Phase 2 Trial of Lexicon's LX1032, Telotristat Etiprate, Shows Positive Results in Carcinoid Syndrome

THE WOODLANDS, Texas, Aug. 9, 2011 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced positive, top-line proof-of-concept data from its recently completed Phase 2 study in carcinoid syndrome with LX1032, telotristat etiprate. Carcinoid syndrome is a chronic condition caused by neuroendocrine tumors that usually originate from the gastrointestinal tract. It is characterized by severe diarrhea and flushing episodes with long-term consequences including malnutrition, heart disease, and death. Symptoms of carcinoid syndrome have been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is designed to reduce serotonin production.

"Telotristat etiprate is our third drug candidate to demonstrate proof of concept in patients in Phase 2," said Dr. Arthur T. Sands, Lexicon's president and CEO. "Based on the positive results of this U.S. study, as well as encouraging observations from our clinical trial in Europe, we intend to discuss a Phase 3 development plan for carcinoid syndrome with the FDA."

The randomized, double-blind, placebo-controlled study was conducted in the United States in 23 patients with carcinoid syndrome who were refractory to currently available therapy. Patients in the study had metastatic carcinoid disease and were experiencing an average of about six bowel movements per day at baseline. Patients received either placebo (n=5) or one of four doses of telotristat etiprate (n=18) daily for 28 days. The primary endpoint of the study was safety and tolerability. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis.

Telotristat etiprate was well tolerated, and adverse events in the study were usually mild to moderate with similar frequencies overall between treatment groups and placebo. Five telotristat etiprate patients achieved clinical responses characterized by reductions of at least 30% in the number of bowel movements per day for two weeks or more during the study. Six telotristat etiprate patients reported adequate relief of carcinoid symptoms at the end of the study. There were nine telotristat etiprate patients with a complete biochemical response defined as a reduction of at least 50% in urinary 5-HIAA, a biomarker of serotonin synthesis. No patients on placebo experienced a clinical response, adequate relief of symptoms, or biochemical response during the study. The difference between telotristat etiprate and placebo in bowel movement frequency ranged between 1.6 and 2.9 bowel movements/day across telotristat etiprate doses, all favoring telotristat etiprate treatment. Also of note, all eligible patients elected to continue treatment with telotristat etiprate under an extension protocol.

Preliminary data were also reported from a separate, ongoing, open-label, single-arm study of telotristat etiprate in Europe. To date, 5 out of 6 patients with refractory carcinoid syndrome have experienced sustained reductions of at least 30% in bowel movement frequency when treated with telotristat etiprate. Two of these responses were within the first 4 weeks of therapy, while three more occurred between 4 and 8 weeks of treatment under the 12-week protocol.

"The Phase 2 data clearly show a reduction in bowel movements and symptom relief in a population that has exhausted all standard-of-care treatment options," said Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon. "The Phase 2 data are also consistent with preliminary results from the European study, where there appear to be some early responses and additional benefit with continued treatment. We look forward to presenting detailed results at a scientific meeting later this year."

Lexicon Conference Call and Webcast:

Lexicon management will be discussing the results of this study in conjunction with the second quarter earnings conference call today at 1:00 p.m. Eastern Time.  The dial-in number for the conference call is 888-220-1244 (within the US/Canada) or 706-679-5615 (international).  The conference ID for all callers is 89449241.  A live webcast of the call can be accessed at www.lexpharma.com.  An archived version of the webcast will be available on Lexicon's corporate website through September 6, 2011.

About Telotristat Etiprate (LX1032)

Telotristat etiprate was discovered and developed at Lexicon to reduce serotonin production by inhibiting tryptophan hydroxylase (TPH), a key enzyme in the synthesis of serotonin.  Excessive levels of serotonin have been implicated in symptoms associated with carcinoid syndrome, especially diarrhea and carcinoid heart disease.  Serotonin's breakdown product, 5-HIAA, is a biomarker used in the diagnosis of the condition.  In preclinical studies, telotristat etiprate reduced peripheral serotonin in several different species without affecting serotonin levels in the brain.  In Phase 1 clinical studies, telotristat etiprate reduced serotonin levels and urinary 5-HIAA in healthy volunteers consistent with preclinical results.  Telotristat etiprate is being developed under Fast Track designation from the U.S. Food and Drug Administration and orphan drug designation from the European Medicines Agency. Telotristat etiprate is a member of a new class of oral drugs invented by Lexicon, the serotonin synthesis inhibitors, which are being developed in a spectrum of gastrointestinal indications.  Lexicon is also currently planning a Phase 2 trial of telotristat etiprate in mild to moderate ulcerative colitis.

About Carcinoid Syndrome

Carcinoid syndrome is a chronic condition caused by metastatic neuroendocrine tumors that usually originate from the gastrointestinal tract.  These tumors secrete large amounts of serotonin, which can cause a variety of symptoms including severe diarrhea and abdominal discomfort.  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 most patients, hence the need for new agents.    

About Lexicon

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 broad 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 LX1032 (telotristat etiprate), including characterizations of the results of and projected timing of clinical trials, 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.  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.