Lexicon Reports Data Of Phase 2 Diabetes Trial

LX4211, dosed as a single agent, provided improvements in glycemic control, demonstrating benefits in the primary and multiple secondary efficacy endpoints.

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, 150mg (n=12) or 300mg (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 53.4mg/dl and 65.9mg/dl in the 150mg and 300mg dose groups, respectively, as compared to 15.1mg/dl for placebo. These decreases in fasting plasma glucose relative to placebo were significant for both LX4211 dose groups (p=0.001 and p<0.001, respectively). Notably, a substantial percentage (42%) of patients in the 300mg dose group achieved fasting plasma glucose levels of <105mg/dl at week four of dosing as compared to placebo (p=0.037).

Importantly, after only four weeks of dosing, average percent hemoglobin A1c (HbA1c), a measure of blood glucose levels over time, was reduced by 1.15 in the 150mg dose group (p=0.036) and by 1.25 in the 300mg 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 150mg, 300mg, and placebo groups, respectively.

Patients in both dose groups also exhibited 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 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.

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.