| “These exciting results demonstrate that metaglidasen treats insulin resistance, one of the major underlying causes of type 2 diabetes, and improves glycemic control without increasing body weight or increasing the risk of edema, unlike the currently marketed insulin sensitizers. Clearly, further study is warranted,“ said Dr. Rosenstock, a practicing endocrinologist at Medical City Dallas and a clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas. “An effective medication with a better clinical safety profile would be a real advance for people with diabetes, helping them adhere to and benefit from their therapy.“ |
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| Phase 2 Study Design and Results |
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The trial involved 217 patients with type 2 diabetes on concomitant insulin therapy who had inadequate control of blood glucose. These patients are at the highest risk of edema and weight gain from the use of insulin sensitizers. All patients remained on their insulin dose and were randomized to receive either 200 mg or 400 mg of metaglidasen or placebo once daily for 12 weeks. The study was conducted at 29 centers in the United States and Mexico. Final Phase 2 trial results showed:
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Efficacy Findings |
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A statistically significant reduction in HbA1c in patients taking both doses of metaglidasen compared with the placebo group taking only insulin (0.9% and 1.0% from baseline for metaglidasen 200 mg and 400 mg, respectively, and 0.3% for placebo, p=0.002). |
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A statistically significant dose-dependent decrease in fasting blood glucose. The decrease in patients taking metaglidasen 400 mg compared with placebo was 41 mg/dL (p=0.005). |
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A 21% reduction in triglyceride levels in patients taking metaglidasen 400 mg compared with placebo. |
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A statistically significant dose-dependent reduction in uric acid in patients taking metaglidasen 200 mg (-7.5%, p=0.002) and 400 mg (-20%, p<0.001) compared with both baseline and placebo. |
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A statistically significant dose-dependent increase in adiponectin levels in patients taking metaglidasen 200 mg (p=0.018) and 400 mg (p<0.001) compared with placebo. |
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Safety Findings |
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Both doses of metaglidasen were well tolerated and had no significant effect on liver and muscle enzymes, kidney function or hematopoietic parameters. |
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No increase in the incidence of edema with metaglidasen (the incidence of edema was 11.0% for 200 mg and 7.2% for 400 mg compared with 20.0% for the placebo group taking only insulin; p=0.037, two-sided trend test). |
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Tolerability Findings |
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No evidence of weight gain with metaglidasen compared with insulin alone (0.6 kg increase for 200 mg and 400 mg versus 1.3 kg increase for placebo). |
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“We believe that metaglidasen will improve the treatment of type 2 diabetes by controlling glucose and lipid levels without the tolerability issues associated with currently marketed products and become a best-in-class drug,“ said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. “We are currently evaluating patients in a second Phase 2 trial of metaglidasen at a higher dose as part of our clinical development program to develop next-generation insulin sensitizers, and are actively planning for the Phase 3 program.“ |
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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, comprising 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. The company is also developing MBX-2044, a follow-on compound with a similar profile, which has completed a Phase 1 clinical trial. |
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About Diabetes |
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| 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. 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, oral therapies and insulin injections. |
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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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| Abstract #44-OR
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| MBX-102: A Novel Non-TZD Insulin Sensitizer that Improves Glycemic Control without Causing Edema or Weight Gain in Patients with Type 2 Diabetes (T2DM) on Concomitant Insulin Therapy. Julio Rosenstock, MD, Fernando Flores-Lozano, MD, Sherwyn Schwartz, MD, Guillermo Gonzalez-Galvez, MD and David B Karpf, MD. To be presented on Friday, June 10, 2005, at 4:45 p.m. PDT during the “Monotherapy for Type2 Diabetes” oral session at the American Diabetes Associations’ 65th Scientific Sessions in San Diego. |
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