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  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    I hope you are right.
    Apr 13 09:58 AM | 3 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    A halt for efficacy would certainly be a shocker.
    Apr 13 09:54 AM | 1 Like Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    I make a lot of mistakes as does anyone dealing in the high risk biotech stocks that I am involved with. Look, BMY acquired Inhibitex for $2.75 billion to gain access to their hepatitis C drug. Nine months later they wrote off the entire investment because of a surprise toxicity issue. These things happen in the high risk world of drug development.

    Like DocLogic, I think that the role of the dendritic cell (Nobel prize for the discovery in 2011) can be more important than the checkpoint inhibitors. I have been involved with cancer vaccines for a decade and have seen all of them blowup with the exception of Provenge. I did not walk into the DVVAx-L situation with a happy smile and no understanding of the sad history of cancer vaccines.

    As for my integrity in writing articles, let me say this. I pride myself on presenting a balanced viewpoint in which I let people know the negatives and positives and what I know and don't know. I have never said that I am certain or can guarantee that DCVax-L will work. In my articles, I have addressed every issue (I think) that Adam has raised in a way that presents the negatives and positives of that issue. I think that my 2400 or so followers on Seeking Alpha and my website subscriber base means that readers also see it this way. I think that the issue with Adam is his balance and fairness. The issues are legitimate, but views on outcomes can be different.

    Some people say that my defense of NWBO is because I am pumping the stock. This is upsetting. What would be my motive? My website is a subscription based model. My only source of revenues is from my subscribers who beleive in my honesty and that I am working only for them. I am absolutely sure that I will make mistakes, and NWBO could be one. However, I think that all of my subscribers and all of my Seeking Alpha followers believe that I have carefully weighed the negatives and positives and made my best judgment. They trust that I have done in-depth research and sincerely beleive that there is a reasonable chance (not certainty) that I can be right. It is always a probability of outcomes, there is no certainty.
    Apr 12 05:33 PM | 2 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    It has been my suspicion that the delay in doing the efficacy analysis relates to resizing of the trial and not some problem with gathering data or some issue that the DMB has seen with the efficacy results. Here is my speculation. NWBO would have to get regulators in the US, UK and Germany to sign off even if the resizing is in the protocol and this can take time. Also, if the trial is resized, the new number of events needed to arrive at the first interim analysis should be larger and may not yet have been reached so that no efficacy analysis can or should be done. In this scenario, I think that the DMB would delay the efficacy analysis until all is finalized. My best guess is that the DMB hasn't even begun the efficacy analysis.

    I think that no DMB would decide to stop the trial for futility at this point. First of all, all patients are getting standard of care and there is no safety issue with DCVax-L. Second, we know that immunotherapy can be slow to take effect so that there might be no widening of the curves until later in the trial. Third, with the phase 1 results, only Adam would argue that the drug has no biological effect. The action by PEI strongly supports this line of thought. Even if the trial were in question of reaching its endpoint, there would be an incentive to see if they could determine a subgroup that might benefit.

    While Adam's argument that the trial is in trouble and could be stopped for futility now rules the field of thought, I think when we look back we will shake our heads as to why this happened. Also, we may conclude that the actions of management, which are not yet explained, increased the potential for the trial to be successful. What is troubling to me is that management has not been more transparent. This has allowed Adam to build up this strawman theory and then tear it down. I am frustrated.
    Apr 12 09:45 AM | 4 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    ICT-107 had the added problem that two different manufacturing sites and processes were used to produce cells for thier phase 2 and for phase 3 trials if they proceed they are using a third process. The FDA requires that manufacturers use and validate the same manufacturing process in clinical trials used to gain regulatory approval as will be used for commercialization. IMUC didn't meet this requirement while NWBO has achieved this in the US, Germany and UK. For that reason, I thought that even if the phase 2 trial were successful, IMUC would have to do a confirmatory trial. In all of these discussions on statistics and hypothetical trials outcomes, investors should not lose track of the essential fact that in cell therapy, the manufacturing process is the product. The acceptance of the manufacturing process in Germany and the UK is a significant accomplishment for NWBO.
    Apr 10 07:34 AM | 5 Likes Like |Link to Comment
  • Derma Sciences: A Not Well Followed Growth Company With Solutions For Diabetic Foot Ulcers [View article]
    Wound care is highly heterogeneous. Also, there has not been a lot of innovation so that many of the products have commodity characteristics. I think DSCI has done a very credible job in bringing differentiated products into their portfolio.
    Apr 5 10:17 PM | 1 Like Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    There has been a lot of discussion on this article and I personally have learned a great deal. None of us with the exception of Adam, knows how this drama will end. We each have taken a viewpoint based on our best judgment, but predicting the outcome of clinical trials is an art that requires the assessment of tens or hundreds or thousands of unconstrained variables. Hence, each of us should have considerable humility in our viewpoints.

    Sometimes, our discussions become so rigid and technical that we lose perception on what we are actually talking about. Let me try to approach the issue of progression free survival versus overall survival in a more human way. Let's first look at the importance of PFS versus OS in metastatic prostate cancer.

    Prostate cancer is a very slow growing cancer. If caught early before it escapes the prostate gland, it is curable by surgical removal of the prostate. If it has metasticized, because of the slow growth nature of the cancer patients can survive five, ten or twenty years. Metasticized prostate cancer patiens start treament with hormone therapies and the therapies progress on to Xtandi or Xytiga and then chemotherapy. If we look at hypothetical, somewhat typical patient put on treatment, progression might occur in months or a year or two years or more and the patient is likely to live three to ten years or much longer. I am making these numbers up, but they are still illustrative. In this situation, progression free survival is almost meaningless as an end point.

    Now let's take the case of glioblastoma multiforme. This tumor occurs in the tight space of the skull. It is a fast growing tumor that tends to have tentacles that spread away from the original tumor mass. If nothing is done, the tumor may expand rapidly and push the brain partially down the brainstem Even if the effect of the tumor is not that dramatic, it impinges on surrounding parts of the brain and can affect bodily functions controlled by that part of the brain with dire consequences. This is why once detected, the tumor is almost immediately resected whether it is in newly diagnosed or recurrent cancer.

    In the Stupp trial that defined standard of care in newly diagnsed glioblastoma multiforme, the progression free survival was 6.9 months and the overall survival was 14.6 months. The reason for this close correlation is that once the tumor starts to regrow the consequences are deadly. This is why key opinion leaders other than Adam place such importanceon progression free survival in GBM.

    In the two recent phase 3 trials newly diagnosed GBM, Avastin failed to reach statistical significance in overall survival, but some key opinion leaders argued that the improvement in quality of life by delaying tumor progression merited approval. In the case of recurrent glioblastoma, Avastin was approved without showing any improvement in overall survival.

    I don't know if the DCVax-L trial will show an improvement on progression free survival although I hope that it does. I also don't know that the FDA would approve it on this basis. However, in my weighing the evidence I conclude that there is a reasonable chance that it will hit the PFS endpoint and I think that there is reasonable basis for FDA approval if it does hit the endpoint. Reasonable and unreasonable men can disagree.
    Apr 5 04:16 PM | 7 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    It didn't hit the PFS endpoint.
    Apr 4 11:35 AM | Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    The FDA looks at the totality of the evidence. It all depends on the data. As I stated in the article PFS correlates with OS so I am not sure that you could have a dramatic effect in one and not the other.
    Apr 4 11:34 AM | 1 Like Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    The FDA does not allow companies to retrospectively change the primary endpoint of a trial. However, there was one exception and that was when Dendreon changed its primary endpoint for Provenge from progression free survival to overall survival.
    Apr 4 09:01 AM | 3 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    You are one of the few people on this message board who understands this. It is this point that P-man is missing in his analysis. It is why delaying the progression of the tumor in GBM is so important.
    Apr 4 04:39 AM | 8 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    If you did some work to understand the hospital exemption early access program, you would understand. From your comments, it is clear that you don't.
    Apr 4 04:24 AM | 2 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    Could you explain to me what you believe the German hospital exemption early access program is and don't say that it is named patient compassionate use, because it is certainly not. After we have come to an agreement on what this program is, could you explain the following regulatory action?


    The Paul Ehrlich Institute (the German equivalent of the FDA) has approved DCVax-L for all gliomas, not just glioblastoma multiforme. They obviously did not have overall survival data. What is it that PEI saw that caused them to take this regulatory action? If the PEI which is every bit as rigorous as the FDA in its regulatory action could do this, why could the FDA not take a similar course of action. I am curious to hear your reply but unless you can state what the German hospital exemption early access program is, it is pointless to go on with this dialogue.
    Apr 3 08:29 PM | 6 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    You are entitled to your opinion and could be right on PFS, but there are knowledgeable people who disagree. I provide a link to an article in Neuro-Oncology that states that PFS correlates with OS. I have also provided a link in which a key opinion leader discusses PFS as an endpoint. I would urge everyone to look at those two links.

    As a layman, I take their views seriously. Also some key opinion leaders argue that Avastin should be approved for newly diagnosed glioblastoma despite its not showing any improvement in overall survival in its phase 3 trials. Here is that link http://bit.ly/1dWetac

    Glioblastoma is a very rapidly growing tumor. It can actually push the brain down the brainstem and kill people in that way. That is why newly diagnosed GBM patients are quickly resected and why recurrent GBM patients are quickly resected.

    From my viewpoint and I am not alone, Improvement in PFS is a meaningful clinical outcome in GBM,
    Apr 3 06:32 PM | 6 Likes Like |Link to Comment
  • Refuting The Latest Negative Blog On Northwest Biotherapeutics [View article]
    Adam. I will not soon forget that you have said that I am pumping NWBO and being paid to do so. You seem to back off from that position with these moderate remarks, but my memory is long. Your sensationalist approach to journalism or whatever you call your job offends me. I try to present the positives and negatives as fairly as I can. I see none of that in your work. Your dismissal of the German hospital exemption early access program is an example of this. Your focus on the delay in the DMB delay in reporting efficacy results and implying that this signals problems with the phase 3 trial is also a canard.
    Apr 3 05:55 PM | 19 Likes Like |Link to Comment
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