The recent first global approval of telotristat ethyl has been reviewed in detail in the First Global Approval report in Adis journal Drugs, based on the development milestones tracked in AdisInsight.
In February 2017, Telotristat Ethyl (Xermelo™), developed by Lexicon Pharmaceuticals, received its first global approval in the USA for the treatment of carcinoid syndrome diarrhoea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy.1 Telotristat ethyl is a first-in-class, small-molecule, peripheral oral tryptophan hydroxylase (TPH) inhibitor, formulated as the hippurate salt, telotristat etiprate. It reduces the production of serotonin (5-HT), which can cause many symptoms, including diarrhoea, when secreted by neuroendocrine tumours into the blood stream.
Carcinoid syndrome is a rare and potentially debilitating condition that affects people with metatstatic neuroendocrine tumours, causing a range of symptoms including frequent, severe bouts of diarrhoea. Approximately 14,000 people in the US have been diagnosed with carcinoid syndrome, with few treatment options available.2
Matthew Kulke, Director of Dana-Farber’s Program in Neuroendocrine and Carcinoid Tumors, which led the key trials supporting telotristat approval, commented that:
“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…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.”
Based on exit interviews with 33 Phase III trial patients, Dr Lowel Anthony, MD, Professor of Medicine, University of Kentucky concluded that:
“diarrhoea was one of the most troublesome symptoms and that any reduction in diarrhoea was meaningful, as it gave patients greater freedom, strength and quality of life.”3
Telotristat may cause constipation and patients should be monitored for severe constipation and discontinue treatment if they experience this.
The FDA granted the Telotristat application fast track designation and priority review, and the drug also received orphan drug designation.4
Telotristat is also at preregistration stage in the EU and Switzerland, with ongoing Phase III clinical development for carcinoid syndrome in additional countries. It was under Phase II investigation in the US and EU for the treatment of ulcerative colitis, but this appears to have been discontinued. Leixcon has entered into a licensing agreement with Ipsen, under which Ipsen can exclusively commercialise telotristat in countries outside of the US, Canada and Japan.