In Reply: Telotristat Ethyl for Patients With Carcinoid Syndrome Associated With Chest Pain and Hypertension.

To the Editor:

In the January 2018 issue, Dr Kasi recently reported prescribing telotristat ethyl to 3 patients with carcinoid syndrome and observing grade 3 chest pain and hypertension in all of them, each case within 1 month of initiating treatment.[1] Here we review the clinical trial experience and postmarketing surveillance for these adverse events.

The safety and efficacy of telotristat ethyl were established during phase 3, randomized, placebo-controlled, double-blind clinical trials enrolling subjects with carcinoid syndrome not adequately controlled by current somatostatin analog therapy.[2-4]

During the TELESTAR study, subjects received double-blind placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times daily for 12 weeks (N = 135).[2] Subsequently, they entered a 36-week open-label extension phase during which subjects received telotristat ethyl 500 mg 3 times daily (N = 115).[3] During the TELECAST study, subjects received double-blind placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times daily for 12 weeks (N = 76).[4]

In the integrated safety analysis data from the TELESTAR and TELECAST studies, the incidences of chest pain during the 12-week double-blind treatment period among subjects treated with placebo and telotristat ethyl were 0 and 0.7% (n = 1), respectively. The incidences of hypertension among subjects treated with placebo and telotristat ethyl were 1.4% (n = 1) and 2.9% (n = 4), respectively. In addition, 1 placebo patient and no patient on telotristat ethyl experienced increased blood pressure. At the end of the double-blind treatment period, the mean change from baseline in systolic blood pressure among all subjects who initiated telotristat ethyl was +1 mm Hg. Similarly, the mean change in diastolic blood pressure was +1 mm Hg. There were no serious adverse events related to chest pain or hypertension in these phase 3 studies.[5]

Among subjects with preexisting carcinoid heart disease treated with telotristat ethyl, there was no difference between the adverse event profile of this subgroup and the overall study populations.[4,6]

During the postmarketing experience with telotristat ethyl through December 1, 2017, Lexicon Pharmaceuticals has received a small number of reports for chest pain and hypertension, which is consistent with the clinical trial experience.[7] Postmarketing safety surveillance efforts are ongoing.