Telotristat Ethyl is an extremely significant introduction to the treatment of Carcinoid Syndrome diarrhea. It’s the first addition to the standard of care in more than 16 years and the first time an oral syndrome treatment has been developed. The drug was previously known as Telotristat Etiprate but was changed to Ethyl in Oct 2016. ‘Etiprate’ was previously a truncation of ‘ethyl hippurate’. The brand name is XERMELO®
Who is the drug for?
The drug may be of benefit to those whose carcinoid syndrome diarrhea is not adequately controlled by somatostatin analogues (Octreotide/Lanreotide). It doesn’t replace somatostatin analogues – it is an additional treatment alongside (although I have heard of patients in the US being subscribed who are not receiving somatostatin analogue treatment)
Where is it currently approved?
The US FDA approved the drug 28 February 2017. On 19 September 2017,the European Commission approved Xermelo® (telotristat ethyl) for the treatment of carcinoid syndrome diarrhea in patients inadequately controlled by somatostatin analogue therapy after the scientific committee of the EMA (known as Committee for Medicinal Products for Human Use (CHMP)) adopted a positive opinion recommending the approval of Xermelo® (telotristat ethyl) 250 mg three times a day for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy. The Ipsen press release is here. Clearly some action will be required in EC national countries before the drug becomes available through the appropriate healthcare systems.
Ipsen will pursue a worldwide regulatory plan for marketing authorisation submissions in the territories in which it operates. Once approved, Ipsen will be distributing the drug in all countries less USA and Japan where Lexicon retains the rights. Outside USA and Europe will be constrained by national approval timelines.
How does it work?
In the simplest of terms, the drug is an inhibitor of the enzyme tryptophan hydroxylase (TPH). TPH is the rate-limiting enzyme in serotonin synthesis which converts tryptophan (an essential amino acid which comes from diet) to 5-hydroxytryptophan, which is subsequently converted to serotonin, one of the main causes of carcinoid syndrome effects including carcinoid heart disease. The trial data indicates that Telotristat ethyl significantly reduced the frequency of bowel movements. Furthermore, it was also associated with “significantly reduced levels of urinary 5-HIAA“, a marker for systemic serotonin levels, which are typically elevated in severe carcinoid syndrome. Essentially it works by reducing the manufacture of Serotonin so it’s it may not have any effect on diarrhea not caused by syndrome (i.e. post surgery etc).
Resources for your perusal:
- You can read more about the trial data in a summary by Dr Matthew Kulke (Dana Farber) by CLICKING HERE (latest review from 2017 ASCO).
- There is also an excellent summary in video form by Dr Lowell Anthony (University of Kentucky) by CLICKING HERE. (“any reduction in diarrhea is meaningful“).
- An excellent technical description of the drug can be found by CLICKING HERE.
- The detailed output from the trial (results) can be found by CLICKING HERE.
- Great 2016 article from ASCO (American Society of Clinical Oncologists) can be found by CLICKING HERE.
- FDA Approval. CLICK HERE
- Lex Pharma press release on approval. CLICK HERE
- EU Approval (Ipsen Press Release). CLICK HERE
- The manufacturer Lex Pharma have established a dedicated site – CLICK HERE
Thanks for reading