"In this trial, telotristat etiprate provided rapid and durable benefit across several dimensions of carcinoid syndrome, a devastating metastatic cancer syndrome with few treatment options for patients," said Dr. Pablo Lapuerta, Lexicon's senior vice president and chief medical officer. "Of additional interest was improvement seen in two patients who were not on background somatostatin analog therapy, the only currently-approved treatment."
The open-label, dose-escalation study was conducted in Europe in 15 patients with metastatic carcinoid syndrome who were refractory to or could not tolerate somatostatin analog therapy. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis. Patients received ascending doses of 150 mg, 250 mg, 350 mg and 500 mg of telotristat etiprate, administered three times daily (TID), for 14 days on each dose until reaching a maximal dose, which was then continued until the completion of 12 weeks of therapy. Escalation to a higher dose was contingent on tolerability and clinical response. Fourteen patients (93%) completed the trial, and 12 of these 14 patients were treated with 500 mg TID of study drug during the last four weeks of the treatment period. The one patient who discontinued early withdrew from the 350mg TID dose level for reasons not related to drug safety. Notably, the two patients in the study who were not receiving background somatostatin analog therapy observed reductions in bowel movements of 67% and 48% from baseline to week 12.
Telotristat etiprate was well tolerated. There was no evidence of dose–limiting toxicity, and no patient discontinued from the study early due to an adverse event. Only three patients reported a serious adverse event, none of which was related to study drug.
"The positive results from this second Phase 2 trial of telotristat etiprate further support its potential utility in the treatment of carcinoid syndrome in a population that is refractory to or cannot tolerate current therapies," said Dr. Arthur T. Sands, Lexicon's president and chief executive officer. "Building upon results from our previously reported placebo-controlled four-week Phase 2 trial, this study showed strongly positive results in multiple parameters over twelve weeks of therapy, the same treatment period in our upcoming registrational, Phase 3 clinical trial."About Telotristat Etiprate (LX1032) Telotristat etiprate was discovered and developed at Lexicon to reduce serotonin production by inhibiting tryptophan hydroxylase (TPH), a key enzyme in the synthesis of serotonin. Excessive levels of serotonin have been associated with carcinoid syndrome, especially diarrhea and carcinoid heart disease. Serotonin's breakdown product, 5-HIAA, is a biomarker used in the diagnosis of the condition. In preclinical studies, telotristat etiprate reduced 5-HIAA and peripheral serotonin in several different species without affecting serotonin levels in the brain. Telotristat etiprate is being developed under Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration and Orphan Drug designation from the European Medicines Agency. Telotristat etiprate is a member of a new class of oral drugs invented by Lexicon, the serotonin synthesis inhibitors, which are being developed in a spectrum of gastrointestinal indications. Lexicon is also currently carrying out a Phase 2 trial of telotristat etiprate in mild to moderate ulcerative colitis.