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Once-daily pill LX4211 controls blood sugar in four weeks, says Lexicon

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Thursday, January 21, 2010, 21:35 This news item was posted in Clinical Trials category and has 0 Comments so far.

LX4211, a once-per-day pill to control diabetes, has shown encouraginf results in a Phase 2 trial, according to Lexicon.

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 patients with type 2 diabetes mellitus.

“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,” stated Dr. Philip M. Brown, senior vice president of clinical development at Lexicon.

Lexicon’s 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 or LX4211, 150 mg or 300 mg , 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.

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 and by 1.25 in the 300 mg dose 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 measured by area under the curve (AUC).

With respect to broader metabolic and cardiovascular safety parameters, patients in both dose groups showed weight reduction accompanied by decreased blood pressure and triglycerides.

LX4211 demonstrated a favorable safety profile in the study with no dose-limiting toxicities.

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).

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. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome.

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.

Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets.

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