UPDATED 11 Aug 2017. AAA responds to UK drug appraiser (NICE) negative recommendation. Check out this article which also updates on the US FDA submission – I quote “Last month the company re-submitted its new drug application to the US Food and Drug Administration (FDA), having received a complete response letter from the agency in December 2016, highlighting issues with the way trial datasets were submitted. AAA is confident that it has now addressed these issues and is awaiting a Prescription Drug User Fee Act date from the FDA.”
UPDATED 3 Aug 2017. Currently, NICE (the UK equivalent of FDA) are not recommended Lu-177 Lutathera based on cost. This is only a draft recommendation and comments are required by 24 Aug. More to follow when known. This is a blow for patients in England. Read more here.
Original post continues …..
There’s a lot of questions doing the rounds on forums and messages about the approval of Lutathera (PRRT) in USA but I know nothing about an anticipated approval date. Negotiations are still ongoing between US FDA and the Lutathera manufacturer Advanced Accelerator Applications (AAA). A pharmaceutical media outlet today published an interview with the CEO of AAA which has prompted this post. Whilst there is no indication of date mentioned, I’ve placed a link to it the end – it’s more commercial than medical related but some will find it interesting. For those who are not aware, AAA is the manufacturer of diagnostic and therapeutic radionuclide drugs for use in Neuroendocrine Tumors and other cancers. Note: The CEO of AAA just announced on 21st July 2017 that “the revised Lutathera (PRRT) NDA would be submitted to the USA FDA this month” (after note – it was submitted 27 July). And in Europe, the EMA “market authorisation” received a positive indication on 20th July and once the marketing authorisation is in place, the decision to fund the drug will be with national approval organisations.
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”.
This is particularly important for UK where National Institute for Health and Care Excellence (NICE) removed the drug from routine use (Cancer Drugs Fund) in 2015.
Why wait in USA? There an extended access program in place
For those in USA, you may still get access to PRRT via the Extended Access Program (a form of clinical trial) and the list of providing centres and details of the program can be found by clicking here.
Why wait in UK? There are ways to get access to PRRT via different funding sources. Ask your specialist.
Of course, these diagnostic and treatment tools have been in use in Europe for some time but to be honest, they have been on a limited scale. In UK, it was even removed from routine availability through a ‘slush fund’ formally known as the Cancer Drugs Fund – to cut a long story short, that dried up. There are still ways of obtaining the treatment but certain criteria apply. Hopefully it will be reintroduced to England soon. In the meantime, I constantly see stories of US patients travelling to Switzerland, Germany and England; and Irish patients travelling to Sweden. I’m sure there’s people from other countries also travelling to other countries! It really is an international disease! 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.
Understanding the terminology is half the battle in understanding the latest radionuclide developments. I’ve included Ga-68 PET scans in this and you will see the linkages as you read on.
NETSPOT 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 already approved in Europe.
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. To the best of my knowledge, there is no new forecast decision date for approval (……I have a view it might arrive at quite short notice). You may also see this drug called Lutetium or Lu-177 dotatate.
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.
You can read a previous update of AAA’s approach to diagnostic and therapy tools for NETs by clicking here.
NETs leading the way
While AAA has no plans to partner on Lutathera for future indications, it may continue doing so, and the next pair of drugs it is seeking to bring to market, 177Lu-PSMA-R2 and complementary diagnostic 68Ga-PSMA-R2, is addressing prostate cancer, so a much larger patient group. Already this approach is showing promise in Germany. German laws allow sometimes faster access to novel technologies in the field of nuclear medicine, and so there has been an uptake of the diagnostic examination. AAA believes many thousands of patients have been already diagnosed using a PSMA-guided compound.
Here’s an extract from AAA’s development timeline
177Lu-PSMA-R2 and 68Ga-PSMA-R2. 177Lu-PSMA-R2 and 68Ga-PSMA-R2 are in development to treat, image, monitor and stage prostate cancer. 177Lu-PSMA-R2 will be aimed at treating and monitoring prostate cancer and 68Ga-PSMA-R2 should act as its companion diagnostic and help diagnose and stage the disease. AAA has signed an exclusive license agreement with Johns Hopkins University in Baltimore, Maryland to develop and market PSMA-R2, in prostate cancer.
177Lu-NEOBOMB1 and 68Ga-NEOBOM1. NeoBOMB1 is a unique new generation antagonist bombesin analogue targeting GRPR-expressing malignancies. Our plan is to radiolabel NeoBOMB1 to develop a theragnostic pair: 177Lu-NeoBOMB1 for treatment and a 68Ga-NeoBOMB1 for diagnosis. AAA has signed an exclusive license agreement with Erasmus University Medical Center (UMC) and Demokritos National Center for Scientific Research to develop NeoBOMB1. AAA is currently planning three clinical studies in different indications including gastrointestinal stromal tumors, prostate cancer and breast cancer.
Advanced Accelerator Applications (AAA) – from Hadron Collider to Neuroendocrine Tumors
The company is already a European leader in the production and commercialization of molecular nuclear diagnostic radiopharmaceuticals for positive emission tomography (PET) and single-photon emission computed tomography (SPECT), but it could make waves in different circles with this unique strategy – integrating diagnostics and therapeutics.
Big pharma is likely to have an eye on AAA’s theranostic approach to neuroendocrine tumors (NETs), involving imaging of NETs expressing a specific somatostatin receptor using the company’s NETSPOT/SomaKit TOC diagnostics, and treatment of such tumors using its therapeutic, Lutathera (Lutetium Lu 177 dotatate).
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 to the diagnostic.
While NETSPOT and SomaKit TOC are already approved in the USA and Europe, respectively, Lutathera applications are currently under review, with orphan status, by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
If AAA was to reach the market with Lutathera, the company’s route to becoming a drug developer would be an unconventional one.
It was set up by Mr Buono, a physicist by background, in 2002 to develop a patent from the European Organization for Nuclear Research (CERN) in the radioisotope production field.
“This opportunity gave me the possibility to understand the nuclear medicine market and at that time a new modality of imaging was explored – that was PET,” he recalls.
“The drug for that modality, that had to be injected into patients for the imaging, was complicated to manufacture. You needed a particle accelerator, and they had only a 10 hour shelf-life, so it needed a completely new model. I took the challenge to create an industrial model for those drugs in Europe – we had only a couple of examples of companies in France at that time and the rest was only academic manufacturing and use.”
Read the full interview here
““We really want to become big in this field – at the moment we are kind of alone but I think that will not be so for long because I think that the NETSPOT/SomaKit TOC and Lutathera example will be enlightening for many people.”
Let’s hope so.