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Telotristat Ethyl is an extremely significant introduction to the treatment of Carcinoid Syndrome. 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 is not adequately controlled by somatostatin analogues (Octreotide/Lanreotide). It doesn’t replace somatostatin analogues – it is an additional treatment.
The US FDA approved the drug 28 February 2017. The European Medicines Agency has also accepted the filing for Telotristat Ethyl as an adjunct (i.e. in addition) to somatostatin analogue therapy for the long-term treatment of carcinoid syndrome.
In addition to the European submission, 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. The approval estimate outside USA is not yet clear but my best guess is that the EMA approval should be later in 2017 and then subject to local regulations for access to treatment and reimbursement. 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.
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“).
- The 2016 ENETS conference also indicated a knock on effect of reducing the risk of, and perhaps even halting Carcinoid Heart Disease. You can read about this by CLICKING HERE.
- 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
- The manufacturer Lex Pharma have established a dedicated site – click here
I know some patients who participated in the trial and they seem to be positive about the drug – if anyone can make a comment, that might be helpful to others who are thinking
We all know that Neuroendocrine Tumours (NETs) and their syndromes are complex but there is even more complexity to be found in a group of related disorders known as Multiple Endocrine Neoplasia (MEN). Until I read up for this post, I hadn’t fully realised how closely related the two conditions are. I would now recommend that all NET patients should try to understand the basics of MEN and vice versa, particularly as both conditions seem to come with a plethora of endocrine related effects.
MEN patients will normally have a tumour in at least two endocrine glands – thus the terms ‘Multiple’ and ‘Endocrine’ (tumours can also develop in other organs and tissues). Neoplasia is just another name for tumour and these can be non-cancerous (benign) or cancerous (malignant) with the potential to metastasize.
MEN syndromes can comprise varying combinations of tumours. So putting the heredity aspects to one side, it’s potentially an extremely challenging diagnostic scenario. To add to the complexity, some of the associated tumours can be sporadic (non hereditary) classic Neuroendocrine Tumours in various locations.
MEN is actually an umbrella term for a number of types (syndromes) of the disease – MEN1, MEN2 (2a and 2b (2b was formerly MEN3)) and Familial Medullary Thyroid Carcinoma (FMTC). There is a new kid on the block called MEN4 which is extremely rare. In the most basic of terms regarding tumours, MEN1 seems to be centred on tumours of the parathyroid glands, the pituitary gland, and the pancreas (the 3 P’s) with MEN2 mainly focussed on the thyroid. MEN4 is similar to MEN1 but caused by mutations in a different gene.
What is particularly distinctive with MEN is that they are inherited disorders (familial). That means that they can be passed down in families, with each child of an affected parent having a 1 in 2 or 50% risk of inheritance. Consequently genetic screening/testing is normally undertaken in established MEN families and those at risk of MEN.
You may also have heard of other rare NETs with a familial aspect, in particular Pheochromocytomas (adrenal gland tumours) and Paragangliomas (outside the adrenal gland, less common and not all are inherited). These tend to be grouped under MEN for support and advocacy.
- AMEN Support where there is a useful Primer Leaflet
- A great video from Dr Mark Lewis who is an Oncologist and MEN patient. This is great as he speak as both! Click here to watch
- More technical information can be found on the NIH site here including the genetic aspects.
- For patients, there is an excellent support group forum here – Join the AMEN Support patient support group.
I’m grateful to my friend and MEN patient Linda Hageman for supporting my blog activities and also for allowing me to join the AMEN support group to learn more. This is one of the friendliest and well run support groups I’ve seen. On this site, you will find Dr Mark Lewis, an Oncologist and MEN patient who supports Linda (who is a Nurse) with a ‘Ask the Doctor’ section on their website.
Having just researched the whole subject, I now better understand the basics of MEN and linkages between MEN and NETs. I now know why there is such a close bond between the patients and advocates of both. In fact, I have met many patients on forums who are both NET and MEN.
This is a really complex but interesting subject so I’ve suffixed this post ‘Blog 1’ with the intention of exploring further in the coming weeks.
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