Second Phase 2 Trial Of Telotristat Etiprate Shows Positive Results In Carcinoid Syndrome

THE WOODLANDS, Texas, Oct. 12, 2012 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced positive, top-line data from a recently completed Phase 2 study in carcinoid syndrome with telotristat etiprate. Results from the trial will be presented at the North American Neuroendocrine Tumor Society on Saturday, October 13, 2012 in San Diego, California.

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. Carcinoid syndrome has been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is an oral investigational new drug designed to treat carcinoid syndrome by reducing serotonin production in patients with metastatic carcinoid tumors.  Telotristat etiprate has Fast Track status and Orphan Drug designation from the Food and Drug Administration, and Orphan Drug designation from the European Medicines Agency.

The primary efficacy endpoint of the trial was the reduction of bowel movements from baseline in patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Patients experienced a 46.4% median reduction from baseline at week 12, with the number of daily bowel movements steadily decreasing over time. All observed changes from baseline were statistically significant at p < 0.001. This change corresponded with an increased proportion of patients reporting adequate relief of their carcinoid symptoms, a global assessment which also improved over time, with 75% of the patients with data at week 12 reporting improvement. Clinically relevant decreases from baseline were likewise seen for a number of key secondary endpoints, including statistically significant improvements in stool consistency (p < 0.001) and trends of reductions in abdominal pain (p=0.09) and the number of cutaneous flushing episodes (p=0.052). The median percentage reductions from baseline of urinary 5-HIAA at weeks 8 and 12 were 68.3% (p=0.019) and 72.7% (p=0.031), respectively. Urinary 5-HIAA is a biomarker of serotonin synthesis and is of key interest in these patients.

"In this trial, telotristat etiprate provided rapid and durable benefit across several dimensions of carcinoid syndrome, a devastating metastatic cancer syndrome with few treatment options for patients," said Dr. Pablo Lapuerta, Lexicon's senior vice president and chief medical officer. "Of additional interest was improvement seen in two patients who were not on background somatostatin analog therapy, the only currently-approved treatment."

The open-label, dose-escalation study was conducted in Europe in 15 patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis. Patients received ascending doses of 150 mg, 250 mg, 350 mg and 500 mg of telotristat etiprate, administered three times daily (TID), for 14 days on each dose until reaching a maximal dose, which was then continued until the completion of 12 weeks of therapy. Escalation to a higher dose was contingent on tolerability and clinical response. Fourteen patients (93%) completed the trial, and 12 of these 14 patients were treated with 500 mg TID of study drug during the last four weeks of the treatment period. The one patient who discontinued early withdrew from the 350mg TID dose level for reasons not related to drug safety. Notably, the two patients in the study who were not receiving background somatostatin analog therapy observed reductions in bowel movements of 67% and 48% from baseline to week 12.

Telotristat etiprate was well tolerated. There was no evidence of dose–limiting toxicity, and no patient discontinued from the study early due to an adverse event. Only three patients reported a serious adverse event, none of which was related to study drug.

"The positive results from this second Phase 2 trial of telotristat etiprate further support its potential utility in the treatment of carcinoid syndrome in a population that is refractory to or cannot tolerate current therapies," said Dr. Arthur T. Sands, Lexicon's president and chief executive officer. "Building upon results from our previously reported placebo-controlled four-week Phase 2 trial, this study showed strongly positive results in multiple parameters over twelve weeks of therapy, the same treatment period in our upcoming registrational, Phase 3 clinical trial."

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 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 5-HIAA and peripheral serotonin in several different species without affecting serotonin levels in the brain.  Telotristat etiprate is being developed under Fast Track and Orphan Drug 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 carrying out 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.  Patients with carcinoid syndrome currently have limited therapeutic options, and the standard of care includes chronic therapy with somatostatin analogs, which are delivered by injection.  With current therapy, carcinoid syndrome 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 programs in mid-stage development for diabetes, carcinoid syndrome, irritable bowel 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 telotristat etiprate (LX1032), including characterizations of the results of and projected timing of clinical trials, and the potential therapeutic and commercial potential of telotristat etiprate.  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 telotristat etiprate 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, 2011, 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.