metabolex

[Guest guest]

Data Presented During Oral Session at ADA Scientific Sessions Abstract #44-OR SAN DIEGO and HAYWARD, Calif., June 10 /PRNewswire/ -- Metabolex, Inc.today announced final results from its randomized, double-blind,placebo-controlled Phase 2 clinical trial of its lead investigational drugmetaglidasen, a novel oral insulin sensitizer. Results of the multi-centertrial showed that metaglidasen significantly reduced hemoglobin A1c (HbA1c),the gold-standard measure of a patient's blood glucose control, ininsulin-treated patients with type 2 diabetes. This reduction in HbA1c wascomparable to that of the currently marketed insulin sensitizers without thedose-limiting side effects of edema (fluid retention) or weight gain oftenexperienced by patients taking those drugs. Metaglidasen also improved othermetabolic parameters, including lowering fasting blood glucose, triglyceridesand uric acid, and inducing a significant dose-dependent increase inadiponectin levels (an insulin-sensitizing hormone that is reduced in bothtype 2 diabetes and obesity). The data were presented in an oral session atthe American Diabetes Associations' 65th Scientific Sessions by JulioRosenstock, M.D., a Phase 2 study investigator at the Dallas Diabetes andEndocrine Center. "These exciting results demonstrate that metaglidasen treats insulinresistance, one of the major underlying causes of type 2 diabetes, andimproves glycemic control without increasing body weight or increasing therisk of edema, unlike the currently marketed insulin sensitizers. Clearly,further study is warranted," said Dr. Rosenstock, a practicing endocrinologistat Medical City Dallas and a clinical professor of medicine at the Universityof Texas Southwestern Medical Center in Dallas. "An effective medication witha better clinical safety profile would be a real advance for people withdiabetes, helping them adhere to and benefit from their therapy." Phase 2 Study Design and Results The trial involved 217 patients with type 2 diabetes on concomitantinsulin therapy who had inadequate control of blood glucose. These patientsare at the highest risk of edema and weight gain from the use of insulinsensitizers. All patients remained on their insulin dose and were randomizedto receive either 200 mg or 400 mg of metaglidasen or placebo once daily for12 weeks. The study was conducted at 29 centers in the United States andMexico. Final Phase 2 trial results showed: Efficacy Findings -- A statistically significant reduction in HbA1c in patients taking bothdoses 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). -- A statistically significant dose-dependent decrease in fasting bloodglucose. The decrease in patients taking metaglidasen 400 mg compared withplacebo was 41 mg/dL (p=0.005). -- A 21% reduction in triglyceride levels in patients taking metaglidasen400 mg compared with placebo. -- A statistically significant dose-dependent reduction in uric acid inpatients taking metaglidasen 200 mg (-7.5%, p=0.002) and 400 mg (-20%,p<0.001) compared with both baseline and placebo. -- A statistically significant dose-dependent increase in adiponectinlevels in patients taking metaglidasen 200 mg (p=0.018) and 400 mg (p<0.001)compared with placebo. Safety Findings -- Both doses of metaglidasen were well tolerated and had no significanteffect on liver and muscle enzymes, kidney function or hematopoieticparameters. -- No increase in the incidence of edema with metaglidasen (the incidenceof edema was 11.0% for 200 mg and 7.2% for 400 mg compared with 20.0% for theplacebo group taking only insulin; p=0.037, two-sided trend test). Tolerability Findings -- No evidence of weight gain with metaglidasen compared with insulinalone (0.6 kg increase for 200 mg and 400 mg versus 1.3 kg increase forplacebo). "We believe that metaglidasen will improve the treatment of type 2diabetes by controlling glucose and lipid levels without the tolerabilityissues associated with currently marketed products and become a best-in-classdrug," said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. "Weare currently evaluating patients in a second Phase 2 trial of metaglidasen ata higher dose as part of our clinical development program to develop next-generation insulin sensitizers, and are actively planning for the Phase 3program." Novel Approach to Insulin Sensitizers The only insulin sensitizers on the market today are from the TZD class,with worldwide sales of nearly $4 billion. These represent an attractivetreatment option for type 2 diabetes because they target insulin resistance,the underlying cause of the disease, and may preserve the function ofpancreatic beta-cells (the source of insulin). However, these drugs can causesignificant weight gain and edema, comprising patient compliance.Furthermore, currently marketed insulin sensitizers carry a warning ofincreased risk of congestive heart failure due to fluid retention. Metaglidasen (formerly MBX-102), the lead candidate in Metabolex'sclinical development program, has a chemical structure and method-of-actionthat differentiates it from TZD insulin sensitizers. Metaglidasen modulatesthe genes needed for insulin sensitization, but not those responsible foredema and weight gain. The company is also developing MBX-2044, a follow-oncompound with a similar profile, which has completed a Phase 1 clinical trial. About Diabetes Type 2 diabetes is a disease characterized by insulin resistance, in whichthe body does not properly use insulin, the hormone that converts glucose intoenergy. According to the American Diabetes Association, it is the sixthleading cause of death in the United States and affects about 18.2 millionpeople, while about 41 million people in the U.S. are prediabetic. Mostpeople with diabetes have type 2, or adult-onset, diabetes and the incidenceis expected to rise to 10 percent of the population by the year 2010.Globally, diabetes affects 171 million people. The cause of diabetes is unknown, although genetics and environmentalfactors such as lack of exercise and obesity appear to play a role. Treatmentincludes dietary changes, oral therapies and insulin injections. About Metabolex Metabolex is a privately held biotechnology company dedicated to thediscovery and development of novel therapeutics to transform the treatment ofdiabetes and related metabolic disorders. Metabolex has drawn on its deepunderstanding of diabetes to create the largest database of genes involved indiabetes and to build a rich pipeline of product candidates and drug discoverytargets. The company's clinical program is focused on developing next-generation insulin sensitizers that lower blood glucose without the serioussafety and tolerability issues associated with currently marketed products. For additional information about Metabolex and its development pipeline,visit http://www.metabolex.com. Abstract #44-OR. MBX-102: A Novel Non-TZD Insulin Sensitizer thatImproves Glycemic Control without Causing Edema or Weight Gain in Patientswith Type 2 Diabetes (T2DM) on Concomitant Insulin Therapy. Julio Rosenstock,MD, -Lozano, MD, Sherwyn Schwartz, MD, Guillermo -Galvez, MD and 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 atthe American Diabetes Associations' 65th Scientific Sessions in San Diego.

SOURCE Metabolex, Inc.Web Site: http://www.metabolex.com

VergelProgram for Wellness Restorationpowerusa.orgnelsonvergel.comPlease email me at nelsonvergel@... if you have problems with this email address. ThanksLecture Dates:Chicago June 29,Houston- June 11, Colorado Rocky Mountains- June 17, Miami-Ft Lauderdale- July 18 & 19 (Spanish), Atlanta July 21, Phily Aug 24 /Sept 14, Long Beach Aug 31, NY Sept 8, LA Sept 21, Salt Lake- Nov 5, AIDS Nutritionist Conf- DC Sept 15-17,Houston- US Conf on AIDS- Sept 19-Oct 1, POZ Cruise- Miami- Oct 15-21

DisclaimerThis information (and any accompanying printed material) is not intended to replace the attention or advice of a physician or other health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a qualified health care professional.