THE WOODLANDS, Texas
Oct. 9, 2013
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
, 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.