Lexicon Pharmaceuticals, Inc announced that the company's investigational new drug, LX1031, a tryptophan hydroxylase (TPH) inhibitor, demonstrated positive results in clinically important parameters for the treatment of non-constipating irritable bowel syndrome (IBS). Top-line results showed that treatment with one gram of LX1031 four times daily produced a statistically significant improvement in global assessment of relief of IBS pain and discomfort over the four-week dosing period as compared to placebo (p=0.0465). Improvements in global assessment parameters also corresponded with statistically significant improvements in stool consistency. Notably, increased clinical response correlated with a greater reduction in serotonin synthesis as reflected by measures of urinary 5-HIAA, a breakdown product of serotonin.

"Treatment with LX1031 reduced symptoms of IBS in this clinical trial, and holds promise for patients with this disease," said Dr Brian Zambrowicz, chief scientific officer at Lexicon. "We believe the fact that the clinical benefit was correlated to the reduction in the 5-HIAA biomarker validates our therapeutic strategy of inhibiting TPH as a novel treatment option for patients with IBS. The overall safety and efficacy profile observed to date supports further development of this novel mechanism in IBS."

The phase-2 clinical trial, which began at the end of December 2008, was a four-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX1031 and its effects on symptoms associated with IBS. The study included 155 patients with either diarrhoea-predominant IBS or mixed IBS. Two dose levels were evaluated: a 250 mg dose and a 1,000 mg dose, each administered four times daily (QID). LX1031 was well tolerated, with no statistically significant differences in adverse events observed between placebo and either treatment group. Efficacy endpoints evaluated included a global assessment of adequate relief, as well as measures of specific symptoms associated with IBS. Based on the positive data obtained, Lexicon intends to pursue the development of LX1031 as a novel treatment for patients with IBS.

"We are pleased with the outcome of this proof-of-concept trial as we continue to advance our pipeline of drug candidates with new mechanisms of action," said Dr Arthur T Sands, president and chief executive officer of Lexicon. "These results further validate our genetic strategy to discover breakthrough treatments for human disease."

Lexicon has three additional drug candidates progressing through phase-2 clinical trials including LX1032, a peripherally-available TPH inhibitor for carcinoid syndrome, LX2931, an S1P lyase inhibitor for rheumatoid arthritis, and LX4211, an SGLT2 inhibitor for type-2 diabetes. Phase-2 clinical results from these programs are expected over the next 12 months.

LX1031 was discovered and developed by Lexicon as an oral drug candidate for IBS following Lexicon's identification of the TPH target as a key control point for the regulation of peripheral serotonin production.

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease.