FDA News

FDA approves Xermelo for carcinoid syndrome diarrhea in patients with metastatic neuroendocrine tumors

The FDA approved telotristat ethyl tablets for use in combination with somatostatin analog therapy for the treatment of adults with carcinoid syndrome diarrhea.

The approval is intended for patients with carcinoid syndrome — a rare and debilitating condition that affects people with carcinoid tumors and metastatic neuroendocrine tumors — that somatostatin analog therapy alone inadequately controlled. Carcinoid syndrome occurs in less than 10% of patients with carcinoid tumors. The tumors cause the excess release of the hormone serotonin, resulting in diarrhea, which in turn can lead to weight loss, malnutrition, dehydration and electrolyte imbalance.

Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) — which targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within metastatic neuroendocrine tumor cells — is the first and only approved oral therapy for carcinoid syndrome diarrhea.

“Today’s approval of telotristat ethyl represents a shift in the treatment paradigm of carcinoid syndrome diarrhea for cancer patients who are inadequately controlled by somatostatin analog therapy and, until now, have had limited options to manage this debilitating condition,” Lonnel Coats, president and CEO of Lexicon, said in a company-issued release. “We are proud to have discovered and developed this ground-breaking orphan drug, and it is an honor to make it available for the thousands of patients currently suffering from this condition who wish to lead a more routine life with fewer incidences of severe diarrhea.”

A 12-week, double blind, placebo-controlled trial compared the safety and efficacy of adding telotristat ethyl to somatostatin analog therapy in 90 adults with well-differentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea. Before the trial, patients had four to 12 bowel movements a day despite use of somatostatin analog therapy for 3 months or longer.

Thirty-three percent of patients treated with telotristat ethyl experienced an average reduction of two bowel movements per day compared with 4% of patients treated with somatostatin analog therapy alone.

“Inhibition of tumoral serotonin production represents a novel approach for patients with this condition,” study researcher Matthew H. Kulke, MD, director of the program in neuroendocrine and carcinoid tumors at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said in the press release. “Studies have shown that telotristat ethyl can reduce the debilitating effects of carcinoid syndrome diarrhea and has a favorable efficacy and safety profile in patients who currently have limited treatment options.”

The most common side effects included nausea, headache, increased levels of the liver enzyme gamma-glutamyl transferase, depression, accumulation of fluid causing swelling, flatulence, decreased appetite and fever.

The FDA noted telotristat ethyl may cause constipation, and the risk for developing constipation may be greater in patients with less than four bowel movements per day. Telotristat ethyl is now available by prescription and will be in select specialty pharmacies beginning March 6. The therapy is approved in tablet form to be taken orally three times daily with food.

 

The FDA approved telotristat ethyl tablets for use in combination with somatostatin analog therapy for the treatment of adults with carcinoid syndrome diarrhea.

The approval is intended for patients with carcinoid syndrome — a rare and debilitating condition that affects people with carcinoid tumors and metastatic neuroendocrine tumors — that somatostatin analog therapy alone inadequately controlled. Carcinoid syndrome occurs in less than 10% of patients with carcinoid tumors. The tumors cause the excess release of the hormone serotonin, resulting in diarrhea, which in turn can lead to weight loss, malnutrition, dehydration and electrolyte imbalance.

Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) — which targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within metastatic neuroendocrine tumor cells — is the first and only approved oral therapy for carcinoid syndrome diarrhea.

“Today’s approval of telotristat ethyl represents a shift in the treatment paradigm of carcinoid syndrome diarrhea for cancer patients who are inadequately controlled by somatostatin analog therapy and, until now, have had limited options to manage this debilitating condition,” Lonnel Coats, president and CEO of Lexicon, said in a company-issued release. “We are proud to have discovered and developed this ground-breaking orphan drug, and it is an honor to make it available for the thousands of patients currently suffering from this condition who wish to lead a more routine life with fewer incidences of severe diarrhea.”

A 12-week, double blind, placebo-controlled trial compared the safety and efficacy of adding telotristat ethyl to somatostatin analog therapy in 90 adults with well-differentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea. Before the trial, patients had four to 12 bowel movements a day despite use of somatostatin analog therapy for 3 months or longer.

Thirty-three percent of patients treated with telotristat ethyl experienced an average reduction of two bowel movements per day compared with 4% of patients treated with somatostatin analog therapy alone.

“Inhibition of tumoral serotonin production represents a novel approach for patients with this condition,” study researcher Matthew H. Kulke, MD, director of the program in neuroendocrine and carcinoid tumors at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said in the press release. “Studies have shown that telotristat ethyl can reduce the debilitating effects of carcinoid syndrome diarrhea and has a favorable efficacy and safety profile in patients who currently have limited treatment options.”

The most common side effects included nausea, headache, increased levels of the liver enzyme gamma-glutamyl transferase, depression, accumulation of fluid causing swelling, flatulence, decreased appetite and fever.

The FDA noted telotristat ethyl may cause constipation, and the risk for developing constipation may be greater in patients with less than four bowel movements per day. Telotristat ethyl is now available by prescription and will be in select specialty pharmacies beginning March 6. The therapy is approved in tablet form to be taken orally three times daily with food.