THE COMPETITIONI had been studying the FDA approval...

THE COMPETITION

I had been studying the FDA approval process/data/analyses for the 2 competing NETS diagnostic products that are in the market, when Clarity dropped the video where Alan specifically mentioned the trial that was done for one of the products approval. I instantly remembered UpsideDownUnder asking (or questioning) if I was a paid Clarity pumper - if I was, then Clarity would have warned mee in advance, wouldnt they? Or perhaps, I have been fired!

Anyway: Great stuff, I think! I know that it can be frustrating when we want to know more, but my view is that Clarity is one of the best (if not the number 1) at communicating about the products (investor education - those videos), and on providing strategy updates! Yes, there are secrets - but thats the whole poit - secrets must stay secret! Who, reveals mor ethan Clarity - I can't think of any right now!

I think its important for us to understand how others got where we are headed, particularly now that Clarity seems to be committed to going all the way to revenue!

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Product 1: NETSPOT (68Ga-DOTATATE)

The product that Cu64-SARTATE was pitted against in the DISCO Trial, 68Ga-DOTATATE, is called NETSPOT (or a version of it). NETSPOT is owned by Advanced Accelerator Applications (a Novartis company). It is FDA, EMA, and TGA (+ others) approved, and is the number 1 used product in NETS PET/CT diagnosis, with 70% of the market.
NETSPOT was FDA approved in 2016 via the 505(b)2 regulatory pathway. Its the Illucix equivalent for NETS.



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Product 2: DetectNET (64Cu-DOTATATE)

Alan mentioned DetectNET, which was the first and only Cu64 radiopharmaceutical product to have got FDA approval so far (Cardinal Health). The approval was in 2020. Clarity will thus follow in the footsteps.

Here is something important that the FDA said in a specific section (as per approval documents) - regarding the Cu64 radionuclide;

• The current NDA is the first to be submitted for an imaging drug labelled with a copper radionuclide.
• Cu-64 has a half-life of 12.7 hours, which enables manufacturing of the drug product centrally and distribution to other parts of the U.S. (without dependence on Ga-68 generators.)
• The relatively long half-life of Cu-64 also facilitates delayed imaging after drug administration.
• The lower mean positron range, or distance a positron travels from emission until annihilation, is shorter for Cu-64 (1 mm) compared to Ga 68 (4 mm). A shorter range theoretically results in increased spatial resolution. (Kjaer and Knigge 2015).

Elsewhere on the same document, the FDA also says: "The half-life of Cu-64 also facilitates delayed imaging or repeat imaging without redosing in cases of image acquisition issues such as patient movement during scanning..."

We should expect these words which are contained in the FDA approval document for DetectNET, to be repeated again in the Clarity applications to the FDA - for those special statuses that we love (Fast Track, Breackthrough, Accelerated), and again on filing for approval! And, this is just about the advantages of Copper 64 - and not the clearly superior Super STAR: SAR, the cage that to date, has now been used and proven safe in over 500 patients (from my estimation);

• # 250+ patients on the SAR-bisPSMA products trials (PROPELLER, COBRA, SECURE, CLARIFY, AMPLIFY, and Co-PSMA),
• # 230+ patients on the SAR-BOMBESIN products trials (C-BOBCAT, BOP, SABRE, COMBAT), and,
• # 65+ patients on SARTATE trials (CL01 - NETS, CL02 - Meningioma, DISCO - NETS, C04 - Neuroblastoma).

My view based purely on the logic thats in my head is that hese numbers will collectively add to the body of evidence of safety, and may well be used in supporting FDA filing applications of all of the products in this group with regards both the SAR component (the platform) of the products, as well as the construct: 64Cu-SAR! That to me shows we have covered a lot of ground. It can further be argued that Copper 64, on its own, has passed many safety tests via its use elsewhere, including use with DOTATATE products, such as those that led to DetectNET gaining FDA approval.



Radiomedix did just one single arm registrational trial (RMX-18-22). It's important to note that the trial enrolled just 42 actual patients with prior NETS (37 patients) or suspected NETS (5 patients - just 4 had evaluable data)! The other 21 were healthy volunteers with no disease. An earlier dose determining study had 12 patients, and some of them got included in the pivotal trial of 42 patients + 21 volunteers!



COBRA, at 45 actual patients with known or suspected NETS, had more cases than what Radidomedix had in the only P3 trial that was done for this approval.

Radiomedix also utilised some historical data which they reanalysed - considered poor quality but useful and supportive. BUT the FDA said the following;"... While certain weaknesses are present in the two studies, the shortcomings are outweighed by the robust imaging efficacy results, particularly given the orphan drug population for which the product is intended. Additional factors to consider are the physical characteristics of Cu-64 as a radiolabel and the history of extensive clinical experience with multiple somatostatin analogs for both diagnostic and therapeutic purposes in patients with NET ..."

Also worth noting is that, per the DetectNET label from the FDA, image acquisition is at 45 to 90 minutes, which would seem to limit the Cu64 half-life advantages!



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The future: Cu64-SARTATE
I expect;
a) Clarity to seek approval via 505(b)1 regulatory pathway, which is for completely new drugs. This would mean that Clarity will need to run their own trials, including a P3.
b) The FDA to not ask for a comparison arm: it will likely be single arm trial like CLARIFY and AMPLIFY. The numbers will likely not be as large as those for 64Cu-SAR-bisPSMA either - superiority against SOC helps lower the numbers, and there will be precedence as well thanks to DetectNET. An important matter here is that the disease is rather rare so it is reasonable to ask fo asmaller sample size.
c) I expect it will be a matter of demonstrating certain levels of Sensitivity and Specificity (or Sensitivity and Negative Predictive value as opposed to Specificity).

To cut the long story short; The bar for FDA approval is nice and LOW!

For interest - here (below) is a table showing Ga68 and Cu64 decay rates.


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REFERENCES

Cardinal Health - FDA-approved radiopharmaceuticals
DETECTET label.pdf
NETSPOT label.pdf
NETSPOT (Ga68-DOTATATE) FDA Approval Document.pdf
DETECTET 213227Orig1s000MultidisciplineR.pdf