Buoyed by Dana-Farber-led research, FDA approves first oral drug for cancer-related diarrhea syndrome

Spurred by the results of trials led by Dana-Farber Cancer Institute’s Matthew Kulke, MD, the Food and Drug Administration (FDA) has approved Xermelo™, the first oral treatment for carcinoid syndrome diarrhea, a rare but potentially debilitating condition in patients with neuroendocrine tumors.

The approval promises to improve the lives of the approximately 14,000 people in the United States who have been diagnosed with the syndrome and have had few options for managing it. The condition produces frequent, severe diarrhea that can interfere with the ability to lead an active life, as well as cause facial flushing, abdominal pain, fatigue, and, over time, heart valve damage. At risk for the condition are patients with neuroendocrine tumors, cancers of the hormonal and nervous systems that usually occur in the intestine but may also arise in the pancreas, lung, and elsewhere in the body. Not all such tumors are malignant, but even people with benign forms are at risk for the diarrhea syndrome.

Xermelo is a first-in-class drug that targets the overproduction of serotonin, a chemical transmitter of nerve signals, inside neuroendocrine cells. The first clinical study of Xermelo (also called Telotristat Ethyl) was led by Kulke and performed at Dana-Farber. This initial study provided early evidence of both safety and efficacy. The FDA approval is based on safety and efficacy data from the subsequent international phase 3 TELESTAR trial also led by Kulke. The trial demonstrated that patients who took Xermelo in combination with somatostatin analogs (SSAs), agents which slow the production of certain hormones, had significantly fewer bowel movements over a 12-week period than did patients taking a placebo. Forty-four percent of the patients treated with Xermelo had at least a 30 percent reduction in bowel movement frequency for at least half the 12-week study period.

“The FDA approval of Xermelo establishes a new treatment option that works within the tumor cells to inhibit serotonin production, a novel approach and new treatment pathway,” said Kulke, director of Dana-Farber’s Program in Neuroendocrine and Carcinoid Tumors. “Data from TELESTAR demonstrated that Xermelo can reduce the debilitating effects of carcinoid syndrome diarrhea, with a favorable efficacy and safety profile, even for individuals who have experienced limited success with above-label dosing of SSAs.”