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  1. [verwijderd] 27 november 2006 13:25
    By: rancherho Send PM Profile Ignore Recommend Add To Favorites
    Posted as a reply to msg 17223 by walkinizer

    Re: Provenge, Chemos and FDA Approval
    1. >>The all cause mortality analysis was separate than the original 9901 survival analysis, if that was your point?, but in both cases the high survival group was provenge followed by taxotere, so whats your point here? <<
    The data that Dr. Small presented on 9901 including post Provenge chemo use establishes a benefit for Provenge montherapy, as well as a potentially greater synergistic survival benefit with docetaxel (Taxotere), Dr. Petrylak uses integrated 9901/9902a data; no 9902a only docetaxel data was given. His data supports a synergistic effect for Provenge and docetaxel, but without more specific 9902a data does not disprove benefit from Provenge alone for those who choose not to take docetaxel.

    2, >>The CD54 survival correlation data is encouraging and exciting, but at this point is coincidental. There is no mechanism of action which explains the data. << CD54 antigen presenting cells matured fron peripheral blood monocytes
    preferentially prime memory T cells and are not preferentially "homed" to skin as many skin dendritic cells recruited at injection sites for other therapeutic vaccines may be. In addition to independent studies supporting these hypotheses, the long term T cell proliferation data reported in P11 is undoubtedly generated by memory T cells rather than short lived effector CD8 T cells.

    3.>>The median survival of the placebo only group was about 15 months and the provenge only group 19-20 months, plenty of time to go on taxotere treatment if they chose to due so. No selection bias going on here imo.<< Forget selection bias for now, the 36 month survival rate of the 9901 Provenge only group was higher than the placebo + Taxotere group, though not as high as the rate for the Provenge plus docetaxel group. In the Taxotere only trials, the cytotoxic effect of Taxotere diminished over time post the 7 month max course of therapy as the surviving cancer cells developed drug resisitance and resumed growth. Chemo does not have "memory" since accumulation in a patient would violate ADME (absorption, distribution, metabolism and excretion) standards and likley kill more patients than it already indirectly does. As the P11 data demonstrates the Provenge primed immunity attack has memory.

    4.>>Have you seperated out the chemo 2nd line benefit from monotherapy? <<
    Taxotere acts synergistically with other experimental prostate cancer vaccines, though increasing median survival for a shorter period with the discontinued Therion vaccine and only in mouse studies for CEGE's GVAX vaccine. See: (a) A Randomized Phase II Study of Concurrent Docetaxel Plus Vaccine Versus Vaccine Alone in Metastatic Androgen-Independent Prostate Cancer Clinical Cancer Research Vol. 12, 1260-1269, February 2006 clincancerres.aacrjournals.org/cgi/co... (b) www.biospace.com/news_story.aspx?Stor...
    One of the invited speakers at the FDA/NCI workshop on therapeutic cancer vaccines on 2/8 - 2.9/07 is Eliabeth Jaffee of John Hopkins, a co author of: Review Article: Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy Leisha A. Emens1 and Elizabeth M. Jaffee1,2,3,4 Departments of 1 Oncology, 2 Immunology, 3 Pathology, and 4 Pharmacology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland Cancer Research 65, 8059-8064, September 15, 2005 cancerres.aacrjournals.org/cgi/conten...
    I seriously doubt whether Drs. Petrylak or Jaffee, or any FDA doc, including Dr. von Eschenbach, would seriosly contemplate denying FDA approval to a new therapy, if in fact, its efficacy can be further improved to levels never seen in AIPC before by combining it with a later chemo or other adjuvant.

    5.>>Therefore, that which is perveived to be the most important variable should be the one given first, and that is Provenge. <<
    I agree with that statement, but it is a jump of faith and not even close to being proven.<< Logic does suggest that a therapy with low side effects with a durable long term effect against AIPC would be far more acceptable to many asymptomatic AIPC patients who may remain undecided about taking a chemo, expecially where other studies have shown that high levels of PAP, the Provenge antigen target, are associated with increased bone mets. The Therion vaccine also showed some synergistic effects when docetaxel was given after not before the vaccine. Dr. Jaffee's Review descibes some developing principles on what may be an optimized sequence for benefit.

    6. Perhaps you should also familiarize yourself with Dr. von Eschenbach's opening comments at the 9/2005 2 day NCI Immunology Symposium, where any doubts that appropriate adoptive cell therapy in cancer can work was being dispelled by the work of Drs. Rosenberg and Restifo, who are also presenting at the 2/8 - 2/9/07 FDA / NCI workshop. Provenge is, of course, an adoptive cell therapy as well as a therapeutic cancer vaccine. Dr. Provost will be presenting updated Provenge CD54 Upregulation data at the FDA/NCI workshop. There is little question that some control of the immunosuppressive effects of Tregs and better understanding of antigen cascade / antigen escape with regard to therapeutic cancer vaccines may open options to further increase efficacy. However, the FDA's recent action in approving Gemzar as a late stage salvage therapy in ovarian cancer on the basis of overseas trials where the FDA was not involved, where PFS was increased, but overall survival was reduced, and where ODAC recommended disapproval, reportedly in order to give a patient's oncologists more therapy choices, together with von Eschenbach's strong support of immunological therapies in cancer should give no comfort to those believing that the present FDA will await therapies even more improved while patients die, rather than get the best to patients now and continue researching better single and combined therapies. All JMHO.

    Good luck to all DNDN longs.



  2. [verwijderd] 27 november 2006 18:05
    quote:

    crackedtooth schreef:

    heb op 4,25 bijgekocht vandaag oa ivm lazard presentatie van DNDN morgen

    S1 4,25/426
    S2 4,11
    S3 4,01
    zit nu echt zwaar te twijfelen, heb 2,5 k op5,34 daarna 7,5 k op 4,66 en 5k op 4,61 , allemaal verkocht op4,54 verwachtte toch verdere daling...... ivm met de genadeloze shorts maar hier zou toch wel eens de bodem kunnen zijn....... ga denk ik toch nog ff wachten....als ie vertrekt dan heb ik pech gehad...koop ik hoger bij... alles onder de 5 is toch redelijk goedkoop , wacht eigenlijk ENCY een beetje af , indien die goedkeuring krijgen dan is het risico eraf, kan ik wat groter in DNDN, toch erg veel geloof in wat het spul doet....
  3. [verwijderd] 27 november 2006 21:41
    heb er toch maar 5k van gekocht op4,23...kon het niet uitstaan geen aandelen te hebben als ie vertrekt..... deze verkoop ik niet....ga er echt mee in de wacht, hoewel ik verwacht dat ie best nog wel eens lager zou kunnen worden gezet.....
  4. [verwijderd] 27 november 2006 21:58
    quote:

    leguaan3 schreef:

    heb er toch maar 5k van gekocht op4,23...kon het niet uitstaan geen aandelen te hebben als ie vertrekt.....

    [quote=SkySpam1]

    jij koopt ???
    je werkelijk GEK !!
    in de letterlijke zin vh woord !!

    leg koopt en koopt en koopt en koopt en .............???

    [/quote]
    [/quote]
    [quote=gideon1404]

    Wat is die Legi voor een maloot. Legi doet dit en Legi doet dat. Het lijkt er me er een van de Josti-band
    die een klasje is begonnen.
  5. [verwijderd] 27 november 2006 22:18
    quote:

    SkySpam1 schreef:

    [quote=leguaan3]

    heb er toch maar 5k van gekocht op4,23...kon het niet uitstaan geen aandelen te hebben als ie vertrekt.....

    [quote=SkySpam1]

    jij koopt ???
    je werkelijk GEK !!
    in de letterlijke zin vh woord !!

    leg koopt en koopt en koopt en koopt en .............???

    [/quote]
    [/quote]
    [quote=gideon1404]

    Wat is die Legi voor een maloot. Legi doet dit en Legi doet dat. Het lijkt er me er een van de Josti-band
    die een klasje is begonnen.
    [/quote]

    Nee hoor gewoon kopen...dus order trade box gaat heel snel.... order valideren en klaar is kees...DNDN is nm heel goedkoop aan het worden zoals gezegd...... INSM is een hold, ENCY een buy...wilde 120k hebben en die heb ik nu binnen , nu is het wachten of groot de boot in of groot verdienen.....en DNDN...Tja die koop ik nu voor 2009!! hehehe
  6. [verwijderd] 4 december 2006 21:00
    quote:

    leguaan3 schreef:

    ?????? gaan de shorts weer lekker doen?????? zie op trade box de getalletjes heel snel naar boven........hehehe
    Ja Koala, wellicht zit ik toch goed met mijn 20K gokje.
    En nu Ency nog.

    Psycho
    ++ 5%
  7. [verwijderd] 5 december 2006 13:35
    CNBC PFE video
    www.cnbc.com/id/15840232?video=150398297

    the section where DNDN is mentioned by Duncan starts at about the 4:40 mark into a 7:47 presentation on PFE. Listen to the whole video if you're looking for info on PFE as well.

    (los ervan pfe ceo www.cnbc.com/id/16038143 )
  8. [verwijderd] 5 december 2006 16:27
    quote:

    DieGroeneGigant schreef:

    Inderdaad DNDN wordt uitgebreid besproken. Bedankt voor de link.

    print.chartnet.nl/Show.cgi?Img=609769...

    Voorlopig genoeg ruimte naar boven (naar 5.50)
    en los van TA verwacht ik tussen 20dec en half januari bericht van priority review FDA
    klinisch deel 1+2 gefiled eind aug 2006
    Cmc gedeelte (productie) gefiled in nov
    dus BLA is klaar
  9. [verwijderd] 10 december 2006 22:48
    Nu Genmab wel nog een stuk door zal lopen, maar Medarex binnenkort toch wat stoom verwacht wordt af te blazen na die eveneens verrukkelijke stijging wordt het nu weer tijd aan Dendreon te gaan denken.
    Een erg goed stuk informatie uit -investorvillage -van 10 december.
    www1.investorvillage.com/smbd.asp?mb=...

    Om je vingers bij af te likken.
    groet
    leo s
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