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    Old 04-14-2009, 08:50 AM   #1
    IADT3since2000
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    Smile Provenge success !!!!! Awesome news !!!!!

    It's now official: the Phase III clinical trial of the immune system drug Provenge was a success!!!!!

    This was pretty dramatic - no sure thing at all. Based on results at the interim, the goal had not yet been reached. For those of us "watching from the stands," it was like a horse race with our favorite well back in the stretch but coming on strong and finishing triumphantly! (I could almost see Eliza Doolittle bellowing her famous encouragement.)

    The bottom line: probably with a year, the prostate cancer survivor community should be getting access to a new, effective drug for lengthening survival for those at greatest risk of dying from prostate cancer: men with metastatic, hormonal-therapy resistant prostate cancer.

    I looked at the news release from Dendreon (the developer and manufacturer) a little before 9:00 AM Eastern time this morning, and then listened to the conference call. In essence: Provenge satisfied its standard for success in a fairly large (512 patients), gold-standard type of clinical trial (meaning randomized with the drug and a placebo, and "double-blinded" - neither the staff working with the patient nor the patient knew if he was getting the drug or the placebo).

    For those of us who want more details about the trial itself, it was known as IMPACT, standing for IMunotherapy for Prostate Advanced Cancer Treatment. I was not able to find much information at www.pubmed.gov, a site we can use on this board because it is Government sponsored. A treasure trove of information about the previous clinical trial and FDA hearing are available at another site we can use on this board (again because it is Government sponsored): http://www.fda.gov/ohrms/dockets/ac/cber07.htm#CellularTissueGeneTherapies . The documents for the Provenge hearing are included under the dates March 29-30.

    The previous trials were reported as showing a survival benefit of about 4.5 months, which does not seem like much considering the cost of the treatment. However, there are two key points to keep in mind. First, that figure of 4.5 months is an average that includes all results from both patients who responded to the therapy and those who did not. Well, in trials, those who respond have a much better response than the average response figure. In other words, the results from the non-responders water-down the average. In actual clinical practice, when a patient does not respond to a drug that is tried, the oncologist can tell that fairly quickly, within one to three months usually as I understand it, and switch to some other approach. Second, the past and current trial use a "cross-over" design. That means that the patients in the placebo arm get access to a version of the investigated drug later in the trial, after they showed evidence of disease progression. The impact on results is that in a sense the investigated drug is competing against itself, and that somewhat reduces differences in results between the treatment groupd and the so-called placebo group.

    Another thing to remember is subtle. Typical survival for men with hormone refractory (meaning hormonal therapy no longer fully controls the cancer), metastatic prostate cancer but who do not yet have symptoms ("asymptomatic") - the grouping of men who were patients in this clinical trial - in one encouraging study turned out to be 40 months for men with mets in the bones and 68 months if there were no mets in the bones yet (Oefelein, Agarwal and Resnick, 2004). (Moreover, this study was based on patients treated some time ago - before important key advances in treatment - survival should be even better today! )

    However, clinical trial researchers for this grouping of men (no longer responding to hormonal therapy and with metastasis but without symptoms) usually talks about typical survival being just about 18 to 20 months. They do this for a practical reason: often, they don't know the exact date a man stopped responding to hormonal therapy; therefore, as a practical convention, they use the date of a man's entry into a trial as the starting point for counting survival, and so that all men are counted on the same basis, they do it for men whose true dates of hormonal resistance are known. This, of course, results in a shorter survival period than the true survival period. Unfortunately, I've found that many doctors, researchers and media reporters do not understand the difference between much more favorable true survival and the artificial but practical version of survival used for trials.

    Effectiveness. Dendreon's CEO, Mitch Gold, said that the results were a solid, robust hit, and that they confirmed the less robust results from their favorable but smaller, earlier clinical trials. He said the results were clear and unambiguous, adding that they held up to a number of "sensitivity analyses." (Sensitivity analysis involves checks to see if the favorable results can be explained by causes other than the drug.) CEO Gold added that the follow-up period in this trial was probably the longest for men with advanced prostate cancer.

    Safety. He also said that safety results, which had looked highly favorable in the previous trials, were similar. (About 1,000 men have been involved in Provenge trials to this point, apparently.) Here's a brief excerpt from the press release on safety: "In controlled clinical trials, the most common adverse events were chills, fever, headache, fatigue, shortness of breath, vomiting and tremor. These events were primarily low grade with a short duration of 1-2 days following infusion." The paper published by the Eric Small group on a previous Provenge trial with 127 patients said that side effects included rigors (59.8% versus 8.9% for placebo), pyrexia (?) (29.3% versus 2.2% for placebo), tremor (9.8% versus 0% for placebo), and feeling cold (8.5% versus 0% for placebo). They commented that 9%% of patients received all three planned infusions, and no patient had to drop out of the trial because of toxicity. This profile of side effects is in sharp contrast to the profile for chemotherapy drugs.

    The company did not go into details of the trial results today because those details are "embargoed" until they are presented at the annual conference of the American Urological Association in two weeks: their timeslot for presentation is April 28 at 2:20 PM. No doubt we will get some media coverage then.

    Because the company had an agreement on a "Special Protocol Assessment" with the FDA, success in the trial smoothes the way for approval. From this point, the interactions with the FDA should be straightforward, more-or-less working out routine details, as I understand it. No more research will be necessary, though the company has other trials in process to assess whether the drug would be worthwhile for other groups of prostate cancer survivors, particularly those with earlier stages of the disease.

    Moreover, the company manufactured its trial drug from the same facility it will use for the final drug. The company said it expects a smooth scaling-up from the current experimental production level to full-scale production. My understanding is that the manufacturing process has been pretty much established, with just a few final tweaks needed.

    Here's one more point to watch for when the detailed results are published in two weeks: how the patients do who have had both Provenge and docetaxel, the latter being the key standard chemotherapy medication for such patients at present. While one of the great attractions of Provenge is that the side effects are fairly mild compared to chemotherapy, thus giving the promise of enabling men to avoid those rough side effects, earlier Provenge trials indicated that men getting both drugs had substantially better survival - better than for docetaxel without Provenge, and even better than for Provenge alone.

    Please keep in mind that I am a layman survivor with no enrolled medical education or any first hand knowledge of the drug or the company. I'm basing my comments on what I have learned from the media, from the FDA hearing on Provenge, and from talks and newsletters intended for prostate cancer survivors.

    A great day for all of us - Jim

    Last edited by IADT3since2000; 04-14-2009 at 09:05 AM. Reason: Right after posting added sentence about the dramatic aspect of the result. Then added emphasis for first sentence.

     
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    Old 04-14-2009, 03:25 PM   #2
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    Re: Provenge success !!!!! Awesome news !!!!!

    Yes thats great news for many men with high risk advanced cases. Hope its made available ASAP and lives up to its promise. IT WILL HAVE MUCH WIDER APPLICATION THAN P.C. IF IT REALLY PROVES OUT IN THE LONG RUN.

     
    Old 04-14-2009, 06:31 PM   #3
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    Re: Provenge success !!!!! Awesome news !!!!!

    Quote:
    Originally Posted by IADT3since2000 View Post
    It's now official: the Phase III clinical trial of the immune system drug Provenge was a success!!!!!

    This was pretty dramatic - no sure thing at all. Based on results at the interim, the goal had not yet been reached. For those of us "watching from the stands," it was like a horse race with our favorite well back in the stretch but coming on strong and finishing triumphantly! (I could almost see Eliza Doolittle bellowing her famous encouragement.)

    The bottom line: probably with a year, the prostate cancer survivor community should be getting access to a new, effective drug for lengthening survival for those at greatest risk of dying from prostate cancer: men with metastatic, hormonal-therapy resistant prostate cancer.

    I looked at the news release from Dendreon (the developer and manufacturer) a little before 9:00 AM Eastern time this morning, and then listened to the conference call. In essence: Provenge satisfied its standard for success in a fairly large (512 patients), gold-standard type of clinical trial (meaning randomized with the drug and a placebo, and "double-blinded" - neither the staff working with the patient nor the patient knew if he was getting the drug or the placebo).

    For those of us who want more details about the trial itself, it was known as IMPACT, standing for IMunotherapy for Prostate Advanced Cancer Treatment. I was not able to find much information at www.pubmed.gov, a site we can use on this board because it is Government sponsored. A treasure trove of information about the previous clinical trial and FDA hearing are available at another site we can use on this board (again because it is Government sponsored): http://www.fda.gov/ohrms/dockets/ac/cber07.htm#CellularTissueGeneTherapies . The documents for the Provenge hearing are included under the dates March 29-30.

    The previous trials were reported as showing a survival benefit of about 4.5 months, which does not seem like much considering the cost of the treatment. However, there are two key points to keep in mind. First, that figure of 4.5 months is an average that includes all results from both patients who responded to the therapy and those who did not. Well, in trials, those who respond have a much better response than the average response figure. In other words, the results from the non-responders water-down the average. In actual clinical practice, when a patient does not respond to a drug that is tried, the oncologist can tell that fairly quickly, within one to three months usually as I understand it, and switch to some other approach. Second, the past and current trial use a "cross-over" design. That means that the patients in the placebo arm get access to a version of the investigated drug later in the trial, after they showed evidence of disease progression. The impact on results is that in a sense the investigated drug is competing against itself, and that somewhat reduces differences in results between the treatment groupd and the so-called placebo group.

    Another thing to remember is subtle. Typical survival for men with hormone refractory (meaning hormonal therapy no longer fully controls the cancer), metastatic prostate cancer but who do not yet have symptoms ("asymptomatic") - the grouping of men who were patients in this clinical trial - in one encouraging study turned out to be 40 months for men with mets in the bones and 68 months if there were no mets in the bones yet (Oefelein, Agarwal and Resnick, 2004). (Moreover, this study was based on patients treated some time ago - before important key advances in treatment - survival should be even better today! )

    However, clinical trial researchers for this grouping of men (no longer responding to hormonal therapy and with metastasis but without symptoms) usually talks about typical survival being just about 18 to 20 months. They do this for a practical reason: often, they don't know the exact date a man stopped responding to hormonal therapy; therefore, as a practical convention, they use the date of a man's entry into a trial as the starting point for counting survival, and so that all men are counted on the same basis, they do it for men whose true dates of hormonal resistance are known. This, of course, results in a shorter survival period than the true survival period. Unfortunately, I've found that many doctors, researchers and media reporters do not understand the difference between much more favorable true survival and the artificial but practical version of survival used for trials.

    Effectiveness. Dendreon's CEO, Mitch Gold, said that the results were a solid, robust hit, and that they confirmed the less robust results from their favorable but smaller, earlier clinical trials. He said the results were clear and unambiguous, adding that they held up to a number of "sensitivity analyses." (Sensitivity analysis involves checks to see if the favorable results can be explained by causes other than the drug.) CEO Gold added that the follow-up period in this trial was probably the longest for men with advanced prostate cancer.

    Safety. He also said that safety results, which had looked highly favorable in the previous trials, were similar. (About 1,000 men have been involved in Provenge trials to this point, apparently.) Here's a brief excerpt from the press release on safety: "In controlled clinical trials, the most common adverse events were chills, fever, headache, fatigue, shortness of breath, vomiting and tremor. These events were primarily low grade with a short duration of 1-2 days following infusion." The paper published by the Eric Small group on a previous Provenge trial with 127 patients said that side effects included rigors (59.8% versus 8.9% for placebo), pyrexia (?) (29.3% versus 2.2% for placebo), tremor (9.8% versus 0% for placebo), and feeling cold (8.5% versus 0% for placebo). They commented that 9%% of patients received all three planned infusions, and no patient had to drop out of the trial because of toxicity. This profile of side effects is in sharp contrast to the profile for chemotherapy drugs.

    The company did not go into details of the trial results today because those details are "embargoed" until they are presented at the annual conference of the American Urological Association in two weeks: their timeslot for presentation is April 28 at 2:20 PM. No doubt we will get some media coverage then.

    Because the company had an agreement on a "Special Protocol Assessment" with the FDA, success in the trial smoothes the way for approval. From this point, the interactions with the FDA should be straightforward, more-or-less working out routine details, as I understand it. No more research will be necessary, though the company has other trials in process to assess whether the drug would be worthwhile for other groups of prostate cancer survivors, particularly those with earlier stages of the disease.

    Moreover, the company manufactured its trial drug from the same facility it will use for the final drug. The company said it expects a smooth scaling-up from the current experimental production level to full-scale production. My understanding is that the manufacturing process has been pretty much established, with just a few final tweaks needed.

    Here's one more point to watch for when the detailed results are published in two weeks: how the patients do who have had both Provenge and docetaxel, the latter being the key standard chemotherapy medication for such patients at present. While one of the great attractions of Provenge is that the side effects are fairly mild compared to chemotherapy, thus giving the promise of enabling men to avoid those rough side effects, earlier Provenge trials indicated that men getting both drugs had substantially better survival - better than for docetaxel without Provenge, and even better than for Provenge alone.

    Please keep in mind that I am a layman survivor with no enrolled medical education or any first hand knowledge of the drug or the company. I'm basing my comments on what I have learned from the media, from the FDA hearing on Provenge, and from talks and newsletters intended for prostate cancer survivors.

    A great day for all of us - Jim

     
    Old 04-14-2009, 06:39 PM   #4
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    Re: Provenge success !!!!! Awesome news !!!!!

    Thanks for all the research. I hurried in a posting this morning without noticing you had posted a notice of conference call. I startled to see the company's symbol going across the ticker. It was like watching...using your analogy...the long shot horse come down the stretch like Secretariat. This sounds like a possible break through...that fit your impression? I am old enough to recall how we feared polio and avoided the community swimming pool...and saw lives devastated without any effective treatment...and then the break through. Wouldn't it be, as shs50, says be good if this success is an effective breakthrough for patients at diverse stages...or a preventive measure.

     
    Old 04-15-2009, 11:24 AM   #5
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    Re: Provenge success !!!!! Awesome news !!!!!

    Jim:
    I have a friend who may not be able to wait a year for Provenge but who's still asymptomatic and negative for bone mets but is metastatic to lymph nodes and hormone refractory. Had to discontinue Taxetere therapy as side effects were unsustainable.
    Do you know how he or his oncologist could get access to Provenge before general distribution? He's up in New Hampshire and really can't travel down to NY. He's being cared for at Dartmouth-Hitchcock M.C.
    Bob

    Last edited by shs50; 04-15-2009 at 12:04 PM.

     
    Old 04-15-2009, 03:00 PM   #6
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    Re: Provenge success !!!!! Awesome news !!!!!

    Quote:
    Originally Posted by dale2035 View Post
    ...
    Wouldn't it be, as shs50, says be good if this success is an effective breakthrough for patients at diverse stages...or a preventive measure.....
    There's a story in today's Wall Street Journal- lots more details to come.
    Dendreon's common stock has more than doubled, but one would need to have bought a lot of it at the low price it to be able to easily afford this treatment, at least at the beginning. The story mentioned the annual cost might be $50,000. Hopefully that will come down quickly, but more importantly, related drugs that might work can also be developed.

     
    Old 04-20-2009, 06:29 PM   #7
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    Re: Provenge success !!!!! Awesome news !!!!!

    Quote:
    Originally Posted by dale2035 View Post
    ... This sounds like a possible break through...that fit your impression? I am old enough to recall how we feared polio and avoided the community swimming pool...and saw lives devastated without any effective treatment...and then the break through. Wouldn't it be, as shs50, says be good if this success is an effective breakthrough for patients at diverse stages...or a preventive measure.
    Hi Dale, Bob, daff and friends,

    Yes, I believe it is a breakthrough for the group of patients that responds. While it is far from being a cure, the added survival is substantial if the results we will learn on April 28 are similar to the results from the two earlier trials, and that is the way Mitch Gold, Dendreon's CEO, compared the results. If I were a patient doing well enough to be able to take advantage of the treatment when it comes available next year, I would feel I had a good shot of adding a lot of months to my life.

    Bob - I don't know how a patient could get early access other than being able to qualify for one of the Provenge trials that is now recruiting. However, with FDA approval seeming to be a fairly sure thing, Dendreon may try to set up an early access program. There was some discussion of such a program at the time of the FDA hearing in 2007. Also, Dendreon now has trials underway to see if the drug works for prostate cancer patients with less advanced cases. Dendreon has mentioned that the drug may work for other cancers too.

    Most of the following information is based on the two earlier trials, and to keep that key fact clear, I'm putting the rest of this post in brown.

    The larger of the two earlier trials of Provenge showed a survival advantage of 4.5 months (25.9 months versus 21.4 months). Well, 4.5 months is a nice advantage, especially when it is better than the current standard for chemotherapy, but keep this vital point in mind: the average of 25.9 months includes all patients getting Provenge - those who responded to the drug, and those who did not. The average survival would be substantially higher if just the responders were counted!

    Unfortunately, I don't think that data has been published. However, the handouts at the FDA advisory committee hearing also showed that 34% of the Provenge group was alive at 36 months while only 11% of the placebo group was alive at that point, which provides some indication of the much greater success for the responders! I'm hoping that the information on the new trial will include the percentages of responders versus non-responders and give us survival information for both groups.

    I am especially eager to hear results for the group of patients that at some point had docetaxel in addition to Provenge. While Provenge extended survival more than the standard, much harsher, chemo treatment involving docetaxel (Taxotere), a team involving renowned researchers Eric Small, MD, at UCSF, and Daniel Petrylak, (Memorial Sloan Kettering?) observed that the patients getting a combination of Provenge and docetaxel had an unusually large increase in survival. Eighty two of the patients in two earlier trials happened to receive Taxotere following their treatments in the trials. Those patients who had had the clinical trials' version of Provenge and later had Taxotere benefited from an average survival of 34.5 months, nearly three years! (Again, remember that that figure is an average of those who responded to Provenge, to Taxotere or to both, and to neither; the survival would almost surely be much better for those who clearly responded to both of the drugs. Also keep in mind that some of those men are still alive, so that average survival figure will grow larger as time goes by. )

    Those patients who did not get the trial version of Provenge had the option, once their cancer had progressed, of getting a frozen version of Provenge; their survival was 25.7 months. In contrast, the 32% of men getting the placebo who decided not to get the frozen Provenge but who did get later Taxotere had an average survival of 20.2 months, substantially shorter.

    We need to keep in mind what the survival numbers mean in a more practical and more encouraging sense - true survival is longer than reflected in the trial, even for the group that did best. First, the numbers are for men with "hormone refractory" (basically meaning: the cancer no longer is controlled by hormonal therapy - PSA is rising despite castrate level of testosterone), metastatic prostate cancer but without symptoms yet. Second, the starting date for the survival count is the date the men enter the clinical trial - not the date that they actually become hormone refractory!

    There is not a lot of information on the true length of average survival for such men - men whose true dates of becoming hormone refractory are known, but one study found that the average was 40 months if the men had bone mets at the time of becoming refractory and 68 months if they did not. (Oefelein, Agarwal, Resnick, 2004) And, those men were treated quite a few years ago, before several important advances that would almost certainly substantially extend survival.

    You may be wondering why clinical trials do not routinely use the true dates that men become refractory to measure survival. First, clinical trials use the artificial date of clinical trial entry for hormone refractory disease because it is practical: often the true date is not known. Provided the numbers of men in each group in the clinical trial are large enough, differences in true times since becoming refractory should average out, meaning it is unlikely that trial results would be a chance result of men with short spans since becoming refractory being dominant in one arm of the study while men with long spans since becoming refractory happened to be dominant in the other arm of the study. A second reason is that the trial usually wants to determine the time of survival starting near a key event, such as, in this case, getting the Provenge or placebo treatment. That means you are counting a shorter survival span than you would if you also included the time each man became refractory up to the time he entered the trial.

    Also, it's worth keeping in mind that many of the patients in the recent Provenge trial are still alive. Hopefully they will stay alive for a long time so we won't be able to average their survival times, even with the artificial starting points, into the trial averages for a long time - inconvenient for science, but a triumph for us patients! But when that day finally comes that we can average in their actual success, we should see some pretty long survivals.

    Jim

     
    Old 04-21-2009, 05:47 PM   #8
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    Re: Provenge success !!!!! Awesome news !!!!!

    Thanks Jim:
    My friend was told by Dartmouth Hitchcock M.C. that Provenge is only available as a study drug in clinical trials in which D.H.M.C. is not a participant. So he'll have to wait for FDA approval. They also forwarded a website which reported controversey over Dendreon's optimistic press release. Another oncologist a Dr. Coy or some similiar name took issue with the reports of early approvals and suggested that that they had a lot more to prove before approval. Whereupon other Dr's jumped on this claiming he was an unethical tool of the Dendreon short sellers and Hedge Funds that shorted the stock.
    Who knows where the truth lies? Its such a shame that a potentially life extending drug is caught up in stock market manipulations and regulatory politics.
    Where's the downside in making it available as an experimental therapy for advanced cancer sufferers who have little to lose and who knows how much to gain? What happened to the FDA's much vaunted fast track approval process for life saving drugs?

     
    Old 04-22-2009, 11:41 AM   #9
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    Cool Re: Provenge success !!!!! Awesome news !!!!!

    Hi Bob,

    Thanks for this update. I'm inserting some comments in green. Jim


    Quote:
    Originally Posted by shs50 View Post
    Thanks Jim:
    My friend was told by Dartmouth Hitchcock M.C. that Provenge is only available as a study drug in clinical trials in which D.H.M.C. is not a participant. So he'll have to wait for FDA approval.

    I'm sure we can all sympathize with him. How awful it must be to know that there is a likely lifeline just out of your reach and that time may be running out. However, you might suggest that he call Dendreon and see if something could be worked out along early access lines. It's at least worth a try. Based on the trial results (see below) and what I remember from the April 2007 FDA advisory committee hearing, I think there is a fair chance he might succeed. He should keep this in mind: it won't be just him contacting the company. At the hearing I recall one of the speakers saying that about 50,000 men were in circumstances like his, and I just read a 4/14/2009 AP article by Marilynn Marchione quoting Dr. William Oh that 40,000 to 60,000 men at this time have widespread prostate cancer. I believe that Dendreon will at least listen sympathetically, but that's just my impression based on no connection or communication with the company.

    They also forwarded a website which reported controversey over Dendreon's optimistic press release. Another oncologist a Dr. Coy or some similiar name took issue with the reports of early approvals and suggested that that they had a lot more to prove before approval. Whereupon other Dr's jumped on this claiming he was an unethical tool of the Dendreon short sellers and Hedge Funds that shorted the stock.
    Who knows where the truth lies? Its such a shame that a potentially life extending drug is caught up in stock market manipulations and regulatory politics.

    I'll go out on a limb and state that I am highly confident the detailed results will be as encouraging as Dendreon's CEO Mitch Gold indicated a week ago. That's not just an impression; I'm listing five key points below. A word about me - while I am biased because I have a case of advanced prostate cancer that is not curable by current technology (though controllable, and I'm doing very well, thank you!), I have never had a financial stake in either Dendreon or its competitors, have received no benefits from them and expect none (other than, possibly, someday from their products), and have had virtually no communication with them. (That may change: I plan to request that they cover certain points in their AUA presentation, and I have a few other thoughts for rolling out Provenge to patients.)

    First, Dendreon, like any publicly traded company, is under strict Securities and Exchange Commission rules about its public statements about its products, research and prospects. One of the key reasons for the rules is to prevent insider trading; it is vitally important for the welfare of our stock markets that all investors have access to key information at the same time. Deliberate misstatements are subject to large fines and, I believe, jail time. Those rules would obviously motivate CEO Gold and other Dendreon officials to be truthful. I'm sure all of them are mindful of what happened to Martha Stewart and others in the ImClone scandal.

    Second, for this IMPACT trial, unlike the previous two trials, a very simple endpoint was used: survival, or, bluntly, death. In the previous trials, the primary endpoint was delay in disease progression, and that is a whole lot tougher to measure, partly because what to count and how to count it are a lot more subjective and still tentative, based on the state of the art. (I can provide more detail if anyone would like to have it, based on attending the Provenge hearing in April 2007 and previous FDA events, including a workshop on prostate cancer endpoints.)

    Third, the IMPACT trial results complete the hat trick for Provenge trials: three for three in extending survival! That consistency alone is worth a lot. I'm a rusty statistician, but I suspect there are ways to address all three results as a whole, and I'm confident that such an analysis would increase the robustness of the evidence that Provenge is effective.

    Fourth, in view of the SEC requirement to give all investors access to key information at the same time, and in view of Dendreon's natural, business-responsible desire to have the details achieve prominence before a large and credible professional audience, holding the details for just two weeks from the initial announcement until next week's AUA meeting is the right thing to do. Maybe, just maybe, the media that so often ignore or nearly bury news of great interest to a large audience of older men will not be able to bury the news about Provenge from the AUA conference. We need this news about Provenge's success to get out, not only to patients, but also to families of patients, to doctors, to researchers and to policymakers! My paper, the Washington Post, did not cover last week's announcement at all. Nor did I see any coverage on network news, though it's possible I missed it. The New York Times ran a story on it, but only in the business section. The AP did run a good story on it. Hopefully all major media outlets will do a good job covering the detailed results. I hope to post more about that shortly.

    Fifth, Dendreon CEO Gold's statements were remarkably succinct, brief, clear-cut, and to the point: in a word, convincing. He said things like (my recollection, my language) the results were a clear hit, that the endpoint was convincingly achieved, and that the results were robust and unambiguous.

    Therefore, I consider it highly unlikely that CEO Gold's very clear and simple statements about the trial's success will be proven false or misleading when details are announced next week on April 28 at the American Urological Association's annual conference.


    Where's the downside in making it available as an experimental therapy for advanced cancer sufferers who have little to lose and who knows how much to gain? What happened to the FDA's much vaunted fast track approval process for life saving drugs?
    My recollection is that Provenge was on the fast track, and I think that Dendreon had production limitations that moved it away from exploring wider access as experimental therapy once early approval was not given. I was at the key hearing, made a survivor-representative statement to the advisory committee in favor of recommending approval, and applauded favorable comments by the committee during the final discussion phase of the hearing. However, what I learned at the hearing had diminished my enthusiasm and confidence that the drug would be approved. Obviously, I could not help being biased in favor of what looked like a promising drug, but it was obvious at the hearing that the results were somewhat ambiguous and that the evidence was not fully convincing; the evidence was "substantial", which became a key word at the hearing, but not completely convincing. I actually believe the FDA did a good and professional job in reviewing Provenge. I also believe that medical oncologists Hussain and Scher, who played key roles in the FDA's decision not to approve the drug in 2007, were sincere, professional and insightful in their comments, though I was also impressed by those advisory committee members who voted for approval. It was a very tough, very high stakes (lives, not Wall Street $, though those too) judgment call. Waiting for what will turn out to be two to two and a half years from April 2007 before FDA approval surely will have cost quite a few advanced prostate cancer patients many months of added survival , but the research completed during that delay will have also greatly boosted confidence in the drug, not only among patients and their doctors, but also among the important groups I mentioned before and others: family members, researchers, policy makers, media reporters and editors, and even voters. That is very important!

    Jim

     
    Old 04-24-2009, 11:02 AM   #10
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    Re: Provenge success !!!!! Awesome news !!!!!

    Jim:
    I tried contacting Dendreon and couldn't even get through to a live person. "Leave a message". Their website did not offer any info about access outside of a clinical trial which has no participating center in or near New Hampshire.
    Thanks Again,Bob

     
    Old 04-27-2009, 08:12 PM   #11
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    Re: Provenge success !!!!! Awesome news !!!!!

    Quote:
    Originally Posted by shs50 View Post
    Jim:
    I tried contacting Dendreon and couldn't even get through to a live person. "Leave a message". Their website did not offer any info about access outside of a clinical trial which has no participating center in or near New Hampshire.
    Thanks Again,Bob
    Hi Bob,

    This may be the trial you are writing about, but it looks like one your friend might want to consider - for men with hormone refractory metastatic prostate cancer. There is a site in New York that is recruiting for this trial - not that far from New Hampshire.

    I haven't seen the Government's clinical trials website used on our board before, but I assume it's okay to use here because it is Government sponsored and therefore in line with the posting policy.

    http://www.clinicaltrials.gov/ct2/show/NCT00715078?term=Provenge&recr=Open&rank =1

    I'm really looking forward to getting details of the IMPACT trial for Provenge that will be announced less than 24 hours from now - at 2 PM at the American Urological Association annual meeting in Chicago. I hope the media do a decent job of coverage - not always the case for our PC survivor issues.

    Take care,

    Jim

     
    Old 04-29-2009, 06:00 PM   #12
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    Re: Provenge success !!!!! Awesome news !!!!!

    Thanks Jim:
    Unfortunately the closest trial site is in NYC and my friend can't make the trip for the necessary # of visits and monitoring. However today's press conference for investors announced that Dendreon is confident of FDA fast track approval and expects to have supplies in the hands of urologists and oncologists by summer 2010 or earlier. The treatments are three weekly injections done at the Dr's office and will cost$50,000 which they believe Medicare will pay. Most candidates will be covered by Medicare. Nothing was said about whether private insurers will go for the cost. Sounds hopeful and I think my friend can hang on as it hasn't metastasized to the bones and was only in two lymph nodes and he's still asymptomatic.with a Gleason 9 going on 5 years.
    Sounds like a quantum improvement over Taxetere which had serious side effects and didn't extend survival very long.
    Thanks again, Bob

    Last edited by shs50; 04-29-2009 at 06:02 PM.

     
    Old 04-29-2009, 07:38 PM   #13
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    Re: Provenge success !!!!! Awesome news !!!!!

    Yesterday around 2 PM the Dendreon Corporation made history by announcing details of successful completion of the large, Phase III trial for Provenge at the annual meeting of the American Urological Association (AUA) in Chicago. Provenge became the first active immunotherapy to demonstrate improvement in overall survival for advanced prostate cancer.

    This was the news we had been waiting for, and by now I have spent hours studying the slides for the talk presented by Dendreon and listening to a replay of a conference call after the presentation at the AUA about the trial. The bottom line: the details live up to the encouraging brief announcement of success by Dendreon two weeks ago. I've been around research results for prostate cancer for a number of years now and have become pretty good at seeing flaws in studies, but this study looks sound to me.

    Personally, I'm impressed and delighted. This is a great time for prostate cancer survivors - especially for patients with very advanced disease, their families, and physicians treating the disease. It is gratifying to all of us who were rooting for this drug from the sidelines and sometimes the frontlines, such as at the FDA advisory committee hearing two years ago.

    Here are some of the facts about the trial and its results, and I may be able to answer questions about other facts. Just to briefly repeat information from earlier on this thread, the trial involved

            Scoring was based on length of "overall survival" from time from randomization to either the Provenge arm of the study or the placebo arm, and neither the patient nor the staff treating him knew whether he was getting Provenge or the placebo. (In research terminology, that made the study "double blind".) Twice as many of the 512 patients were assigned to the Provenge arm (341 patients) as to the placebo arm (171). Virtually all research studies lose some patients so that they can no longer be followed, and this study was no exception; however, only six patients were lost to followup, which strikes me as an exceptionally low number, especially for a large group of patients with such advanced disease, and is only 1.1% of the total. The rules for the trial were renegotiated with the FDA in 2002, and enrollment resumed at that time.

            When the dust cleared at the end of the trial:

                      Now, with the results in, doctors and researchers can start working on how to get even better results from more patients. For starters, all of such late-stage patients with bone mets should be on a bisphosphonate drug, probably the powerful drug Zometa, in my layman's opinion.

                      There's more to tell about these wonderful results, but this is enough for today from me. If you have learned more about the results, please pitch in.

                      These are exciting days!

                      Jim

                      Last edited by IADT3since2000; 05-01-2009 at 04:51 PM. Reason: Found out what hyperhydrosis was (excessive sweating) and pyrexia (fever), and HTLV1 and inserted the meanings in the text.

                       
                      Old 04-30-2009, 04:11 PM   #14
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                      Re: Provenge success !!!!! Awesome news !!!!!

                      Great synopsis Jim.

                       
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