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  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    I have also been puzzled by P-man. In some of his postings, he shows considerable expertise in statistical analysis and I have learned from him. However, the assertion that companies are as you so correctly put it "rifling through patient reports" and discerning information that allows a mid trial change in direction defies logic. No regulator would allow bias such as this to stand.
    Sep 2, 2014. 09:14 AM | 5 Likes Like |Link to Comment
  • Behind The Promotion Of Northwest Bio [View article]
    I asked Andrew Gengoes the question directly how many of the 154 patients screened but not randomized were excluded because of HLA status. Andrew would not give a number, but he said it was most of them. Of course what we are all trying to figure out is what is the addressable market for HLA-A2 patients. Here are my calculations.

    I am assuming that ICT-107, if successfully developed would be priced at $150,000 per treatment. Applying this price to a patient population of 1,200 to 1,800 patients in the US suggest an addressable market of $180 to $270 million in the US and an equivalent amount in Europe. Sales in the rest of the world are generally half that of the US and Europe or $90 to $135 million. Hence, I estimate that the worldwide addressable market for ICT-107 in newly diagnosed GBM patients with HLA-A2 immune status is $450 to $575 million. Let me explain how I arrive at these estimates.

    One of the enrollment criteria for participating in the phase 2 trials was that patients had to be HLA-A1 or HLA-A2 immune status. The Company screened 278 patients in order to find 124 patients who were randomized for the phase 2. The Company has not quantified how many of the 154 patients screened but not randomized were excluded because they were not HLA-A2 or HLA-A1 positive. It just said that “most” of the exclusions were due to this so I am left to define most.

    If all the exclusions were due to this immune status, it would mean that only 44% of the GBM population was HLA-A1 or A-2 positive. However, patients were excluded for other reasons so this seems too low. If we arbitrarily assume that a slight majority, then 51% of the 154 exclusions were due to immune status. With this assumption, then 72% all GBM patients would have positive HLA-A1 or HLA-A2 status. This seems too high. Let me arbitrarily pick a number that averages these two estimates and assume that about 57% of the GBM population has positive HLA-A1 or HLA-A2 status.

    In the phase 2 trial, 41% of the 124 randomized patients were A1 positive and A2 negative; 52% were A1 negative and A2 positive; and 7% were A1 positive and A2 positive. This indicates that 59% were A2 positive. If we take 59% of the 57% as previously estimated, this would suggest that 34% of the general GBM population would be A2 positive and eligible for enrollment in an HLA A-2 trial. Management has used suggested a higher number as it believes that 50% of the general population is HLA A-2 positive. I can’t explain the discrepancy.

    These tortured and I am sure difficult to follow estimations show that somewhere between 34% and 50% of newly diagnosed GBM patients are HLA-A2 positive patients who will be studied in the phase 3 trial. The National Cancer Institute estimates that there are 23,000 adults diagnosed with brain and other nervous system tumors each year. It further estimates that GBM accounts for about 15% of these cases or roughly 3500 are newly diagnosed GBM patients.

    Based on all of this, one can assume that ICT-107 will be initially targeted at 34% to 50% of 3500 newly diagnosed GBM patients each year in the US. This represents a population of 1,200 to 1800 patients each year in the US.

    But what about price? Breakthrough cancer therapies such as ICT-107 if successfully developed for small cancer populations suffering from life threatening cancers usually are priced at $100,000 or more per treatment. Indeed, Bristol-Myers Squibb’s new anti-PD-1 drug nivolumab was just approved in Japan (the first approval in the world) at a price of $145,000 per annual treatment.
    Aug 30, 2014. 10:48 AM | 3 Likes Like |Link to Comment
  • Behind The Scenes With Dream Team, CytRx And Galena [View article]
    I stand corrected on GALE. I see that the author was not short when he wrote those reports. From the tone of the reports I assumed they were sells. I guess my question is what was your recommendation on the March 13 report and what is it now?
    Aug 27, 2014. 05:33 PM | Likes Like |Link to Comment
  • Northwest Bio - You Can See This Data, But Not That Data [View article]
    I could see your point if n was going from 312 to 500 or 600. However, it is going from 312 to 348. Do you see any difference or do you consider any increase in n to be a signal that effect size is expected to be lower than originally thought.
    Aug 25, 2014. 12:06 PM | Likes Like |Link to Comment
  • Behind The Promotion Of Northwest Bio [View article]
    They won't publish it.
    Aug 24, 2014. 07:51 AM | Likes Like |Link to Comment
  • Behind The Scenes With Dream Team, CytRx And Galena [View article]
    Pearson gives us an "I told you so" statement in the beginning of this article and states that the stock traded at $8.00 at the height of what he speculates was a promotion of the stock. He proudly referred us to his article and pointed out that the stock now trades at $2.00. This leaves the clear impression that he called a move from $8.00 to $2.00. This is hardly the case. His article was published on March 13, 2014 when the stock was at $3.00. While this is a 33% decline in the stock this is about in line with what has occurred to a broad swath of emerging biotechnology companies since a serious correction began in March. He fails to mention this in his report. It appears that the correction in the stock is due to a sector decline rather than his article. In fact, Adam Feuerstein had made the same allegations nearly a month earlier when the stock was trading in the low $5.00. I think it is incumbent on an author to state price changes when he makes an "I told you so statement" as Pearson does in this article.
    Aug 23, 2014. 02:42 PM | 2 Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    PFS is extremely important in the case of GBM. This is a rapidly growing cancer that is confined to the skull. As it grows, it affects surrounding brain tissues leading to seizures and other severe side effects. It can actually push brain tissue into the brain stem. Preventing the progression of the disease can have an extremely positive effect on quality of life and hence a clinically meaningful benefit. I think that PFS is a solid endpoint in GBM. This is much less the case in some slower growing cancers such as early stage prostate or breast.

    While the shorts argue that this is a poorly designed trial, this is not the case. It is stratified for methylation status and there are statistical methodologies to determine the effect of risk factors such as age, degree of surgical resection, perfomance status and now the effect of white blood cell count at enrollment. This is the most important trial since Stupp in advanceing the understanding of GBM. I think that we will learn an enormous amount about sub-groups even if DCVax-L fails to reach its PFS endpoint for whatever reason.

    Let's hypothesize and that's all this is, an hypothesis, that the PFS endpont of 4.0 months is reached but OS is not statistically significant. Remember that patients on control are switched to DCVax-L if they progress so that this makes the OS comparison much more difficult. However, let's say that we see a strong trend in OS or statistical significance in one or more sub-groups. It makes it an easier decision for the FDA to approve DCVax-L.
    Aug 17, 2014. 11:17 AM | 5 Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    You are correct on Avastin; physicians don't want to put their patients on the drug. However, my comment was on Merck's and Bristol-Myers check point inhibitors, not Avastin. I was concerned that they would begin trials and attract most GBM patients making it difficult for ICT-107 to enroll patients in a new phase 3 trial. However, on its last conference call IMUC said that the checkpoint inhibitors are associated with troublesome CNS inflammation and that this would be a major deterrent to their use in a CNS tumor like GBM. I can't add anything beyond this at the present.
    Aug 15, 2014. 07:54 AM | 1 Like Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    You are right on Avastin; physicans don't like the drug. My concern was not with Avastin. I was concerned that Merck and Bristol-Myers would begin trials with their checkpoint inhibitors and this would make it f difficult to for ICT-107 to enroll patients. However, on the last conference call, IMUC went into great detail on this issue and maintained that concern about the propensity of checkpoint inhibitors to cause CNS inflammation, they may not be used in a CNS tumor like GBM. That is all I know.
    Aug 15, 2014. 07:49 AM | 2 Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    I have a hard time understandng what you are saying in light of what the chairman of the DMC said.

    “As the Company has stated clearly and specifically in its public announcements, the DMC has not conducted any efficacy analyses and the DMC has not provided any access for the Company to any clinical trial data. The DMC adheres to established clinical trial monitoring procedures and does not release any data while the trial is ongoing. This is an important issue, and it is surprising and troubling to see inaccurate claims being made by commentators who seem to lack a fundamental understanding of clinical trial monitoring. I have been on the DMCs for more than 60 clinical trials, and I have never experienced this type of attack.”
    Aug 14, 2014. 07:19 PM | 3 Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    The 55 raid progressors who did not qualify for the phase 3 trial were treated under compassionate use. NWBO picked up the cost. I don't think even AF can put a negative spin on this.
    Aug 14, 2014. 02:21 PM | 5 Likes Like |Link to Comment
  • Northwest Bio - You Can See This Data, But Not That Data [View article]
    For your information, the timing of an interim analysis is based on items written into the protocol, which in the case of the phase 3 trial of DCVax-L is a proscribed number of events, either death or disease progression. When the DMC is made aware by the CRO that this number of events has occurred, they conduct an interim analysis. NWBO has absolutely nothing to do with the timing of or performance or the analysis. They have absolutely no ability to control the timing or as you say push it back. You are badly mistaken on this issue.
    Aug 14, 2014. 12:40 PM | 4 Likes Like |Link to Comment
  • Behind The Promotion Of Northwest Bio [View article]
    I was amazed to hear P-man say that NWBO had seen clinical results from the phase 3 trial. He should know that this would unblind the trial and as a result, it could not be used for registration purposes. Virtually everyone knows that companies are blinded to clinical results until the completion of the trial. I am extremely surprised that he didn't understand that.
    Aug 14, 2014. 12:10 PM | 5 Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    Good point as usual.

    As an aside, Agenus is conducting a trial of Prophage in recurrent GBM. They are comparing Avastin plus Prophage to Avastin alone. They have stated in their conference calls that they are having trouble enrolling this trial because oncologists don't want to put their patients on Avastin.
    Aug 14, 2014. 12:04 PM | Likes Like |Link to Comment
  • Northwest Bio: The Data Monitoring Committee Addresses The Status Of The DCVax-L Trial [View article]
    Your point on PFS versus OS is well taken in the case of GBM. This is a rapidly growing tumor that is confined to the cranium. When it starts to grow it disrupts surrounding areas of the brain causing seizures and a whole host of side effects. It can ultimately push the brain into the brain stem. In GBM, progression free survival is an extremely meaningful clinical endpoint. Also, meta studies have shown that there is a very strong correlation between PFS improvement and OS improvement in GBM. This is well understood.
    Aug 14, 2014. 12:00 PM | 2 Likes Like |Link to Comment
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