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Metabolex Initiates Phase 2/3 Trial of Metaglidasen in Patients With Type 2 Diabetes

Posted on: Saturday, 10 June 2006, 12:00 CDT

HAYWARD, Calif. and WASHINGTON, June 10 /PRNewswire/ -- Metabolex, Inc. announced today the initiation of a Phase 2/3 trial of its lead product candidate, metaglidasen, in patients with type 2 diabetes. A novel insulin sensitizer, metaglidasen has been shown in a previously conducted Phase 2 trial in patients with diabetes to be well tolerated and to lower blood glucose, triglycerides and uric acid levels without causing any increase in weight gain or edema, the common side effects of the currently marketed insulin sensitizers from the thiazolidinedione (TZD) class.

"The initiation of this trial of metaglidasen underscores our commitment to developing this drug to treat patients with type 2 diabetes, for whom limited treatment options are available due to dose-limiting side effects associated with currently available insulin sensitizers," said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. "Previous clinical trial findings suggest that metaglidasen is effective in controlling blood glucose levels, with a promising side effect profile. We believe metaglidasen has the potential to markedly improve the standard of care for patients with type 2 diabetes."

The randomized, double-blind, placebo- and active comparator-controlled, multicenter Phase 2/3 trial is evaluating metaglidasen at daily doses of 200, 400 and 600 mg versus Actos(R) (pioglitazone, a TZD) 30 mg in approximately 400 patients with type 2 diabetes taking concomitant insulin. The primary endpoint is hemoglobin A1c (HbA1c) levels -- the gold-standard measure of a patient's blood glucose control over time. Fasting blood glucose, triglycerides, cholesterol, uric acid and adiponectin levels also will be evaluated. The trial will be conducted at up to 75 clinical sites in the U.S. and other select countries.

Preclinical Findings Suggest Metaglidasen Benefit Extends Beyond Insulin Sensitization

Preclinical findings, to be presented during a poster session at the American Diabetes Association's 66th Annual Scientific Sessions, have demonstrated that metaglidasen helps maintain insulin levels and preserve the function of beta cells, the pancreatic cells that produce insulin. In patients with type 2 diabetes, damage to the beta cells as well as a systemic inability to respond to insulin occurs. Researchers believe that insulin sensitizers may benefit patients by both preventing damage to beta cells and increasing insulin sensitization.

In one study, mice with pre-existing diabetes were treated with metaglidasen, rosiglitazone (a currently marketed TZD) or control vehicle. Those treated with metaglidasen had a three-fold higher pancreatic insulin content and a higher beta cell mass compared with controls, suggesting that metaglidasen had a protective effect on the beta cells. These effects were similar to those observed in mice treated with rosiglitazone, although weight gain was lower in the metaglidasen-treated mice. In a second study of mice treated before symptoms of diabetes appeared, those treated with metaglidasen had a six-fold greater pancreatic insulin content compared with controls.

"These preclinical findings indicate that metaglidasen may have a dual mechanism of action -- not only helping to improve insulin sensitivity in peripheral tissues such as muscle, fat and liver, but also protecting against the destruction of the insulin-producing beta cells," added Dr. Van Wart. "Preventing destruction of beta cells could protect pre-diabetes patients from developing type 2 diabetes and substantially delay the need for insulin therapy in patients who already have type 2 diabetes. Continued clinical studies will help us better characterize metaglidasen's potential range of benefits."

About Metaglidasen

Insulin resistance is a major underlying cause of type 2 diabetes, and insulin sensitizers can both treat and delay the progression of the disease. The currently marketed insulin sensitizers, which are from the TZD chemical class and are full PPAR-gamma agonists, have worldwide sales of nearly $4 billion. They represent an attractive treatment option for type 2 diabetes because they target insulin resistance and may preserve the function of pancreatic beta cells (the source of insulin). However, these drugs exhibit the dose-limiting side effects of 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.

Metaglidasen, a selective PPAR-gamma modulator (SPPARM), has a different chemical structure and method of action from the TZD insulin sensitizers. As a result, it may be able to treat insulin resistance with a side effect profile that is superior to that of the TZDs. Results presented at the American Diabetes Association's 65th Scientific Sessions in June 2005 showed that metaglidasen exhibited clinically significant lowering of blood glucose without causing an increase in weight gain or edema relative to placebo.

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. For additional information about Metabolex and its development pipeline, visit http://www.metabolex.com/.

ADA Abstract #1396-P. Metaglidasen, a Novel Selective Peroxisome Proliferator-Activated Receptor-gamma Modulator, Preserves Pancreatic Islet Structure and Function in db/db Mice. Fang Zhang, Edward Clemens, Francine M. Gregoire, Maria Wilson, Richard W. Gelling, Judith Udove, James Tang and Thomas Gustafson. To be presented on Sunday, June 11, 2006, at noon EDT during the "Integrated Physiology, Insulin Secretion in Vivo" poster session at the American Diabetes Associations' 66th Scientific Sessions in Washington, D.C.

Metabolex, Inc.

CONTACT: Mark Bagnall of Metabolex, +1-510-293-8800, ormbagnall@metabolex.com; or Media, Daryl Messinger of WeissComm Partners,+1-415-999-2361, or daryl@weisscommpartners.com, for Metabolex

Web site: http://www.metabolex.com/

Source: PRNewswire

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