There’s a lot of questions doing the rounds on forums and messages about the approval of Lutathera (PRRT) in USA, Europe and other places. The latest we know is in the red print headlines below. Followed by an update of known activity by region/country and a short primer for those not sure about PRRT.
ALL – 7 Dec 2017. Novartis and Advanced Accelerator Applications (AAA) Announced that Novartis is buying AAA and the process has started. Read here This will not have any effect on approval timelines.
EUROPE – 29 Sep 2017. AAA Announced that the European Commission (EC) has approved the use of Lutetium Lu 177 Dotatate (Lutathera®). Despite the treatment being used for over 10 years, this is apparently the first ever approval of the therapy. EU constituent countries are now free to fund and implement services. In the UK, now awaiting action by NICE (see announcement below 3rd and 11th Aug). Read here
USA – 28 Aug 2017. AAA Announced that the new Prescription Drug User Fee Act (PDUFA) date for Lutetium Lu 177 Dotatate (Lutathera®) would be January 26, 2018. Read here
UK – 11 Aug 2017. AAA responds to UK drug appraiser National Institute for Health and Care Excellence (NICE) negative recommendation. Read here
UK – 3 Aug 2017. Currently, NICE (the UK equivalent of FDA) are not recommending Lu-177 Lutathera based on cost. This is only a draft recommendation and another announcement is expected end Sep 2017. More to follow when known. This is a blow for patients in England. Read here
The situation is confusing – the therapy has been in use for some time
Of course, this therapy has been in use in Europe and some other places for some time but to be honest, they have been on a limited scale and never formally approved by national drug agencies. Despite it’s extensive use, the EU approval above is actually the very first approval of PRRT anywhere in the world. In UK, it was used for some time for those in need but was removed from routine availability through a ‘slush fund’ formally known as the Cancer Drugs Fund – to cut a long story short, the funding source was cut off. There are still ways of obtaining the treatment pending formal acceptance by the NHS but certain criteria apply.
In the meantime, I constantly see stories of patients travelling to Switzerland, Germany, Netherlands, Sweden and England. I’m sure there’s people travelling to other countries! However, it does indicate one thing, there is a huge unmet need in that many patients do not have access to the best treatments in their own country. I see this daily through many private messages.
Europe (EU associated countries)
The European Medicines Agency (EMA) “market authorisation” received a positive indication on 20th July followed by EC approval on 29 Sep 2017. The positive indication reads “Lutathera is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP NETs) in adults”. Of Course, the decision to fund the drug will be with national approval organisations.
Despite the EC approval on 29 Sep 2017, NICE are currently not recommending PRRT (Lu-177) due to what looks to me like cost grounds. One theory is that this is a metaphor for price negotiation between NHS and AAA. This is a particularly controversial issue for UK as the drug was removed from routine use (Cancer Drugs Fund) in 2015. Why wait in UK? There are ways to get access to PRRT via different funding sources. Ask your specialist because this possibility is unfortunately not very well publicised. PRRT is funded in Scotland, Wales and Northern Ireland. NICE only covers England.
The situation in USA looks more favourable, most likely due to the different healthcare system in place …. although whether insurance companies will be quick to sign up, is another question. My guess is it will be approved by the FDA on or before 26 Jan 2018.
Why wait in USA, there’s an extended access program in place (click on the highlighted link to see locations).
PRRT is only available at a few cancer centres in Canada. It can only be used with special approval from Health Canada or by taking part in a clinical trial
Australia seems to be ahead of the game or that is what I sense when I read output from there. There’s a good section on the Australian effort – click here.
These guys have had to fight to get some progress on the provision of PRRT. Currently New Zealanders have to go to Melbourne Australia for treatment – almost 50 New Zealanders with NETs are currently raising tens of thousands of dollars to pay for treatment in Australia because the life-prolonging treatment isn’t available locally. But this could change in 2018. On 21 Nov 2017, Unicorn Foundation New Zealand announced that Pharmac, the New Zealand government agency that decides which pharmaceuticals, have recommended that PRRT be funded for patients with medium priority for the treatment of unresectable or metastatic, well-differentiated NETs (irrespective of primary site) that express somatostatin receptors. This recommendation will be discussed at the PTAC meeting Feb 2018.
- Pretoria – Steve Biko Academic Hospital and the University of Pretoria
- Johannesburg – The Wits Donald Gordon Hospital
- Durban – Umhlanga Molecular Imaging and Therapy Centre of Excellence at Umhlanga Hospital
Middle East, Asia and the Far East
Turkey – Istanbul, Dr.Levent Kabasakal.
India – Mahatma Gandhi Cancer Hospital, Visakhapatnam. Recently started radionuclide therapy. Although only currently available privately, some patients have been sponsored by the companies that they work for. Point of contact is Dr. K. Raghava Kashyap.
Short PRRT Primer
For those who are still not sure what it’s all about. This is a non-surgical treatment and is based on the use of somatostatin receptors to attract a ‘radiopeptide’. It is normally administered intravenously. The radiopeptide is a combination of a somatostatin analogue and a radioactive material (radionuclide). As we already know, somatostatin analogues are a NET cell targeting protein, so when combined with the radionuclide, it binds with the NET cells and delivers a high dose of targeted radiation to the cancer while preserving healthy tissue. Simple!
PRRT will not work on all NETs and not everyone will suited to this treatment. For this treatment to be successful, you must have somatostatin receptors in your tumors. Success rates are not 100%.
Understanding the terminology is half the battle in understanding the latest radionuclide developments. I’ve included Ga-68 PET scans as the term ‘Theranostics‘ is becoming a commonly used theme.
LUTATHERA is the radionuclide ‘mix’ for use in Peptide Radio Therapy Treatment (PRRT). It is still waiting for approval in USA. The delay is due to an issue with the data which has now been resubmitted. You may also see this drug called ‘Lutetium’ or ‘Lu-177 dotatate’, or just ‘Lu-177’ on its own. Yttrium 90 (Y-90) is a radionuclide also used in PRRT.
NETSPOT is not PRRT but is the radionuclide mix for use in Gallium 68 (Ga-68) PET diagnostic scans and was recently approved in USA. SOMAKIT TOC is essentially the European equivalent of NETSPOT and is approved in Europe.
Together they form a ‘theranostic pair’. Theranostics is a joining of the words diagnostics and therapy. Theranostics is apt as together (NETSPOT / SOMAKIT TOC and Lutathera), both target NETs expressing the same somatostatin receptor, with Lutathera intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version.
Moreover, thanks to the theranostic approach that nuclear medicine allows, AAA’s NETSPOT/SomaKit TOC products will be able to determine when Lutathera is the appropriate treatment.
What’s next for NETs PRRT?
- two radiopeptides together;
- radiopeptides in conjunction with other chemotherapies (check out my article PRCRT);
- repeated administrations of the radiotherapies;
- other radionuclide-peptide combinations (….article to follow);
- increasing the number of indications for this therapy, including other disease targets;
- e.g. they are already using it for Prostate Cancer.
- e.g. new radionuclides – see my article about the COMPETE trial.
Thanks for reading