Metabolex announces positive results from phase 2 trial of MBX-8025

Metabolex, Inc. has announced positive results from a Phase 2 clinical trial of MBX-8025.

A summary of the results was presented at the World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy) on November 1, 2008. MBX-8025 is an oral drug candidate that is being evaluated for the treatment of dyslipidemia.

The Phase 2 study was a randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of MBX-8025, both alone and in combination with atorvastatin (marketed as Lipitor(R)), over an 8-week treatment period. The trial enrolled a total of 183 overweight or obese patients with high cholesterol and triglycerides, of whom 173 completed the entire 8 weeks of treatment. The trial was composed of six groups of approximately 30 patients, including two different doses of MBX-8025 (50 mg and 100 mg), both alone and in combination with Lipitor (20 mg), placebo and Lipitor only.

Treatment with MBX-8025 was well tolerated, with no reports of drug-related serious adverse events and no emerging safety findings as compared to placebo and/or Lipitor. Patients treated with MBX-8025 alone experienced an approximate 30% reduction in triglycerides (p < 0.0001) and 20% drop in LDL cholesterol (p < 0.0001) versus placebo after 8 weeks of treatment. In addition, MBX-8025 raised HDL cholesterol by approximately 8% (50 mg; p = 0.068) and 12% (100 mg; p = 0.0045). The triglyceride-lowering effect of MBX-8025 was observed in combination with Lipitor without raising LDL cholesterol.

Additionally, MBX-8025 selectively and substantially depleted the small, dense LDL cholesterol particles, both alone and in combination with Lipitor. These particles convey an independent cardiovascular risk and their depletion represents an added benefit to the LDL lowering itself. Patients treated with MBX-8025 also experienced decreases in fasting insulin and glucose (100 mg; p = 0.01), consistent with improvements in insulin sensitivity. Also observed were significant decreases in GGT and alkaline phosphatase, suggesting a reduction in liver inflammation. MBX-8025 also appeared to have anti-inflammatory effects as indicated by reductions in hsCRP.

"MBX-8025 has the potential to become a next generation treatment for dyslipidemia that simultaneously improves multiple metabolic parameters with a resulting reduction in cardiovascular risk," stated David B. Karpf, MD, Chief Medical Officer of Metabolex. "In this Phase 2 study, MBX-8025 clearly demonstrated robust improvement of many cardiovascular risk factors without any apparent pattern of side effects associated with the drug."

MBX-8025 is a potent, selective PPAR-delta agonist that helps to regulate fatty acid degradation, lipid storage/transport and insulin sensitivity. MBX-8025 is being developed to treat a range of dyslipidemias, and clinical research suggests it has a broad effect on a number of lipid and metabolic parameters, including triglycerides, LDL and HDL cholesterol, insulin sensitivity and inflammation.

Dyslipidemia is characterized by high levels of triglycerides and/or LDL (bad cholesterol) or low levels of HDL (good cholesterol). Dyslipidemia is a key independent risk factor for cardiovascular disease -- the largest therapeutic segment of the world pharmaceutical market. Although some drugs have marked effects on some of the parameters associated with dyslipidemia, existing treatments do not optimally treat all elements of this common condition.