Telotristat Etiprate Lessens Carcinoid Syndrome Diarrhea in Phase 3 Trial

A phase 3 trial has demonstrated that treatment with telotristat etiprate can effectively lower the average number of daily bowel movements for individuals with carcinoid syndrome, according to a statement from the developer of the drug, Lexicon.

Carcinoid syndrome occurs as a result of serotonin and other chemicals secreted into the bloodstream by a carcinoid tumor, which is a rare type of cancer that commonly develops in the gastrointestinal (GI) tract or lungs. Telotristat etiprate helps reduce the production of serotonin, thus reducing the severity of carcinoid syndrome-related symptoms, by inhibiting the enzyme tryptophan hydroxylase.

The most common signs and symptoms of carcinoid syndrome include skin flushing, facial skin lesions, diarrhea, difficulty breathing, and a rapid heartbeat. Currently, telotristat etiprate is being tested in individuals for whom these symptoms were not adequately controlled by somatostatin analogs, which are the standard of care for patients with carcinoid syndrome. Based on the promise of the results, Lexicon is working with the FDA for a regulatory submission, according to the statement.

“Carcinoid syndrome is severely debilitating, preventing many patients from leading active and predictable lives, and unfortunately, a majority of patients will not be adequately controlled over time with the current standard of care," Lonnel Coats, president and chief executive officer at Lexicon, said in a statement. "We are committed to working closely with the FDA to file our first new drug application and to bring this innovative new treatment to patients whose lives are already impacted by the challenges of cancer.”

In the phase 3 study, which was known as TELESTAR, all patients continued treatment with a somatostatin analog in combination with either telotristat etiprate or placebo. Two doses of telotristat etiprate were used in the trial, both of which were found to be superior to placebo.

In those receiving a 250 mg dose of telotristat etiprate, there was a 29 percent reduction in the average number of daily bowel movements at week 12 compared with baseline. In a 500 mg arm, there was a 35 percent reduction. Those in the placebo arm experienced a 17 percent reduction in average daily bowel movements.

A greater than 30 percent reduction in daily bowel movements was experienced by 20 percent of patients in the placebo arm compared with 44 percent and 42 percent of those treated with telotristat etiprate in the 250 and 500 mg arms, respectively (P <.04).

In the study, patients experienced similar AEs in the placebo and investigational arms. Those receiving the 250 mg dose experienced GI discomfort and mood-related AEs that were similar to placebo. GI and mood-related AEs were better in the 250 mg arm compared with the 500 mg dose, according to Lexicon. Treatment discontinuations due to serious AEs were similar across all arms.

Other findings from the study are being prepared for presentation at an upcoming medical meeting, according to Lexicon.

"The TELESTAR results are promising, and the community of patients and caregivers who live and deal with carcinoid syndrome are excited about the prospect of a new treatment becoming available," principal investigator of the study Matthew H. Kulke, director, Program in Neuroendocrine and Carcinoid Tumors and Senior Physician, Dana-Farber Cancer Institute, said in a statement.

Telotristat etiprate was granted a fast track designation in 2008 and a subsequent orphan drug designation in 2012. The TELESTAR trial is the first successful phase III trial completed by Lexicon. If approved, telotristat etiprate would be the first therapy approved for carcinoid syndrome in more than 16 years.

A second phase III study, TELEPATH, is exploring expanded treatment with telotristat etiprate at the 250 mg and 500 mg thrice daily for patients with carcinoid syndrome. Treatment-related AEs are the primary endpoint of this study (NCT02026063).