Phase 2 Trial of LX4211 Demonstrates Significant and Rapid Improvements in Multiple Parameters in Type 2 Diabetic Patients
THE WOODLANDS, Texas, Jan. 20 /PRNewswire-FirstCall/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), abiopharmaceutical 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 (n=12) or LX4211, 150 mg (n=12) or 300 mg (n=12), once daily for 28 days. Patients were sequestered, provided a controlled diet and monitored closely throughout the study period.
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 (p=0.001 and p<0.001, respectively). Notably, a substantial percentage (42%) of patients in the 300 mg dose group achieved fasting plasma glucose levels of <105 mg>
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 (p=0.036) and by 1.25 in the 300 mg dose group (p=0.017), as compared to 0.49 in the placebo group. HbA1c levels were reduced to less than or equal to 7% for half the patients in both dose groups; baseline levels were 8.22%, 8.50% and 8.20% for the 150 mg, 300 mg, and placebo groups, respectively. Patients in both dose groups also exhibited significantly improved glucose tolerance in response to oral glucose tolerance testing as compared to patients receiving placebo (p<0.001 for both dose groups), as measured by area under the curve (AUC). Consistent with the mechanism of action of LX4211, there was also a significant, dose-dependent increase in 24-hour urinary glucose excretion throughout the study period relative to placebo in both dose groups (p<0.001 at all time points measured).
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," 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."
About the LX4211 Mechanism of Action
LX4211 was developed at Lexicon as a potent inhibitor of the sodium glucose cotransporter 2 (SGLT2), a transporter responsible for the majority of glucose reabsorption by the kidneys. Lexicon found that mouse knockouts engineered to lack the SGLT2 gene are healthy and require less insulin to manage a glucose challenge. LX4211 may potentially treat diabetes by improving glycemic control as well as providing other metabolic benefits.
Diabetes mellitus is a common metabolic disorder associated with abnormally high blood sugar levels. Diabetes is classified as either type 1, which is characterized by severely diminished insulin production, or type 2, which is characterized by moderately diminished insulin production in conjunction with insulin resistance (insensitivity of the tissues of the body to insulin). Insulin is a hormone that regulates blood glucose levels. Diabetes can seriously impair overall quality of life and may lead to multiple complications including heart disease, stroke, and kidney failure. According to the International Diabetes Federation, more than 245 million people have diabetes, with type 2 diabetes being the most prevalent.
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company's research team. The company has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.
Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to the characterization of the safety and efficacy profile of LX4211 observed in the Phase 2 clinical trial as positive or favorable, the characterization of the results of the Phase 2 clinical trial of LX4211 as demonstrating the potential for a therapeutic benefit for patients with type 2 diabetes, and the potential therapeutic and commercial potential of LX4211 generally. This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX4211 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2008, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
Posted: January 2010