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Carcinoid Syndrome Treatment Telotristat Meets Primary Objective in Phase III Trial

If approved, drug would be first oral therapy for this indication

A pivotal phase III study of telotristat etiprate (Lexicon Pharmaceuticals) has met its primary endpoint, demonstrating a clinical benefit in cancer patients with carcinoid syndrome that is not adequately controlled by the current standard of care. If approved, the drug would be the first oral treatment successfully developed for carcinoid syndrome and the first addition to the standard of care in more than 16 years.

Top-line results from the TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial showed that patients who added telotristat etiprate to the standard of care at both the 250-mg and 500-mg doses experienced a statistically significant reduction from baseline compared with placebo in the average number of daily bowel movements over the 12-week study period (P < 0.001), meeting the study’s primary endpoint.

Telotristat etiprate received “fast track” and “orphan drug” designations from the FDA in 2008 and 2012, respectively.

Carcinoid syndrome is a rare disease affecting thousands of patients with neuroendocrine tumors that originate in the gastrointestinal tract and metastasize or spread to the liver or other organs. Overproduction of serotonin within these metastatic neuroendocrine tumor (mNET) cells drives carcinoid syndrome, which is characterized by debilitating diarrhea, facial flushing, abdominal pain, heart valve damage, and other serious consequences.

Telotristat etiprate is the first investigational drug in clinical studies to target tryptophan hydroxylase (TPH), an enzyme that triggers the excess serotonin production within mNET cells that leads to carcinoid syndrome. While current treatments for carcinoid syndrome work to reduce the release of serotonin outside tumor cells, telotristat reduces serotonin production within the cells.

The double-blind TELESTAR trial enrolled 135 patients with carcinoid syndrome that was not adequately controlled by somatostatin analog (SSA) depot injection therapy, the current standard of care. The three-arm study compared two doses of oral telotristat (250 mg and 500 mg), each taken three times daily, with placebo over a 12-week period and measured the reduction from baseline in the average number of daily bowel movements. Patients in both the treatment and placebo arms continued their SSA therapy throughout the study.

Top-line results showed that patients who added telotristat to the standard of care at both the 250-mg and 500-mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (P < 0.001), meeting the study’s primary endpoint.

In addition, in a key secondary measure telotristat achieved a significantly greater durable response rates (44% and 42% in the 250-mg and 500-mg arms, respectively), defined as at least a 30% reduction in daily bowel movements over at least half the days of the study period, compared with a 20% response with placebo (P < 0.040).

Patients who received 250 mg of telotristat experienced a 29% reduction in the average number of daily bowel movements during the final week of the study (week 12) compared with baseline, and those in the 500-mg arm experienced a 35% reduction, whereas the placebo group showed a 17% reduction.

The 12-week study period is being followed by a 36-week open-label extension in which all patients have received telotristat etiprate 500 mg three times daily.

Source: Lexicon Pharmaceuticals; August 3, 2015.

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