Washington: The US Food and Drug Administration on Tuesday approved Xermelo (telotristat ethyl) tablets in combination with somatostatin analogue (SSA) therapy for the treatment of adults with carcinoid syndrome diarrhoea that SSA therapy alone has inadequately controlled.
Carcinoid syndrome is a cluster of symptoms sometimes seen in people with carcinoid tumours. These tumours are rare, and often slow-growing. Most carcinoid tumours are found in the gastrointestinal tract. Carcinoid syndrome occurs in less than 10 percent of patients with carcinoid tumours, usually after the tumour has spread to the liver. The tumours in these patients release excess amounts of the hormone serotonin, resulting in diarrhoea. Complications of uncontrolled diarrhoea include weight loss, malnutrition, dehydration, and electrolyte imbalance.
“Today’s approval will provide patients whose carcinoid syndrome diarrhoea is not adequately controlled with another treatment option,” said Dr Julie Beitz, director of the Office of Drug Evaluation III in the FDA’s Centre for Drug Evaluation and Research.
Xermelo, in a regimen with SSA therapy, is approved in tablet form to be taken orally three times daily with food. Xermelo inhibits the production of serotonin by carcinoid tumours and reduces the frequency of carcinoid syndrome diarrhoea.
The safety and efficacy of Xermelo were established in a 12-week, double-blind, placebo-controlled trial in 90 adult participants with well-differentiated metastatic neuroendocrine tumours and carcinoid syndrome diarrhoea. These patients were having between four to 12 daily bowel movements despite the use of SSA at a stable dose for at least three months. Participants remained on their SSA treatment, and were randomized to add placebo or treatment with Xermelo three times daily. Those receiving Xermelo added on to their SSA treatment experienced a greater reduction in average bowel movement frequency than those on SSA and placebo. Specifically, 33 percent of participants randomized to add Xermelo on to SSA experienced an average reduction of two bowel movements per day compared to 4 percent of patients randomized to add placebo on to SSA.
The most common side effects of Xermelo include nausea, headache, increased levels of the liver enzyme gamma-glutamyl transferase, depression, accumulation of fluid causing swelling (peripheral oedema), flatulence, decreased appetite and fever. Xermelo may cause constipation, and the risk of developing constipation may be increased in patients whose bowel movement frequency is less than four bowel movements per day. Patients treated with a higher than recommended dosage of Xermelo developed severe constipation in clinical trials. One patient required hospitalization and two other patients developed complications of either intestinal perforation or intestinal obstruction.
According to the FDA, patients should be monitored for severe constipation. If a patient experiences severe constipation or severe, persistent or worsening abdominal pain, they should discontinue Xermelo and contact their healthcare provider.
The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
Xermelo is manufactured by Woodlands, Texas-based Lexicon Pharmaceuticals, Inc.
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