Telotristat ethyl

Telotristat ethyl is a prodrug of telotristat that was approved by the FDA in March 2017 as Xermelo. It was previously referred to as telotristat etiprate, the hippurate salt form; however, the FDA recommends the use of the name of the neutral form rather than that of the salt. Currently, telotristat ethyl is used to treat carcinoid syndrome diarrhea from neuroendocrine tumors that are inadequately controlled by short-acting somatostatin analog (SSA) treatment.

Neuroendocrine cells are cells that secrete regulatory peptides and biogenic amines in response to chemical, neural, or other types of stimuli. Neuroendocrine tumors (NET) arising from these cells can therefore secrete chemical mediators into the bloodstream to cause side effects in distant sites, a phenomenon called carcinoid syndrome. The most common peptides and amines secreted by NET are histamines, tachykinins, kallikrein, and serotonin. Overexposure to serotonin can cause severe diarrhea, one of the main clinical symptoms of carcinoid syndrome. Serotonin is metabolized in the urinary metabolite 5-hydroxy indole acetic acid (u5-HIAA), and high levels of u5-HIAA is associated with poor survival outcome in patients with NET. The first line treatment of carcinoid syndrome diarrhea is SSA, but symptoms still reoccur over the course of the disease.