New Mechanisms of Action

Telotristat etiprate (LX1032/LX1606)

Carcinoid Syndrome


Telotristat etiprate is an orally-delivered small molecule that acts by inhibiting the enzyme tryptophan hydroxylase (TPH), the rate-limiting enzyme responsible for serotonin production. Telotristat etiprate was specifically designed to be absorbed into the blood stream without crossing the blood brain barrier so as not affect brain serotonin levels. In carcinoid syndrome, serotonin is known to be secreted from metastatic carcinoid tumors which most commonly arise from the gastrointestinal tract. Excess serotonin production by tumor cells has been associated with severe diarrhea, gastrointestinal pain and discomfort, and heart valve damage.

Telotristat etiprate reduces peripheral serotonin production by inhibiting the enzyme TPH in metastatic carcinoid tumors.

Clinical Data

Results from a placebo-controlled, Phase 2 study in the United States in 23 patients with metastatic carcinoid syndrome who were refractory to currently available therapy indicated that telotristat etiprate was well tolerated and demonstrated positive response in key measures of efficacy, including reduction in bowel movements, reduction of serotonin production, and increased rates of patient-reported adequate relief of carcinoid symptoms.

In a second, open-label Phase 2 trial in Europe, telotristat etiprate also showed evidence of clinical benefit across several endpoints in carcinoid syndrome patients. Benefits included reductions in bowel movement frequency, decreased urinary 5-HIAA (a biomarker of serotonin synthesis), and improvements in patient-reported relief of symptoms.

For more detailed information regarding the top-line Phase 2 results, please see our press releases for the first and second trial.

Telotristat etiprate is currently being evaluated in a multi-national Phase 3 development program for carcinoid syndrome.

About Fast Track Designation
Telotristat etiprate has received Fast Track designation from the United States Food and Drug Administration (FDA) for the treatment of symptoms associated with carcinoid syndrome in certain patients.  FDA’s Fast Track program 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.  Fast Track status also provides formal mechanisms for sponsors to communicate with the FDA on product development issues, including clinical trial design.  Fast Track benefits include eligibility for an early review process that may significantly shorten FDA approval times by allowing for the possibility of a “rolling submission” for marketing authorization.

About Orphan Designation
Telotristat etiprate has received orphan drug designation from both the FDA and the European Medicines Agency (EMA). The goal of the FDA and EMA orphan drug programs are to promote the development of drugs intended for the prevention or treatment of life-threatening or chronically debilitating conditions that affect limited populations.  Incentives for developing new drugs under orphan drug designation in the U.S. and E.U. include 7 and 10 years of marketing exclusivity, respectively, regulatory assistance, reduced regulatory fees associated with applying for marketing approval and assistance with clinical trial design.

About Carcinoid Syndrome
Carcinoid tumors are a type of neuroendocrine tumor (NET) that typically form in the gastrointestinal system.  Carcinoid NETs may arise from multiple different organ systems, including the small bowel, appendix, rectum, stomach, and lung, but most are derived from enterochromaffin (EC) cells of the midgut, and often produce and release large amounts of serotonin (5-HT).  Carcinoid syndrome is a combination of symptoms, including severe diarrhea, bronchial restriction, facial flushing and rapid heartbeat, caused by the release of excessive serotonin and other substances into the blood stream from metastatic carcinoid tumors.

Carcinoid syndrome is a combination of symptoms caused
by the release of excessive serotonin and other substances
into the blood stream from metastatic carcinoid tumors.

Carcinoid Syndrome Prevalence

According to the American Cancer Society there are approximately 100,000 patients with carcinoid tumors in the U.S.  About 10% of people with carcinoid tumors will develop carcinoid syndrome and many of these patients will often live for several years without adequate relief of their symptoms.

Related Publications
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* Safety and efficacy have not been evaluated by any regulatory authorities for the indications described.