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Dr K may have investors ready to pitch in another tranche to bring them to IDE approval if needed.
IDE submission/approval most likely 2Q23. It could happen 1Q23 but I doubt it, given the pace.
Do your own research. You will not be convinced otherwise.
As for the RDGL dose we know that:
Alle Ding sind Gift und nichts ohn' Gift; allein die Dosis macht, das ein Ding kein Gift ist.
However, the history of cancer drug development has been to try and push the dose as high as possible to maximize efficacy. The tolerance for side effects is much higher than for diabetes or CV drugs. Let's see what comes out of the rabbit studies and how the data will be used.
Everything has come a long way! I've been in the drug discovery business a long time and things are lining up very nicely for a successful clinical development. The premixing was a brilliant idea that will significantly simplify the procedure. I am hoping the new dosimetry data from the rabbit studies will allow to increase the Y-90 loading and totally nuke these tumors into oblivion!
There has been a rise in cancers of all kinds since introduction of the Covid vaccines (some are fast growing solid tumors). It may be that RDGL will be available just at the right time for some of these patients.
The FDA suggested the EFS because they want to see this going to the clinic faster so I am not worried about IDE approval at all. BDD and IDE are not the same.
There won't be a comparative control. I work with 5 clients in oncology and none of the PhI studies have a control. That is not how it's done.
The FDA suggested an Early Feasibility Study pathway. This means that the device doesn't have to be in its final design (see: https://www.fda.gov/media/81784/download and https://www.fda.gov/media/86975/download). It also means that they may only need a few patients for the first EFS (5-12). Depending on the outcome they could even move directly to the pivotal study since RDGL is basically in its final form and they have a great non-clinical profile.
If properly executed, the clinical development program could advance much faster than what some on this board think: On a recent program we filed an IND in September and by December we already had 5 patients on study. Things could move quickly after IDE approval. The Mayo clinicians may already have potential patients in mind.
FDA approval is absolutely not iffy. RDGL works. It doesn't care about cancer genetics, tumor heterogeneity, drug metabolizing enzymes polymorphisms, or drug-drug interactions. Some of these issues have killed many projects or even companies (first-hand experience). This just won't happen with RDGL.
Gotta keep it real!
The FDA had agreed on an expedited review so I anticipated 30 days. Nothing atypical here.
I don't remember having a meeting canceled. However, the requests have never been as simple as a approval of a non-clinical dosimetry study protocol.
It is unlikely the meeting will be cancelled. If a written response was enough the FDA would have told them so after submission and the meeting would not have been scheduled.
If this is a typical FDA interaction, Dr K should get a written response this week or Monday at the latest. He will know then whether they agree with the study plan.
The FDA may not have been satisfied with the quantitative aspect of the existing containment studies using PET. Thus the need for additional data using a more sensitive/quantitative method to assess distribution to adjacent tissues (https://pubmed.ncbi.nlm.nih.gov/8358356/). Based on the (limited) details of the study shared by Dr K, this may be all that is requested.
MK reminds of the tortoise in La Fontaine's fable. Slow but steady... and won the race!
0.5 pps after IDE approval 2Q23. A 3x jump after that is not impossible based on positive updates.
We could be there one year from now.
Yes, it is classified as a device (as that may be a good thing) but in essence it is a drug. They may be late in the game, but it's early in the clinical development (they haven't even started!). Until now it was all non-clinical.
Gel integrity/performance after mixing can be easily assessed in vitro. Many product changes are approved this way.
If the FDA doesn't like the pre-mixing then they don't have to pre-mix. No delay.
And who knows, it may have been the FDA who suggested the pre-mixing.
More nonsense. The product is not approved and it's not late in the game. They are only starting. Have you ever developed a drug? I have been on programs where the drug product changed 3 times in the course of development and it was never back to the beginning with the FDA.
Y-90 is also produced in the Netherlands.
https://www.advancingnuclearmedicine.com/en/products/yttrium-90
Vivos is working with a global provider of Y-90 phosphate (can't remember the name). Should not be an issue.
The vet was Dr. Olivier Keravel of Eiffelvet. He has only one clinic in Paris, specialized in oncology (https://www.eiffelvet.fr/).
There are set timelines for FDA responses to meeting requests:
https://www.fda.gov/media/114034/download
We may have to wait until end of October/early November unless they accelerate the review.
Dr K clearly stated that the tumor was "currently of pea size" which meant the implantation was successful and the tumor was growing. I see a lot of xenograft tumor growth data and I thought this was a very positive update.
I've spent many years in academic research and some procedures require "tricks" that don't always appear in the experimental section of publications. Obviously the JHU scientists haven't used this model (I see nothing recent in the literature) and they had to learn. Please give them a break!
JHU may already have used the tumor from the first rabbit to inoculate more rabbits. That is the only way to keep a supply of fresh cells. I hope they use some of these rabbits to run a pilot study while waiting for the FDA's approval of the protocol.
Growing tumors from frozen VX-2 cells can be a challenge (33% success, https://pubmed.ncbi.nlm.nih.gov/24834491/). However, for the next round of inoculations JH will now have fresh cells available that have a much higher success rate (~90%).
You are correct.
Per May 24 update:
"The test is straight forward. We will induce VX-2 tumors in rabbits and then measure the activity over time using PET/CT to show, once again, that the Y-90 stays at the injection site. We will then euthanize the rabbits and quantitatively measure the remaining activity in the tumor using very sensitive counters and compare it to the starting activity corrected for decay."
Unfortunately my answer is: It depends... I am currently reviewing a bunch of reports for a submission. One CRO has an amazingly fast turnaround time. Another one is excruciatingly slow and we had to make some calls to speed up the process. JHU is not a CRO with templates so it may take time to generate, review, revise, and finalize this report. In some cases when the FDA had very specific questions we have submitted unaudited reports to the FDA to save time. Dr K. may not go that route.
I know. That doesn't mean they had to. Dr K may be too conservative.
RDGL doesn't have to request for a meeting. I was involved in more than one case when the FDA wanted additional data. Once we had them, we sent them. The answers were typically: Thank you, you can proceed. Unless we had uncovered something problematic which needed discussion.
I was involved in three IND submissions to the FDA this year alone, and more coming, so I have experience working with them. This doesn't look like "starting over" since the FDA is not asking for efficacy data. The previously submitted containment studies may be lacking in some aspect(s) that hopefully the VX2 rabbit study will address once for all.
I would not be surprised if JHU is running a pilot study in rabbits prior to submission of the final protocol to the FDA. Given the importance of the study that would be a wise thing to do.
From the Sep 20, 2021 press release:
This filing is an important milestone for Vivos and reflects the efforts of numerous parties. In particular, we are pleased that this IDE filing included the Mayo Clinic Clinical Trial Protocol for Radiogel ™ , which is currently being reviewed by Mayo’s Independent Review Team.
From the FDA website for a Nonsignificant Risk Device:
"The FDA considers an investigation of a nonsignificant risk device to have an approved IDE when the IRB concurs with the nonsignificant risk determination and approves the study"
Would you expect less for a Significant Risk Device?
Everybody is forgetting IRB approval of the clinical protocol, about which we haven't heard a single word...
I have three submissions planned for this summer. They are not on vacation!
Better "one guy in a lab" with a product that works and that is ready for commercialization in its current form than a biotech with 50 employees working on a novel mechanism with sub-optimum chemical matter yet to be turned into a drug product and with an unknown safety profile.
This is Vivos' problem. Not the FDA's.
I think your are misinterpreting "Always more work to be done and evidence of this is continually shining through the performance of #IsoPet". This means that, as they increase the number of pets treated they are learning more about the potential of IsoPet/RadioGel and hence there is more work to do! IMO this is actually an encouraging note and not related to the IDE.
Yes it was 1:8. They called it a "gentle" RS.
The FDA is not to blame here. They proposed the EFS IDE which means they want to see Radiogel go into humans. Otherwise they would not have suggested that option.