The just released article in seekingalpha comments about the promise of immunotherapy and explains why Prima' technology for harvrsting cells and which Is delivered inter dermal is better than Dendreon's intravenous delivery.
It also states that because the immune system takes time to build, you want to wait and see overall survival, rather than interim results as the difference will show with more time.
I have reproduced relevant abstractswhich directly mention Prima:
BN - If immunotherapy products are so effective, then why is it that Dendreon has encountered so many problems from a clinical point-of-view?
RJ - Dendreon had such a rough and tough "guinea pig-like" development pathway. They didn't know what they were doing. They were giving injections intravenously and that's why their product is really not optimal. It only has a small number of dendritic cells, 10% harvested cells; they didn't develop it the right way. When Dendreon began it was during the early stages of harvesting dendritic cells, and we were still learning how. They just did it wrong.
BN - I've always heard that monocytes were one of the primary reasons for Dendreon's failures. Why wouldn't they go back to the drawing board with the same technology and test the drug after harvesting a greater number of monocytes?
RJ - The reason they can't go back and do that is because their IP doesn't allow them to do it. If they wanted to do that, they would have to begin a whole new process of development, start-from-scratch. For them, it's going to be six or seven years before they could get to that point. They can't go back and use another harvesting process because other companies have gotten an IP, and Dendreon's only covers its process. They would be infringing on someone else's intellectual property if they harvested more dendritic cells. Another problem with Dendreon is that they harvest intravenously; so with that kind of approach you want to do it intradermally, but they can't because of their IP.
When Dendreon was going through its trials and tribulations with the FDA and developers, there were others who already had a better therapeutic approach. Today, Argos Therapeutics and ImmunoCellular Therapeutics (IMUC) have a better approach; even a company such as Prima BioMed has a better approach.
I have not covered ImmunoCellular Therapeutics in detail. I know the company well, but in terms of the number of dendritic cells harvested, they are definitely above 70-80%, as is Argos. With this approach, you are getting far more product in the immune cells and are able to have less boosters, less injections, making it clearly a more streamlined approach. And what ImmunoCellular Therapeutics, Prima BioMed, and Argos do is have their own manufacturing system that is better than Dendreon's whose cost-of-goods are higher because there are more steps in the process. This is one of the biggest improvements that we've seen with the new second-generation approaches in immunotherapy.
BN - Going back to Dendreon, since the company can't mature monocytes into dendritic cells at a higher purity, do you think the company will acquire one of the earlier-phase companies with a strong patent portfolio that have the ability to harvest at higher levels? Specifically, ImmunoCellular Therapeutics has a market cap of just $130 million; it could be acquired cheap and could lead Dendreon to profitability, right?
RJ - The Dendreon IP is for their protocol and if Dendreon has to use another approach irrespective of their IP, they would have to redo all their clinical trials - not practical since (Provenge) is already on the market. Yes second generation dendritic cell approaches are better at harvesting more Dendritic cells and also better in how they deliver - intradermal v IV. IV is a poor way for Dendreon to deliver Provenge. Intradermal is better in presenting the antigen to the immune system.
I think the acquisition of immunotherapy needs robust clinical trial data - maybe beyond Phase II. And if the data is really good, then the market cap will not be $130 million.
BN - A lot of these "second-generation" immunotherapy companies will be announcing data this year, including several with interim data. What are your thoughts on interim data and immunotherapy? It seems to me that successful interim data could take many of these companies from $100 million market caps to $300 and $400 million market caps over the next year.
RJ - Your statement is true, but what I worry about with interim results in immunotherapy is progression. Dendreon had originally published progression-free survival, but what really worked for them was when they published overall survival. And the reason for that is because the immune system takes time to build, which is why you want to wait and see overall survival.
If I were advising an immunotherapy company, and some are doing this, I would use the interim analysis as just a suggestion for safety and not have an endpoint that is clinically relevant to the study. I fear interim analysis that has interim endpoints based on survival. I am skeptical with interim analysis in immunotherapy because you want to see overall survival, which takes longer to show up. Now, sometimes it can work. In the case of Galena, they really have a chance with that kind of peptide vaccine.
BN - So are you saying that interim analysis for immunotherapy products should be discarded?
RJ - My point was that immunotherapy takes longer to develop - just the nature of the immune system in recognizing an antigen or being modulated to respond. In many past cases, we used endpoints that were more relevant to chemotherapy of small molecule-targeted inhibitors of signaling pathways - i.e., FDA and clinicians had not moved with innovation in immunology in understanding that immunotherapy can't be evaluated with chemotherapy-like endpoints. So Dendreon had PFS or time to disease progression as its primary endpoint, with overall survival as its secondary endpoint. As you recall, the primary endpoint failed, but the gold standard of overall survival was reached.
Other points: Yervoy has a price tag of $120,000 and analysts predict peak sales of $1.4 billion for the product. Zelboraf, is the competitor of Yervoy; analysts predict peak sales of $730 million. Note that Cvac will cost much less.
Brainy
PRR Price at posting:
9.3¢ Sentiment: Buy Disclosure: Held
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