Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, presented results from its positive Phase 2 clinical study with LX1031 in patients with non-constipating irritable bowel syndrome (IBS) at Digestive Disease Week (DDW) 2010 in New Orleans, Louisiana.
LX1031 is an oral, serotonin synthesis inhibitor that acts locally in the gastrointestinal tract targeting tryptophan hydroxylase (TPH), an enzyme necessary for the production of serotonin. LX1031 is the first TPH inhibitor to be evaluated in human clinical trials for the treatment of IBS. Results from the randomized, placebo-controlled study of 155 patients with non-constipating IBS showed that patients who received LX1031 (1,000 mg four times a day) for 28 days experienced significant improvement (p<0.05) in global assessment of relief of IBS pain and discomfort over the four-week dosing period as compared to placebo. Corresponding to the improvements in global assessment, significant improvements also occurred in stool consistency. It was noted that an increased clinical response correlated with a reduction in serotonin synthesis as reflected by measures of urinary 5-HIAA. LX1031 was well tolerated, with no notable differences in adverse events observed between placebo and either treatment group.
To validate the mechanism of action of LX1031, treated patients were categorized based on whether or not they reached a threshold of 15% reduction in urinary 5-HIAA, a biomarker of serotonin synthesis. The resulting analysis showed that the 5-HIAA biomarker could distinguish patients who responded to the investigational drug LX1031 across multiple clinically-relevant measures. After four weeks of receiving 1,000 mg of LX1031 four times daily, 73% of patients who reached the biomarker reduction threshold reported experiencing adequate relief of their IBS pain and discomfort as compared to only 11% of patients not meeting the biomarker response threshold (p<0.01). These results illustrate the potential utility of an objective biochemical marker in the management of patients with IBS. In addition, the data suggest the ability to identify patients who are most likely to benefit from therapy with LX1031.
"These findings are especially important in IBS, which has been lacking an objective biochemical marker. The 5-HIAA biomarker correlation with clinical response in this study validates the mechanism of action of LX1031," said Dr. Philip Brown, senior vice president of clinical development at Lexicon. "We intend to integrate measures of 5-HIAA in future clinical development of LX1031, which could reduce variability and improve response rates."
Metabolic markers tied to increased risk of depression and anxiety, study finds