Lexicon Pharmaceuticals reports positive results from its LX4211 Phase 2 trial in type 2 diabetic patients

Jan 20 2010

Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, obtained positive results from a recently completed Phase 2 study of LX4211 in patients with type 2 diabetes mellitus.  LX4211 is a once-per-day, orally-delivered, small molecule drug candidate that inhibits the sodium-dependent glucose transporter 2 (SGLT2), lowering the accumulation of glucose in the body and reducing caloric load.  LX4211, dosed as a single agent, provided improvements in glycemic control, demonstrating statistically significant benefits in the primary and multiple secondary efficacy endpoints.

"Results from this important first trial of LX4211 in diabetic patients exceeded our expectations," said Dr. Philip M. Brown, senior vice president of clinical development at Lexicon.  "Rapid improvement in multiple parameters of diabetes, meaningful weight loss, a favorable safety profile and the fact that LX4211-treated patients exhibited improvements in clinically-important metabolic and cardiovascular parameters within four weeks on a single agent is remarkable."

The recently completed study was a four-week, randomized, double-blind, placebo-controlled study in 36 patients with type 2 diabetes.  Patients were randomized to receive either placebo>

There was a marked decrease in fasting plasma glucose throughout the treatment period in both dose groups, with reductions at week four of 53.4 mg/dl and 65.9 mg/dl in the 150 mg and 300 mg dose groups, respectively, as compared to 15.1 mg/dl for placebo.  These decreases in fasting plasma glucose relative to placebo were statistically significant for both LX4211 dose groups>

Importantly, after only four weeks of dosing, average percent hemoglobin A1c (HbA1c), a measure of blood glucose levels over time, was significantly reduced by 1.15 in the 150 mg dose group>

With respect to broader metabolic and cardiovascular safety parameters, patients in both dose groups showed weight reduction accompanied by decreased blood pressure and triglycerides relative to placebo.  LX4211 demonstrated a favorable safety profile in the study with no dose-limiting toxicities.  Adverse events were generally mild and equally distributed across all groups, including the placebo group.

"The magnitude and rapid response in glycemic control, combined with the triglyceride reduction, may distinguish LX4211 from other agents in this class," said Dr. Brian Zambrowicz, chief scientific officer of Lexicon.  "We now believe that the action of LX4211 cannot be entirely explained by glucose excretion in the urine alone, but may also relate to secondary events that both further enhance glycemic control and provide the other metabolic improvements we have witnessed in this study."

In addition to LX4211, Lexicon has three additional drug candidates progressing through Phase 2 clinical trials: LX1032, a peripherally-available serotonin synthesis inhibitor for carcinoid syndrome; LX2931, an S1P lyase inhibitor for rheumatoid arthritis; and LX1031, a locally-acting serotonin synthesis inhibitor for irritable bowel syndrome, which recently completed a Phase 2a clinical trial with positive results.

"We believe the latest encouraging results with LX4211 demonstrate the potential for a therapeutic benefit for patients with type 2 diabetes," said Dr. Arthur T. Sands, president and CEO of Lexicon.  "With positive results within the last few months from Phase 2 clinical trials of two candidates, we are proceeding with confidence that our drug discovery platform has produced investigational new drugs with great promise for patients."