* Drug Candidate Will Advance to Phase 2 Clinical Trial in Carcinoid Patients * Potent Reduction in Serotonin Achieved * Drug Candidate Being Developed Under Fast Track Status From FDA
THE WOODLANDS, Texas, Nov. 13, 2008 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced today that it has successfully completed a second Phase 1 clinical trial of LX1032, an orally-delivered small molecule drug candidate for managing gastrointestinal symptoms associated with carcinoid syndrome. Based on the results from this study, Lexicon is planning to initiate a Phase 2 study in patients with carcinoid syndrome. LX1032 will be Lexicon's third drug candidate to progress to Phase 2 clinical trials.
In the recently-completed Phase 1b multiple ascending-dose trial, LX1032 was well tolerated at all doses, including the maximum daily dose of 1,500 mg over the 14-day dosing period. Results from this trial demonstrated a potent reduction in both blood serotonin levels and urinary 5-HIAA, a marker of serotonin biosynthesis, at doses from 500 mg to the maximum dose of 1,500 mg, indicating that the target of LX1032 represents a new mechanism for regulating peripheral serotonin synthesis. The reduction in blood serotonin and urinary 5-HIAA levels observed in the multiple-dose study in normal healthy volunteers is consistent with the reduction in serotonin levels observed in preclinical animal models -- demonstrating conservation of the mechanism of action from mouse to man.
"The substantial reduction in serotonin observed in this study confirms our preclinical observations and suggests potent inhibition of peripheral serotonin production," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "We are eager to test the compound in patients with carcinoid syndrome who suffer from significant gastrointestinal symptoms relating to the overproduction of serotonin."
In June 2008, Lexicon received Fast Track designation from the FDA for development of LX1032. Fast Track status facilitates the development of potential new drugs and expedites the review of new drugs intended to serve unmet medical needs in serious or life-threatening conditions.
Clinical development of LX1032 is being funded through a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.
Video Presentation on LX1032
For additional information about the results of this study, please view the video presentation on Lexicon's website, www.lexpharma.com.
About the Clinical Trial
The Phase 1b trial was a randomized, double-blind, placebo-controlled, multiple ascending-dose study assessing the safety, tolerability, and pharmacokinetics of LX1032 in 40 healthy volunteers. Five dose levels of LX1032, ranging from 100 mg to 1,500 mg daily, were assessed. LX1032 was well tolerated at all dose levels and produced a dose-dependent reduction in blood serotonin and urinary 5-HIAA levels, with maximal, statistically-significant reductions observed at doses at or above 500 mg. A dose-dependent, mild increase in hepatic transaminase levels was observed, a finding that will be monitored in future trials. No serious adverse events were reported. In a prior Phase 1a clinical trial, a dose-dependent decrease in urinary 5-HIAA levels was observed with single doses of LX1032.
About the Target
The target for LX1032 was identified through the Genome5000(tm) program, Lexicon's initiative to identify the functions of 5,000 druggable genes in the human genome. LX1032 was discovered and developed at Lexicon as a potent inhibitor of tryptophan hydroxylase (TPH), a rate-limiting enzyme in the synthesis of serotonin. Excessive levels of serotonin have been implicated in symptoms associated with carcinoid syndrome. Serotonin's breakdown product, 5-HIAA, is a biomarker used in the diagnosis of the condition. In preclinical studies, LX1032 was able to reduce peripheral serotonin and urinary 5-HIAA levels in several different species without affecting serotonin levels in the brain.
About the Disease
Carcinoid syndrome is a chronic condition that is the result of metastatic neuroendocrine tumors that usually originate from enterochromaffin cells in the gastrointestinal tract. These tumors secrete large amounts of serotonin, which can cause a variety of symptoms including severe diarrhea and abdominal discomfort. According to the American Cancer Society, about 11,000 to 12,000 neuroendocrine tumors and neuroendocrine cancers are diagnosed each year in the United States. Patients with carcinoid syndrome currently have limited therapeutic options, and the standard of care includes chronic therapy with somatostatin analogues, which are delivered by injection. With current therapy, the gastrointestinal symptoms return over time in the vast majority of patients, hence the need for new agents. Lexicon was granted Fast Track designation from the FDA to specifically develop LX1032 for the treatment of gastrointestinal symptoms associated with carcinoid syndrome in patients who no longer respond to the standard of care.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has six drug candidates in development for autoimmune disease, carcinoid syndrome, cognitive disorders, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company's research team. Lexicon's goal is to advance 10 drug candidates into human clinical trials by the end of 2010, the strategic objective of its 10TO10 program. The company's pipeline derives from its use of its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has applied small molecule chemistry and antibody technology to 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.
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Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX1032 and the potential therapeutic and commercial potential of LX1032. 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 LX1032 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. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2007, 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.