Hyperopia, I agree pretty much straight down the line with you. I am actually quite certain that poly iclc is not used as a “maturation agent” and have debated that previously with ATL. Recently ATL conceded it’s not true. There is no indication that is true or even that it makes sense, IMHO. It was always an adjuvant treatment when it was given, not used in “making” the cells for DCVax-L, and I honestly don’t think for other versions either. Reference in combination patents and other places is for broad protection and future variants. But no one here knows the actual special sauce of any manufacturing process other than the basics typically disclosed, and that’s the way it should be for purposes of IP protection. Claims to the contrary are puffery.
Also, Oncovir owns poly-iclc. And DCVax-L’s mechanism of action currently is about NWBO’s IP, not Oncovir’s. We don’t want them dependent on the manufacturer of another, expensive, artificially created compound that needed its own approval as a drug.
As for approval, it has been my argument that they will and must get DCVax-L approved on its own, because if not, it’s not a standalone drug at all. And further, the Phase 3 is DCVax-L without poly-ICLC, and the side trials are not completed, and are with an already approved set of other drugs in combination. Poly-ICLC is already an approved drug, and understood to be basically an adjuvant compound. Using an approved adjuvant with a vaccine that has been approved is not such a big deal that it needs literal approval. It will simply become the standard of practice / care, IMHO, given the immense results of the side trials. There have been 2 side trials with poly-iclc, the most recently published one is actually the 2nd side trial with poly-iclc. The third one is current and ongoing with Keytruda and the experimental part and DCVax-L with Poly-ICLC as the “baseline” or SOC in that combination trial that is partially funded by NIH. All of these results will be used for practical guidance once DCVax-L is approved and the data can be used to support the application for DCVax-L as validation of the method of action research. The company and doctors can argue that the method of action is being demonstrated and enhanced by this further research and depriving patients and doctors of the drug broadly would make no sense when it is obviously and demonstrably safe and has substantial evidence indicating strongly of a survival benefit for a broad array of patients both as a standalone drug and in combination with other, complimentary immunotherapies like Poly-ICLC, which by themselves are not proven effective at all against GBM or most other cancers. It is a very compelling case, regardless of the simian-like mud and feces throwing of shorts to suggest otherwise.
At one time I thought poly-iclc was not approved and speculated on approval of adjuvants with vaccines. But that is not necessary or relevant in the current mix of facts. The literature will be enough for any intelligent doctor to want to prescribe the two approved drugs together, IMHO. No need for special approval and RWE can ultimately justify the coverage by insurance and expansion of poly-iclc’s label. Also, adjuvant use and use of adjuvants with vaccines is not really a process that requires immense approval processes generally, when a compound is already generally approved for use and safe. So I do not worry immensely about that, at all. The processes will naturally be addressed and the companies, doctors, patients and regulators will all have a stake in seeing that move along smoothly.
Further, some of the others misunderstand RWE. It is for extending labels, and getting insurance coverage. The data does not need to be adequate to be an additional study or trial, that is exactly not the point. It is to show the benefit and enable the economics of combinations with already safe, efficacious and approved treatments at least in one area, to then extend the labels to other new areas and conditions.
So as for other cancers, compassionate use, as the company stacks up more patients with different cancers, they can work with the patients and doctors in that program to accumulate data to extend the label of an already approved DCVax-L.
So the current application is likely for at least GBM, possibly a broad array of brain cancers as previously the HE and other designations did recognize it as a potential treatment for a wider array of brain cancers even when the company was not asking for that.
But I do not see the approval as likely broader than that and it doesn’t need to be. Off-label prescription will likely expand because there are many patients who often are looking for a drug beyond what has been tried and failed previously, and DCVax-L will hit a lot of buttons, not the least of which is broad potential applicability, a powerful response with an almost impossible to treat type of cancer already, that it is quite a natural concept for treatment and makes sense immunologically, and because it has so few side-effects, for quality of life.
I think they will ultimately have plenty of RWE to extend the label, but that is something that comes after approval.
I agree re speculation about manufacturing and notions about other companies. It’s wild and not grounded in reality. The company already has what it needs for now. If a large partner materializes, great. But what those companies are building is for their own research and other treatments mostly having to do with mRNA vaccines.
I think some people want to keep chattering and developing clout on this topic, and so they speculate wildly, quite frequently. But the reality is, DCVax-L is a fantastic development by itself, and the combination trials are a further revelation and opening up of understanding about the pathology of cancer and the complex immune response to it. Lots of fundamental, new understanding is being revealed that will have broader implications for all research, and many drugs, by the work being done with DCVax-L. Will it all be monetized for us? That will be a complicated part of the process, but I do believe ultimately, DCVax-L will be used very broadly, by many doctors and patients for a broad array of cancers, but NWBO needs to get the initial approval first in various countries and Europe.
The rest will follow more naturally today thanks to reforms like the 21st Century Cures Act and innovations like RWE and ECA’s.
