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OXiGENE, Inc. Message Board

shiteferbrains 46 posts  |  Last Activity: Oct 12, 2014 3:08 PM Member since: Jan 30, 2014
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  • shiteferbrains shiteferbrains Oct 12, 2014 3:08 PM Flag

    Regardless of the past performance of OXGN sp the GOG 1861 data shows that Avastin/Zybrestat combo produces an extended PFS benefit in recurrent ovarian cancer. Will there be any OS data released/updated in November? Unknown. If you are Roche though, you've got to be thinking that Fosbretabulin/Z might be a great combo drug for Avastin, and that the cost of buying up Oxigene at a reasonable premium to the current sp (so that with their huge cash reserves they could bring it through approval that much sooner) would be a no brainer for them. Fosbretabulin would add value to the Avastin franchise. It's really that simple.

  • Fear monger the heck of it!

  • The 24/7 basher urging everyone to sell is gone for the moment and instead there are the replacement aliases warning of impending doom coupled with a low volume takedown in a small cap nightmare of a market. Put your heads together and come up with a better way to spin it because your use of the Yahoo message board as a co conspirator is lame at best. Stop the fitzing around already, and like I've said before, use that juice you think you "all" have and make the sp really tank to under two dollars! C'mon Henny Penny, let the sky fall already.

  • shiteferbrains shiteferbrains Oct 6, 2014 7:48 PM Flag

    These two prior Avastin P2s in recurrent ovarian cancer were only single agent Avastin trials I could find to compare what Z/A results might come in as. Patient population is always different of course, as seen in the 2nd trial's 90% platinum resistant and the first having 'only" 58%. Look at the OS difference between the two; +6 months for the first trial with the lower platinum resistant group.

  • Avastin gained EU approval in Europe on the results of AURELIA trial median PFS of 6.7 months for Avastin/chemo combo results, but GOG trial 1861 combo arm of Zybrestat / Avastin had a stat significant median PFS of 7.3 months. Comparison of results show that Avastin/chemo results are inferior to Avastin/Zybrestat results in recurrent platinum resistant ovarian cancer. A phase three trial of Zybrestat / Avastin, if it were to match GOG 1861 results would then qualify the combo usage of these two drugs for approval in at least the EU.

  • shiteferbrains shiteferbrains Oct 3, 2014 2:54 PM Flag

    OS was not stat sig. Allowed for crossover upon progression of disease. Was not primary endpoint.

  • shiteferbrains shiteferbrains Oct 3, 2014 2:32 PM Flag

    GOG Trial 1861 Z/Avastin stat sig primary endpoint PFS of 7.3 months beats AURELIA Trial Avastin/chemo primary endpoint PFS result of 6.7 months.

  • {{ Women with recurrent, platinum-resistant ovarian cancer who received Avastin in combination with chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) had a median progression free survival of 6.7 months compared to 3.4 months in women who received chemotherapy alone.

    That's from Roche's own release

  • But Roche didn't, did they? Bevacizumab / Avastin is already used off label for this cancer because of the PFS benefit it provides to many women in this very high mortality disease. Zybrestat combined with Avastin in this group resulted in a stat sig PFS result vs Avastin alone. That's nothing? This is coming from a liar that posts references to "articles" here that are really no more than opinion pieces from other message boards. Platinum resistant ovarian cancer is deadly, and there is no hope for these women once the cancer is recurrent. Is the hypertension in the dual usage arm of GOG 1861 treatable? The abstract does not provide details. Is there any OS benefit in the combo arm? The abstract does not give any hint. The PFS results are the results. Stat significant PFS is stat significant PFS. The 24/7 basher (700 posts here last three months alone) that haunts the OXGN Yahoo message board is here to spread a negative spin on everything having to do with this stock, nothing more.

  • shiteferbrains shiteferbrains Oct 3, 2014 10:14 AM Flag

    pharma, I am all for the non-toxic effect, but also, I'm thinking that Roche, who doesn't hesitate to test Avastin in chemo combo trials, would want to use the stat sig PFS benefit of Z/Avastin combo in Z/Avastin/chemo combo trials to push the envelope in trying to reach stat OS in indications where Avastin/chemo have not, regardless if by crossover contamination.

  • shiteferbrains shiteferbrains Oct 1, 2014 2:01 PM Flag

    So the cancer cells not killed by the initial hypoxia (oxygen deprivation) brought on by Z/Avastin become susceptible to death by necrosis (without blood supply they are in a nutrient devoid environment) and can even activate an immune response to help through the inflammation caused by the necrosis. ????

  • I've posted before that ovarian cancer cells are are glycolytic as compared to normal, untransformed cells, and are sensitive to glucose deprivation, and that glucose molecules are delivered to cells by the circulating blood. When the Z/Avastin combo is delivered, by design the existing vasculature is destroyed by Z and any new vasculature will be prevented by Avastin. This glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells. OK, so here's another possibility as to why the Z/Avastin combo might work so well as a team in this indication:

    {{ Early studies of the metabolism of cancer cells had indicated that cancer cells rely preferentially on glycolosis for ATP production, a phenomenon initially called the Warburg effect ...
    {{ The minute a cell that is dependent on glycolysis consumes all of its cytoplasmic NAD, it can no longer produce ATP,” Thompson stated, “and it has to die.”

    Now, this next passage is in the context of a chemo reaction:

    {{ “When cells die apoptotically,” Thompson noted, however, “they specifically block immune responses. In contrast, necrotic cell death is very proinflammatory.” So when cancer cells die from necrosis in response to the chemotherapy, this would activate the innate immune response and possibly, if there are cancer-specific antigens, activate a response against the remaining cancer cells, providing a potential way for the immune system to actively deal with the remaining cancer cells.

    But oxygen/nutrient deprivation (Z/Avastin combo) to ovarian cancer cells also leads to apoptosis thru Hypoxia and necrosis:
    {{ Apoptosis can be induced in response to hypoxia. The severity of hypoxia determines whether cells become apoptotic or adapt to hypoxia and survive. A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic.

    continue into next post.

  • shiteferbrains shiteferbrains Sep 28, 2014 1:50 PM Flag

    {{ Researchers had previously reported the Perjeta drug regimen significantly extended progression-free survival, or the period of time patients live without their disease worsening, but the final overall survival data has taken longer to collect.

    Hmmm, didn't the Zybrestat/Avastin combo arm of GOG 1861 significantly extend PFS?

  • [[ The result is a vindication of combining medicines that fight tumor cells in a variety of ways.

    One would think that Roche might then be fairly interested in the extended PFS Zybrestat/Avastin combo results from GOG 1861, especially when they could make it their own in a blink...

  • November 19th is the PDUFA date for Avastin's AURELIA trial. A positive decision will put to bed the notion that stat sig PFS results are not good enough to gain FDA approval in ovarian cancer.

    Approval for Avastin based on its positive PFS results in AURELIA will effect the valuation being given for the GOG 1861 stat sig results for PFS in the Zybrestat/Avastin arm, IMO.

  • A piece of the puzzle for statistical significant PFS results of GOG 1861? Does Oxigene's VDA work better in a soft tissue environment for destroying existing tumor vasculature?

    [ Ovarian cancer cells spread, or metastasize, by a different method than other cancer cells. Breast cancer cells, for example, break off from a solid tumor and flow through the blood until they arrest in small blood vessels. The cancer cells then penetrate the vessel surface to form a tumor. Because ovarian tumors are in the abdomen, these cancer cells are shed into the surrounding fluid and not distributed through the blood. They must be able to adhere directly to the fatty tissue that lines the gut, called the omentum, to begin forming a tumor. The new study discovered details about how ovarian cancer cells seem to prefer the mechanical properties of this soft tissue.

  • Reply to

    Chemo plus Avastin Numbers

    by bullahoop Sep 21, 2014 9:52 PM
    shiteferbrains shiteferbrains Sep 22, 2014 11:53 AM Flag

    *The FDA has assigned a priority review designation to bevacizumab (Avastin) in combination with chemotherapy for patients with recurrent platinum-resistant ovarian cancer. Based on the time of submission, Genentech, the company that markets the drug, announced an FDA action date of November 19, 2014.
    [ The priority review was based on results from the phase III AURELIA trial .....

    *Crossover to single-agent bevacizumab was permitted after disease progression in patients in the chemotherapy-alone group.

    How can a true comparison of OS can't be arrived at for Avastin + chemo vs chemo alone for AURELIA when crossover to Avastin was allowed in the chemo alone group once progression set in? This is why primary endpoint of PFS will decide the FDA review, not OS, a secondary endpoint. Anyone still think that PFS in ovarian cancer does not matter, as I've read this view many times here, and that only OS does?

    The PFS results for Zybrestat/Avastin combo are gold.

  • Reply to

    Chemo plus Avastin Numbers

    by bullahoop Sep 21, 2014 9:52 PM
    shiteferbrains shiteferbrains Sep 22, 2014 9:48 AM Flag

    As per chemo alone arm in the AURELIA trial:
    At the time of data cutoff for the final overall survival analysis, 40% of patients in the chemotherapy-alone group had received single-agent bevacizumab after progression.

  • shiteferbrains shiteferbrains Sep 17, 2014 9:43 PM Flag

    Should read : Zybrestat/Avastin especially effective in ovarian cancer due to glucose deprivation?

    I forgot the question mark. Wasn't stating it as a certainty, but it is interesting, IMO.

  • Glucose molecules are delivered to cells by the circulating blood .........

    Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells

    Ovarian cancer cells are glycolytic as compared to normal, untransformed cells, and are sensitive to glucose deprivation.

    *The Z/Avastin combo is designed to destroy the existing and the to be built vasculature that supports the tumor. By cutting off the blood supply, glucose is prevented from reaching the ovarian cancer cells.

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