FDA Approves Xermelo for Carcinoid Diarrhea Syndrome

Yesterday, the FDA approved Xermelo (telotristat ethyl) in combination with somatostatin analog (SSA) therapy for the treatment of carcinoid diarrhea syndrome in patients whose symptoms were not adequately controlled by SSA monotherapy, according to a press release.

Carcinoid syndrome is a group of symptoms that are experienced by some patients with carcinoid tumors. These tumors are rare, slow-growing, and occur in the gastrointestinal tract. Carcinoid syndrome affects less than 10% of patients with these tumors, and typically occurs only after liver metastasis.

Patients with carcinoid syndrome release an abnormally high amount of serotonin, which results in uncontrolled diarrhea. Patients can experience weight loss, malnutrition, dehydration, and electrolyte imbalance if diarrhea is not treated, according to the release.

Xermelo was approved in an oral form to be taken 3 times per day, in addition to SSA therapy. The newly approved drug blocks serotonin production by carcinoid tumors, and reduces diarrhea related to carcinoid syndrome.

The safety and efficacy of Xermelo was established in a clinical trial that included 90 patients with well-differentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea, according to the FDA. Patients included in the study experienced 4 to 12 bowel movements per day, regardless of SSA therapy taken for at least 3 months.

In the study, patients remained on SSA therapy, and were randomized to receive placebo or Xermelo 3 times per day. The investigators discovered that patients taking Xermelo had a significant reduction in bowel movement frequency, compared with those treated with placebo.

The researchers noted that 33% of patients treated with Xermelo experienced an average reduction of 2 bowel movements per day, compared with only 4% of patients taking placebo, according to the FDA.

Common adverse events associated with Xermelo included nausea, headache, increased levels of gamma-glutamyl transferase, depression, peripheral edema, flatulence, decreased appetite, and fever. The FDA warns that the drug may result in constipation, and patients who experience less than 4 bowel movements per day may be at an increased risk of constipation.

The FDA advises that patients should be monitored for severe constipation, and if patients develop constipation or abdominal pain, the drug should be discontinued.

Previously, Xermelo was granted fast track designation and priority review to treat this population. The FDA also granted Xermelo orphan drug designation, which provides incentives for the development of drugs that treat rare diseases.

“Today’s approval will provide patients whose carcinoid syndrome diarrhea is not adequately controlled with another treatment option,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.