The Woodlands, Texas, – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced top-line results from a pilot study exploring the use of telotristat etiprate in ulcerative colitis. Telotristat etiprate, a serotonin synthesis inhibitor, is currently in Phase 3 development for carcinoid syndrome, a condition caused by metastatic, functioning neuroendocrine tumors. Elevated serotonin is a hallmark of carcinoid syndrome, and two previous Phase 2 clinical trials have shown that clinical benefits of telotristat etiprate treatment were associated with significant reductions in 5-HIAA, a biomarker of serotonin production. Genetic and pharmacological studies in preclinical models had also suggested that reducing serotonin levels might benefit patients with other forms of gastrointestinal disease such as ulcerative colitis.
In this pilot study of mild to moderate ulcerative colitis, telotristat etiprate achieved the primary objective of demonstrating safety and tolerability. Adverse events and discontinuations were evenly distributed between treatment and placebo and there were no serious adverse events attributed to the investigational drug. In addition, telotristat etiprate showed dose-dependent, statistically significant reductions in 5-HIAA from baseline compared to placebo (p < 0.001), with a relationship between the biomarker and certain measures of clinical benefit being observed in the high dose group. Although these results provide a clear signal of activity of the mechanism of action of telotristat etiprate in this patient population, they were not accompanied by other findings that would indicate a large impact on disease modification.
“The top-line results clearly support a favorable safety profile of telotristat etiprate and, importantly, will contribute to our overall safety database for this investigational, orphan drug,” said Pablo Lapuerta, M.D., Lexicon’s chief medical officer. “The reductions in serotonin biosynthesis in this study are consistent with beneficial gastrointestinal effects we have observed in other settings; however, the results from this limited trial do not provide compelling evidence of an effect on the underlying pathogenesis of ulcerative colitis, a standard we require to move forward in this indication. We plan, therefore, to maintain the focus of Lexicon resources on the ongoing Phase 3 program in carcinoid syndrome as the primary indication for telotristat etiprate.”
In this multicenter study, 59 patients with mild-moderate ulcerative colitis were randomized to placebo, a 500 mg dose of investigational drug telotristat etiprate taken orally once daily, or a 500 mg dose of telotristat etiprate three times daily. Treatment was given for 8 weeks. In the context of a pilot study, additional analyses will be conducted to best understand the clinical significance of the results, which are planned for presentation at a scientific congress in 2014.
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has multiple programs in clinical development for diabetes, irritable bowel syndrome, carcinoid syndrome and other indications, 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, characterizations of the results of and projected timing of clinical trials of telotristat etiprate, and the potential therapeutic and commercial potential of telotristat etiprate. The 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. 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, 2012, 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.