1st Aug 2020 update
In a move that Lexicon Pharmaceuticals Inc. chief Lonnel Coats said will focus the company on its phase II neuropathic pain program, The Woodlands, Texas-based venture has agreed to sell one of its two approved products, the carcinoid syndrome diarrhea therapy Xermelo (telotristat ethyl), to Tersera Therapeutics LLC
I don’t expect this to make any difference to the drug or its supply. Business as usual. The outer package may change to reflect new owners but the brand name XERMELO will most likely be part of the sale.
Read the news from Lex Pharma – click here.
Telotristat Ethyl is a 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®
UPDATE MARCH 2018
The March 2018 issue of Clinical Therapeutics provides the first report of the effects of XERMELO on changes in weight in patients with neuroendocrine tumors (NETs) and carcinoid syndrome that participated in the TELESTAR study. You have to remember that XERMELO is approved for those with carcinoid syndrome diarrhea not adequately controlled by somatostatin analogues (author’s note – i.e not for diarrhea caused by (say) side effects of surgery).
Of the 120 patients with weight data available, up to 32.5% of patients treated with XERMELO experienced significant, dose-dependent weight gain (≥3% from baseline). Only 5.1% of patients on placebo experienced weight gain. Importantly, patients with weight gain experienced improvement in carcinoid syndrome control, as seen in reduction of bowel movement frequency and in parameters of nutritional status associated with positive changes in patient-reported outcomes compared with patients with stable weight or weight loss. Those patients also experienced reduced u5-HIAA levels. Patients with weight gain also experienced fewer serious adverse events than patients with stable weight or weight loss.
(see link below)
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.
This does not mean all EU countries will use it. Clearly some action will be required in EU national countries before the drug becomes available through the appropriate healthcare systems.
On 17 Oct 2018, Health Canada announced approval for Canadian NET patients – click here.
UK. 8th January 2020. NHS England did not approve Xermelo with the following statement:
“NHS England has carefully reviewed the evidence to treat CS diarrhoea with telotristat. We have concluded that there is not enough evidence to make the treatment available at this time”. NHS Scotland and Wales have authorised it for “Restricted use”. Restricted use means a narrow meaning to the approval, perhaps a particular subset of patients who would benefit most. There is no data for Northern Ireland.
For all other countries please note that 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“).
- 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
- 2018 revised clinical data – CLICK HERE
Serotonin Video with myself and Dr Mike Morse
I made a video in 2019 with Dr Mike Morse sponsored by Lexicon Pharmaceuticals, Inc. It’s all about Carcinoid Syndrome with a slant towards hormones, in particular Serotonin. Entitled “Likely Suspects: How Hormones May Lead to Carcinoid Syndrome – What People Living With Carcinoid Syndrome Need to Know”
You need to register to watch although some of you will already be registered and just need an email to login to see the this webcast. The one I’m featured in is the latest in a series on the subject and I’d like to break the record for views please! Please help me achieve this I would also love to get your feedback and sincerely hope you will find the time to listen in. Please also find the time to complete the survey at the end. Thanks
Click on the link here: www.CarcinoidWebcast.com
Don’t forget to press the play button and ensure your sound is turned up, particularly on mobile devices.
Thanks for reading