As a followup to our interview with Northwest Biotherapeutics’ (NWBO) Chairman of the Board of Linda Powers, this article focuses on the “hard differentiators” between NWBO’s immunotherapy vaccine platform and that of their closest competitor Dendreon Corporation (DNDN).
Observers and investors of Northwest Biotherapeutics now believe the company’s DCVax may be poised to surpass Dendreon’s product in the field of vaccine based cancer treatments. Speculators have begun to rush back to pick up shares of NWBO just as sector darling Dendreon Corp. has lost 44% of its value after news that Dendreon can only make enough of their recently approved prostate cancer drug to treat about 2% of eligible patients.
First Factor: The Quality and Characteristics of the Antigens Used by Both Companies in Their Vaccines
Dendreon uses PAP, while NWBO uses PSMA. Terminology aside, what matters here according to representatives at NWBO is Dendreon’s target antigen is not expressed on all prostrate cancers. They have to screen their patients to see the expression of their target. NWBO’s target antigen is expressed on all prostrate cancers. Additionally, with Dendreon’s target, the level of expression goes down as the cancer progresses. The level of expression on NWBO’s target goes up as the cancer progresses. As we learned from NWBO’s Chairman Linda Powers, if your target is getting harder and harder for the vaccine to find and hit as the cancer progresses, that’s not the characteristic you want in your target antigen.
Another difference in the target antigens is NWBO’s target is bound to the membrane of the tumor cell. Linda Powers explains:
If the DCVax hits our target, it hits the cell for sure. Dendreon’s target is secreted by the cell, so while the target is close by, it is not necessarily bound to the cell in every instance. Antibodies can come along and glom onto to the target and not hit the cell itself, which means accuracy is an issue.
Second Factor: The Manufacturing and Purity of the Product
The active ingredient in both companies’ vaccines is dendritic cells. That is an active pharmaceutical ingredient, it’s the active agent that’s doing the job. But according to data provided by Northwest Biotherapeutics, the percentage composition of Dendreon’s product by the company’s own published material is 15% antigen presenting cells -- dendritic cells and others. According to NWBO’s published material, DCVax is over 80% active ingredient. The official product release criteria are over 80% and Northwest Biotherapeutics’ platform usually hits over 90%, thus the active ingredient in NWBO’s vaccine is much more concentrated.
Third Factor: How the Product Is Administered to the Patient
According to Powers, because there is such a low percentage of active ingredient in Dendreon’s vaccine, they have to deliver a huge volume, and the only way to do it is intravenous infusion, which is how they deliver Provenge to their patients.
This IV delivery can take over an hour. By contrast, because the active ingredient is so concentrated in the DCVax vaccine, NWBO only needs to administer a tiny volume of “just a few drops” and it’s administered with a simple injection under the skin, like a flu shot or insulin shot.
As is the case with most medications, where and how a vaccine is administered has a big effect on how well the vaccine can do its job once it’s put into patient’s body. The human body has a blood circulatory system and a lymph circulatory system which is separate and parallel. Dendritic cells do their job in the lymph system, in the lymph nodes.
According to Powers, Dendreon administers Provenge into the blood vessels, the vasculature, which makes it really hard for their vaccine to do its job, because before their Provenge dendritic cells can get to work, they have to first manage to get out of the blood vessels – which is a highly pressurized system, akin a 5 lane highway in rushhour – they have to get over to the side of the highway, get across the vessel wall and traverse across the tissue to get to where they can find the lymph node where they'll start doing their job. What happens is the majority of dendritic cells are lost along the way. You’re losing a lot of your product, and you’re just making it hard for the dendritic cells to do their job.
By comparison, NWBO administers DCVax as an injection under the skin, into the tissue, where the dendritic cells normally reside, which is nearby to the lymph nodes, which is where they go to do their job.
Again, how a vaccine is administered has a big effect on helping or hindering the product’s effectiveness in getting the job done.
NWBO’s clinical data shows significantly longer survival times than Dendreon’s and there appears to be a logical basis for that.
BioMedReports: When you talk about how the science works, does it matter whether you’re attacking brain or prostrate – is it basically the same thing?
Northwest Biotherapeutics’ Linda Powers: Yes. But let me flag one thing: the product version that’s for prostrate cancer is a little bit different than the product version for brain cancer and other cancers. The reason why is in a late stage prostrate cancer patient, you don’t have a tumor. There isn’t a tumor that you can go in and take it out and use that tissue to get the biomarkers and make the vaccine. The course of prostrate cancer disease is you get prostrate cancer in the first place, and then is when you have your surgery, they take the tumor out or they give you those radioactive beads that are implanted in the prostrate. That’s the beginning stage of the disease and the treatment. Then comes a long stage when you take female hormones to cancel out male hormones.
"Male hormones are like gasoline on the fire of prostrate cancer. The hormones are enough to keep the cancer contained, it’s a containment strategy. Keep it contained in the prostrate, not let it spread through the body, for anywhere from one to ten years. But sooner or later, pretty much all men fail hormones, and then you become a late stage prostrate cancer patient and that’s where both Dendreon and NW are focused, when the patients are so-called "hormone independent." When the hormones are no longer keeping the cancer in check and it’s starting to spread, and the only way we know that is because the PSA level is rising. You may have some metastasizes you can see on imaging – bone lesions – or you may not. But you don’t have like a focal tumor you can go in and take out and make use it. Therefore the prostrate version of DC Vax is made using a recombinant antigen, the PSMA.
"All of the other DC Vax products that have antigens are using a full set of antigens from the patient’s own tumor tissue, not a single antigen that’s made as a recombinant. That’s the difference in the product and the reasons why. But that’s also why it’s so important which antigen you choose, and those kind of characteristics that we talked about – is that antigen expressed on all the prostrate cancer or not? Do you have to screen the patients or not? – your choice of antigen is very important. It’s even more important when you’re only using one antigen than the whole set of antigens.
"To your point that this could work for everything -- putting aside the prostrate because that’s a special case because you don’t have a tumor – on the others cancers, where you’re using the biomarkers from the tumor, yes, absolutely. From everything we know about the biology, this same technology, this same product, the educated dendritic cells plus the whole set of antigens, the whole set of biomarkers from the tumor tissue, that should work on any cancer because all you’re doing is restoring the natural function, the natural power of the immune system that the tumor has been suppressing."
Disclosure: Author long NWBO