- Favorable Safety Profile Demonstrated in Study
THE WOODLANDS, Texas, July 28, 2011 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced today that it has successfully completed a Phase 1 clinical trial of LX1033, an orally-delivered small molecule drug candidate for diarrhea-predominant irritable bowel syndrome (IBS-d). Lexicon plans to move LX1033 forward into a Phase 2 study in patients with IBS-d.
Top-line results demonstrated that LX1033 was well tolerated at all doses and produced a statistically significant reduction in serotonin synthesis compared to placebo, as measured by both plasma (p<0.001) and urinary (p<0.01) 5-hydroxyindoleacetic acid (5-HIAA), a biomarker for serotonin synthesis. Importantly, a greater reduction in serotonin synthesis was achieved with lower and less frequent dosing and at lower drug exposure levels than was observed with Lexicon's first generation serotonin synthesis inhibitor, LX1031, which had previously demonstrated clinical benefit to IBS patients in a Phase 2a clinical trial as measured by both global assessment of adequate relief and stool consistency.
"Based on the completed LX1033 Phase 1 program, we are confident that a convenient dose regimen of this compound can provide the level of serotonin reduction that we have previously associated with clinical benefit for patients with IBS-d," said Dr. Brian Zambrowicz, chief scientific officer at Lexicon. "We were also impressed by the performance of the blood test for measuring 5-HIAA and anticipate using this biomarker to guide future drug development of LX1033."
The LX1033 Phase 1 trial was conducted as a randomized, placebo-controlled trial in healthy volunteers. In the multiple ascending dose portion of the study, doses of 250 mg, 500 mg, and 750 mg given three times daily, as well as 1,000 mg given twice daily, were administered over the course of 14 days. There were eight healthy volunteers (six receiving active compound, two receiving placebo) in each dose group. Study endpoints included safety and tolerability together with pharmacokinetic and pharmacodynamic parameters consisting of measures of both plasma and urinary 5-HIAA. Data from the study showed that LX1033 produced a statistically significant decrease in both plasma and urinary 5-HIAA as compared to placebo at all doses tested. Notably, the plasma measures of 5-HIAA in the recent study were obtained from a simple morning blood draw and correlated with results obtained by the traditional 24-hour urine collection method.
"The favorable safety and tolerability profile for LX1033, together with its local site of action within the gastrointestinal tract and ability to potently reduce serotonin synthesis, make this a very attractive candidate for clinical trials in IBS-d, where the need for new treatments is great," said Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon. "We look forward to advancing this drug into a Phase 2 trial where we can examine safety and efficacy in IBS-d."
LX1033 is an orally-delivered drug candidate for IBS that inhibits tryptophan hydroxylase (TPH), a key enzyme in the synthesis of serotonin. LX1033 is designed to act locally in the gastrointestinal (GI) tract by reducing the serotonin available for receptor activation, without affecting serotonin levels in the brain.
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has four drug candidates in mid-stage development for diabetes, irritable bowel syndrome, carcinoid syndrome and rheumatoid arthritis, all of which were discovered by Lexicon's research team. Lexicon 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. For additional information about Lexicon and its programs, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX1031 and LX1033, including characterizations of the results of and projected timing of clinical trials of such compounds, and the potential therapeutic and commercial potential of LX1031 and LX1033. 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 LX1031 and LX1033 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. Unless specifically indicated otherwise, results reported as trends were not statistically significant. Information identifying such important factors is contained under "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2010, 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.
SOURCE Lexicon Pharmaceuticals, Inc.