Northwest: FDA hasn't agreed main endpoint for DCVax trial


The Street's Adam Feuerstein, who's having a bit of a running battle with Northwest Biotherapeutics (NWBO), digs deep into the company's 10-K annual report and finds that it hasn't agreed on a main target with the FDA for the Phase III trial of its brain-cancer vaccine DCVax.

Northwest wants the primary endpoint to be progression-free survival, but two other companies - ImmunoCellular Therapeutics and Celldex Therapeutics - have been using overall survival as the main goals of their trials for brain-cancer vaccines.

Northwest's shares are -3.1%.

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Comments (42)
  • alext1379
    , contributor
    Comments (811) | Send Message
     
    Progression-free survival sounds like its harder to achieve as overall survival seems to umbrella everything.

     

    If you can get progression free survival up, then it should mean overall survival would go up.

     

    I'm not a doctor though, I don't even have a Political Science piece of toilet paper degree.
    3 Apr 2014, 09:09 AM Reply Like
  • InmanRoshi
    , contributor
    Comments (217) | Send Message
     
    Especially since overall survival rate for glioblastoma multiforme is zero using current available methods, and average life expetency upon diagnosis is 14 months.
    3 Apr 2014, 11:22 AM Reply Like
  • iwasadiver1
    , contributor
    Comments (20) | Send Message
     
    I'm a physician, and progression free survival is considered an appropriate primary endpoint in diseases that are fast killers, like Glioblastomas. PFS is considered by most to be statistically close to overall survival in these instances because, as InmanRoshi states, overall life expectency is already very low.

     

    This Feuerstein character is a bit of a moron, but, as sensationalist reporting often goes he's doing his job well. He's turned a serious group of scientists and savy business persons into a bunch of idiots who don't know what they're doing. No true reporter of investment matters would be dishing out this kind of stuff if it wasn't for some other agenda, whether that's a mouthpiece for short sellers or simply to get people with conspiracy theory attitudes to subscribe to his blog.

     

    In any case, the science here is sound. I've been following NWBO for 4 years and starting investing after very careful research of their business model and research. The fact that they hung on for as long as they did without even remotely enough funding is a testament to their belief in their science and their product.
    10 Apr 2014, 12:34 PM Reply Like
  • Enlightened one
    , contributor
    Comments (16) | Send Message
     
    Why do you even repeat what AF says? Everyone knows he is bashing the stock to protect his shorts. Such BS!
    3 Apr 2014, 09:13 AM Reply Like
  • rz60
    , contributor
    Comments (27) | Send Message
     
    Sounds like a "standard disclaimer" that should be in a 10-K. There are no guarantees at this point otherwise NWBO would be sitting at $300 right now.
    3 Apr 2014, 09:37 AM Reply Like
  • Relayer
    , contributor
    Comments (38) | Send Message
     
    Correct, a disclaimer... one that was present in November of 2013. More AF non-news.
    3 Apr 2014, 01:27 PM Reply Like
  • capcod3
    , contributor
    Comments (9) | Send Message
     
    See 2007 NWBO kerfuffle over Swiss "fantastic results" that were based on only a few patients. Stock went up like crazy and then collapsed. Lawsuits followed. AF justified in being negative about NWBO. Management there kind of shady.
    3 Apr 2014, 09:45 AM Reply Like
  • alext1379
    , contributor
    Comments (811) | Send Message
     
    AF will be negative on whatever he's paid to be negative on.

     

    Hell, he'll be negative on Aspirin if you pay him to write it.
    3 Apr 2014, 09:51 AM Reply Like
  • Relayer
    , contributor
    Comments (38) | Send Message
     
    I seriously doubt that he's on anyone's payroll or has any financial interest here, that would be too easy to track and get caught doing. His persistent (bordering on psychotic) hammering of this company looks and smells like a personal grudge. Funny, he wrote another "article" today looking at opportunities in the biotech sector. He failed to mention the fortunes to be made shorting NWBO. ;)
    3 Apr 2014, 01:43 PM Reply Like
  • tinsley09
    , contributor
    Comments (339) | Send Message
     
    It is disappointing to see that this cite is attempting to rescue the rapidly ERODING credibility of A.F.by dredging up technical issues(p.f.s. vs o.s.) that are beyond the comprehension of most readers on this page.So much for the recent accolades earned in academic journals empirical analysis of "Wisdom of the masses" vs expert opinion..Simple manipulation by S.A. of the triggers(H.P.A.A.) of human doubt and fear.
    3 Apr 2014, 09:55 AM Reply Like
  • longimgn
    , contributor
    Comments (852) | Send Message
     
    WOW........AF has a large following and his comments seem to move market pps..
    That he spends this much time and effort on little NWBO means that he sees great value in the company....right now, he proclaims negative value, but, if it proves to work, then it will have great positive value...I love it that he brings such
    awareness to the masses of what NWBO is attempting to do......Come on, AF has made this a Broadway production.......He pans it without even seeing the show, but, the public interest grows everyday....Can't wait to see the opening when the curtain goes up......some show, getting ready for biggest hit in town......cheers
    and good luck longs
    3 Apr 2014, 10:07 AM Reply Like
  • tinsley09
    , contributor
    Comments (339) | Send Message
     
    This report by S.A to prop up A.F.rapidly exploding credibility , is ANOTHER disappointing CYNICAL effort , that follows up their prior decision to equate Linda Powers address to the New York Academy of Medicine( New York Academy of Sciences) with the distortions published in Cramers rag.I was hoping that the recognition by the academic community of S.A.contribution to the" expert opinion vs wisdom of the crowd"statistical debate,would inspire them to ELEVATE their EDITORIAL standards along the lines proposed by empirical studies of human 1)decision making and 2) credibility by Nobel Prize winning (in Economics) by psychologists like the late Herbert Simon of Carnige Mellon and Daniel Kahneman and Amos Tversky of Stanford University.There are enough rags out there contributing to the" signal to noise ratio' in economics.I was hoping that Seeking Alpha would be inspired by academic recognition to elevate the pedestrian debate out of the MUD.

     

    CA
    3 Apr 2014, 10:53 AM Reply Like
  • scrxd again
    , contributor
    Comments (20) | Send Message
     
    I wouldn't wish GBM on anyone (almost), but I am curious which trial Af would want to get into if he or one of his was diagnosed. Maybe one with two patients already passing the 10 year survival mark? Oh, that would be DCVAX-L.
    3 Apr 2014, 11:35 AM Reply Like
  • libouban
    , contributor
    Comments (142) | Send Message
     
    ASCO (top oncology conference) & MD Anderson (top cancer center/research) on one side. AF on the opposite. Who do you trust?
    3 Apr 2014, 12:57 PM Reply Like
  • tinsley09
    , contributor
    Comments (339) | Send Message
     
    You can see TODAY(4/3/2014) in REAL TIME the immediate impact on NWBO's price of DISTORTED headlines which are" FALSE and MISLEADING"( Linda Powers). There is a massive subset of NWBO investors who have no INTELLECTUAL IMMUNITY to A.F. distortions. Their vulnerability on technical issues in clinical oncology(P.F.S. vs O.S. )plus in science and statistics is driven by their innocence of science and statistics. They are easily driven to panic by FALSE and MISLEADING HEADlines.Multiple converging complaints NOW, to the SEC may have some efficacy in blunting the PREDICTABLE distortion of the even MORE technical report by Vivek Subbiah et al (MD Anderson Cancer Center) in May 2014.
    3 Apr 2014, 01:35 PM Reply Like
  • BILLYJIMBOB1
    , contributor
    Comments (50) | Send Message
     
    Got to say AF is stretching here , Why is progression free survival a bad outcome as compared to Death.... What a hack I think that NWBO will possibly chase AF due to his continual attacks against the company ....
    3 Apr 2014, 12:58 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    Funny how so many people don't understand the difference between PFS and OS, yet the invest in biotechs and defend them religiously.

     

    To date, the FDA has preferred OS as a primary endpoint over PFS. Any company using PFS as a primary endpoint is doing so at risk.

     

    It really comes down to that.
    3 Apr 2014, 01:17 PM Reply Like
  • alext1379
    , contributor
    Comments (811) | Send Message
     
    PFS means the cancer has been halted no? OS means you're alive but still sick and cancer may still be progressing but at a slower rate.

     

    If you can hit PFS, you can hit OS.

     

    Just like AF tried to tell us having a P value of 0.02 is bad because P value of 0.05 is easier to hit. If you can hit 0.02, you can hit 0.05. Even if you miss 0.02 you're more than likely still going to get 0.05.

     

    AF is trying to fool stupid people and/or trigger computer trades with keywords in his titles.
    3 Apr 2014, 02:25 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    In this case, NWBO have a crossover arm that gives access all patients who progress access to DCvax (Both placebo and treatment arms).
    This muddies OS as a primary endpoint, hence PFS being selected as the primary.
    3 Apr 2014, 03:24 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    Essentially, PFS rates the size of the tumor. It the tumor has grown by 20% or more, the patient is considered to have 'progressed'. Of course, you can still be alive and be 'progressed'.

     

    OS quite simply measures death. And you can die while not being 'progressed', although normally pts die after progressing.

     

    There is a lot of debate in the scientific community as to whether there is a correlation between PFS and OS. Intuitively it seems to make sense that as PFS expands, OS should expand. However, the data so far has been conflicting. It's possible that pts with increasing PFS are still dying more or less at the same time than those that do not have increasing PFS. And if that's the case, then PFS really doesn't matter if the only thing you care about is staying alive.

     

    The argument to that is that even if pts still die at the same time, the burden of the disease eases with expanded PFS. A tumor not growing presumes less complications and symptoms. So if you only have a year to live, and there's not much you can do about it, would having less burden during that year be a benefit? If you are that patient, the answer is most likely yes, but from a regulatory perspective, is that benefit worth approving a very expensive drug that doesn't increase your life expectancy?

     

    As of now, the FDA seems to side with 'no' to that last question, although it is an ever-changing landscape.
    3 Apr 2014, 03:47 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    There's a strong correlation between PFS and OS in GBM:

     

    http://bit.ly/OfLUbN
    3 Apr 2014, 04:14 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    You mean "It is the opinion of these researchers that there is a strong correlation between PFS and OS in GBM".

     

    For every study 'proving' one thing, there likely is another study showing the opposite. The criticism of the study you cited is that there are flaws in how the data was obtained.

     

    I'm not saying I disagree with the finding, just that this data has been debated.
    3 Apr 2014, 04:26 PM Reply Like
  • longimgn
    , contributor
    Comments (852) | Send Message
     
    P Man.....I have followed your comments and discussions about P values and you seem to me to know much more about it than certainly me and many other investors or commentators.....That said, would you please
    go today's rebuttal by Smith on Stocks to the opinions about PFS as a legitimate endpoint for GMS.......He explained it in his way and I would like to see you answer him with your knowledge about trials and what are the strongest endpoints......Someday, the FDA will answer all of us with its decisions about D "L".....till then, we just give our opinions, or like me,
    just listen and hope that the treatment is approved because, if it is approved it is the most humane and effective treatment available......That's certainly something to hope for...But, hope should be informed by facts, and that is where all this discussion comes in.......Thank you for adding to it........cheers, long
    3 Apr 2014, 04:41 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    I already have commented there.

     

    Since we do not know if this drug works, we shouldn't "wish" it to be approved. We should, I guess, wish that it works. If it works, it'll be approved.
    3 Apr 2014, 05:17 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    No, not their opinion. Their findings. Based on the data.
    Of the total published GBM trials (274), 91 had sufficient PFS and OS data:

     

    "Published glioblastoma trials reporting OS and ORR and/or PFS with sufficient detail were included in correlative analyses using weighted linear regression."

     

    It may have been an opinion before their study, but it's now published.
    3 Apr 2014, 05:20 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    Whoops, meant to rely to your comment above.
    Also, perhaps you were referring to their conclusion being opinion, in which case, yes. That would be considered opinion. Not the correlation.
    3 Apr 2014, 05:24 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    You can look at any medical issue being researched and find papers arguing one side of it and also find papers arguing the other side of it. Being 'published' just means the peer reviewers found the methods and conclusions credible; it does not mean they agree with it.

     

    All data can also be interpreted in many ways, too. Thus, "based on their review of the data, the team concluded that...." is a better way to say it.

     

    It is also better to say that "there is a growing body of evidence suggesting a correlation between OS and PFS; however, to date, the FDA has not accepted PFS as a surrogate endpoint for a registration trial for newly found GBM".
    3 Apr 2014, 05:41 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    We're descending into the mire of semantics, but my issue with your post was stating their findings were an 'opinion'.

     

    From all studies to date (where PFS and OS were sufficiently measured) there is a strong correlation. This is from all the available data, not a selection of it.
    To say that their findings are an opinion severely minimises the weight of the evidence.
    Their conclusion stating "PFS may be an appropriate surrogate for OS" is an opinion. One based their findings (strong correlation) which is fact.
    3 Apr 2014, 05:50 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    Findings that were based on data mining. Which should always be taken with a grain of salt.
    3 Apr 2014, 05:56 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    I don't agree that it's data mining. Sure, the individual trials may not have been set up to demonstrate a PFS-OS correlation but this is meta-data analysis, not mining one trial.
    Since the study was set up to find out if PFS could be used as a surrogate endpoint on trials, trials are the perfect examples to study for the data.
    It seems you're being vehemently contrary, any reason?
    3 Apr 2014, 06:54 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    I could switch it around and say you're being vehemently contrary. I stated that the data as to whether there is a correlation between PFS and OS debatable, and yet you are confronting every statement I make. Any reason?
    3 Apr 2014, 07:08 PM Reply Like
  • longimgn
    , contributor
    Comments (852) | Send Message
     
    Yes P Man and thank you for making that important distinction......If it works, it will be approved and the world will be a better place because people with cancer will have a better option than they have right now with Chemo, Radiation or surgery....I sure hope the real #'s come out sometime
    soon and you can digest them and report on their meaning and what the odds might be that the FDA might approve this type of treatment for the indication that it was designed to demonstrate better results than SOC....
    Thank you for taking your time and energy and knowledge to help people
    like me to know more and speak better about what is really new for me....cheers, long
    4 Apr 2014, 05:20 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    Their current study will provide both OS and PFS data. If they hit on OS, it's almost a no-brainer that they'll get approval. If they hit only on PFS but not OS, it's a tough call.
    4 Apr 2014, 05:34 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    Fair enough, though I've been defending data, you've been calling it opinion.

     

    The data isn't debatable, that's my whole point.
    Where's the debate?
    Is there more trial data available to them that they didn't study? No.
    Are their findings based on the evidence presented? Yes.
    Was there a strong correlation demonstrated in the data? Yes.

     

    The only debate I can see is their conclusion that suggests PFS could be used as a surrogate endpoint. It's a valid conclusion, and quite possibly correct, but it relies on a number of assumptions.

     

    Or do you have issue with the data?
    4 Apr 2014, 09:45 PM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    The study that I looked at (not sure if it's the same one) only looked at data less than 12 months, which concluded that there possibly is a relationship between PFS and OS. However, it did not look at data beyond 12 months. So, the data itself did not lie, but it was a subjective cut of data that was selected to look at in the first place.

     

    So, you always have to be careful when quoting data because although the data itself may not 'lie', the lie could have been in choosing which data to look at.

     

    The bottom line, though, is that it really doesn't matter if it's a surrogate or not; the study NWBO is running now will produce both results. So if PFS is positive but OS is negative, it's obviously not a surrogate. And probably not approved.
    4 Apr 2014, 11:24 PM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    Yes, that's true (bottom line). But the post-progression crossover arm complicates the OS data.

     

    For what it's worth, here's an article that was posted elsewhere that refers to FDA's position on PFS. Specifically in response to AF's latest diversion.

     

    http://bit.ly/1jdHJsi
    5 Apr 2014, 12:16 AM Reply Like
  • P Man
    , contributor
    Comments (1494) | Send Message
     
    I agree 100% about the problems with the crossover design and OS. It doesn't seem fair to be forced to use an endpoint that essentially, in theory, will have both study groups receiving treatment. You make your study drug have to beat....your study drug.

     

    One could argue that the survival rate of someone with RECURRENT GBM (as one would likely state this is) who is not being resected is not very good, and that the data will bear that out with OS. Personally I don't know enough about it to state firmly one way or the other.

     

    However, the guidance does state that if you want to use PFS for your endpoint, you need an SPA in place designating it as such. The FDA in this case may not bind themselves to that guidance and might approve a drug based solely on PFS.

     

    My whole point is that this is a risk - be it small, or large. A study that used OS - or had an SPA in place stating PFS was OK - would be far more calming, in my opinion.
    5 Apr 2014, 12:39 AM Reply Like
  • f3tt
    , contributor
    Comments (96) | Send Message
     
    Agreed.
    They never got the chance for the post-P2 SPA due to the P3 upgrade, so we're a little off-piste.
    I'm quite confident that if there is a meaningful PFS benefit the FDA would approve it. But as you say, it would be nice to not have any risk.
    5 Apr 2014, 01:37 AM Reply Like
  • Relayer
    , contributor
    Comments (38) | Send Message
     
    AF has a personal vendetta against NWBO, clearly. He relies on the shock value of misleading headlines and (as another poster suggested) technical jargon that the average investor won't understand anyway. Cheap shots and reprehensible.
    3 Apr 2014, 01:32 PM Reply Like
  • longimgn
    , contributor
    Comments (852) | Send Message
     
    Thank you P Man.......good insights to how these statistics are evaluated and the many considerations that go into determining what is the best treatment available...Guess you know that NWBO seems to be saying that its treatment plan is not soooo expensive?? It is taken once, manipulated, frozen and available
    for 3 years, if needed........no more cost......If it is approved and available, it seems like it will also bring down the cost of treatments.....Big Pharma will be in knots because their treatments are very costly and must done on a regular basis....jMHO.......ch... and thanks
    3 Apr 2014, 04:49 PM Reply Like
  • Onwards and upwards
    , contributor
    Comments (4) | Send Message
     
    Not exactly: the correlation between PFS and OS is highly variable - it is possible to see an increase in PFS and no effect on OS for example. The strength of correlation depends in part on tumor type and tumor stage. Also,in general, the smaller the difference between PFS and OS, the stronger the correlation between the two.
    3 Apr 2014, 07:05 PM Reply Like
  • William Peters
    , contributor
    Comments (15) | Send Message
     
    alext1379 you are right on the money; the primary endpoint of PFS is sound as a pound
    3 Apr 2014, 07:18 PM Reply Like
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