Press Releases

HAYWARD, CA (March 2, 2004): Metabolex, Inc., today announced the start of its Phase 2 study of its investigational insulin sensitizer, metaglidasen. The double-blind, placebo-controlled study will enroll approximately 200 patients with type 2 diabetes who are currently on insulin, but whose fasting blood-glucose levels are not well controlled. Researchers at 29 centers throughout the United States and Mexico will participate in the study, which is expected to complete in early 2005.

Dr. Schwartz added, “The currently marketed insulin sensitizers, while very effective, are unfortunately associated with a few notable side-effects, such as weight gain, which bothers the patients the most, and edema that can precipitate congestive heart failure, which is of most concern to us physicians. Having a sensitizer that lowers blood glucose and lipids but which causes little-or-no weight gain and edema would be a very substantial advance in our management of the rising diabetes epidemic.”

Dr. Van Wart continued, “Halofenate's sponsor at the time dropped further development of this drug because it exhibited gastrointestinal (GI) side effects. Metabolex scientists discovered that halofenate is an inhibitor of cyclooxygenase-1 (Cox-1), similar to common NSAIDs like Motrin™ or Naprosyn™, accounting for its GI side effects. Metaglidasen is a single enantiomer of halofenate that retains the desirable glucose and lipid-lowering activity of the parent drug, while lacking the Cox-1 inhibition, which was contributed by the other enantiomer. Our Phase 1 study was designed to demonstrate that by removing one of the enantiomers of halofenate, we could eliminate the GI side effects. We used upper GI endoscopy to confirm that metaglidasen does not cause GI toxicity in humans, which was the major hurdle to metaglidasen's successful clinical development.”

Dr. Van Wart noted that over the next 12 -15 months, Metabolex hopes to confirm with metaglidasen the excellent glucose and lipid lowering and lack of edema and weight gain seen in the earlier studies of halofenate. If successful, the company plans to partner metaglidasen for Phase 3 development and commercialization.

Investigators conducted a 10-day, multiple ascending dose study of metaglidasen in 71 patients using doses of up to 1000 mg/day compared to both a placebo-control (24 patients) and a positive-control (Naproxen) (23 patients) group. Trial participants underwent upper GI endoscopies at the 400, 600, 800 and 1000 mg dose levels to study the effects of metaglidasen treatment on the GI mucosa. Results of the study showed good, dose-proportional pharmacokinetics for metaglidasen, and study subjects tolerated the drug well. Moreover, there was no significant GI toxicity observed in metaglidasen-treated individuals or in patients on placebo, while signs of such toxicity were significant in those subjects receiving the positive control drug.

Metabolex, Inc. is a privately held pharmaceutical company dedicated to the discovery and development of drugs to treat diabetes and related metabolic disorders. The company's lead compound, metaglidasen, is a novel insulin sensitizer in Phase 2 clinical development. Metabolex has also built a portfolio of other potential diabetes therapeutics, which includes a product candidate in preclinical development plus several programs optimizing lead drug candidates. Additionally, Metabolex has two target discovery programs that have produced one of the world's largest databases of diabetes-expressed genes. One of these programs, in insulin secretion, is partnered with Pfizer. The other, in insulin resistance, is partnered with Astellas Pharma Inc.