May 11, 2007
Dr. Andrew von Eschenbach
Commissioner, FDA
5600 Fishers Lane
Rockville, MD 20857
Subject: FDA Decision Regarding Provenge
Dear Dr. von Eschenbach,
I am usually not one to write letters to decision makers in our Government, though I served as a civil servant myself at NASA for 32 years. I do have, however, a sense of a public servant's responsibility to the American people whom I served. As a civil servant and the appointed leader of the FDA, charged with promoting the well being of Americans with respect to foods and drugs, I need to request that you explain to the people and their medical doctors why you chose not to approve Provenge, even though you were advised by your appointed panel of Oncologists, Urologists, and Immunologists, all experts in the fields of immunotherapy and oncology, that Provenge is unquestionably safe (100% of the experts voted yes on safety) and that there was “substantial evidence” of the drug's effectiveness as required by FDA regulations (76% of the experts voted yes on substantial evince of effectiveness). I must add that two of the no votes on efficacy came from two doctors who have conflicts of interest that your agency recognized before appointing them to the panel, and I must ask if they would have even been allowed to participate on the Provenge panel if FDA were now following its new guidelines on conflicts of interest? If no, then the vote without them would have been 13 to 2, or 86% in favor with regard to substantial evidence of effectiveness. I include these percentages since I know FDA is always very interested in statistics!
In walking away from the advisory panel votes on Provenge, I and the rest of older men who expect do battle with PC, would like a detailed public and scientific explanation of your decision. Certainly FDA has approved drugs against the recommendations of its advisory panel, but I am not aware of a decision to overrule a strong positive panel vote for a terminal illness that has no really acceptable treatment options. This decision would appear to be unprecedented, and calls for a full and open public statement of why the FDA disagrees with this panel and cannot make this drug available to terminal patients. We know of course it was not due to safety concerns. Also, if FDA found the clinical trial data ted by Dendreon to be insufficient, why did you even the data to a panel of experts for their opinions? This suggests the worst sort of scientific arrogance on the part of FDA regulators, or worse.
Let me offer several other reasons why a detailed public statement from you and your personal involvement to achieve a resolution is absolutely critical at this time. You have made many public promises that FDA would be a “bridge builder” and not a barrier. You could have built a bridge with Provenge by approving it with a post-marketing trial requirements, and allowing combination trials to be initiated with other treatments such as Taxotere. For example, Dr. Petrylak's analysis in The Urology Times pointed to a staggering survival benefit when Provenge is used with Taxotere. In fact, a 14-month survival advantage when compared to Taxotere alone. Surely you were informed of Dr. Petrylak's analysis? And then there is the Dendreon P-11 trial with early stage PC patients, showing a remarkable and clinically significant increase in PSA doubling time exceeding 40%. Surely FDA was told about this clinically significant benefit, were they not? Dr. von Eschenbach, the FDA said they wanted to see more data. How much is enough? Would you be turning away from this kind of data if the disease were breast cancer, instead of prostate cancer? Would you?
Dr. von Eschenbach, this decision by FDA can be, if you decide to do so, a bridge-building event. The credibility of FDA with the medical world is at stake here. You can build a bridge by being flexible with Dendreon as to additional data required for approval. Do something constructive here and do it quickly. Call in Dr. Petrylak, the Taxotere Principal Investigator, and those members of the AC panel who can serve now. Have the company present all of its existing trial data from other trials as well as those ted thus far. Allow the company to un-blind the on-going 9902b trial data to examine with you the TTP evidence using updated immunotherapy parameters instead of the outdated chemotherapy parameters that caused the TTP in the first Provenge trial to barely miss statistical significance, and “work with” this company to bring Provenge to market this year. Please don't walk away from this for several more years as we wait for the statistical picture to become more complete. It will never become a certainty. It will always be a probability. Your own statistician said the chance that the observed survival benefit in the completed trials occurring by chance and not by Provenge was only 1 in 50. Is this not enough to give you a reasonable comfort level sufficient to give Provenge to the 80,000 men who will die over the course of the next few years?
You have also told the medical research community that FDA would work to reduce the time and expense to bring new drugs to approval. Surely this must apply to Provenge, a treament for terminally ill cancer patients who have little time to live. Dr. von Eschenbach, do what you promised to do.
“TEAR DOWN THIS WALL!”
Be the leader we thought you to be. Be courageous. If you need to overrule ODAC and the chemo lobby, then do it. We have no champion but you. We have no voice but yours. Ronald Reagan did it in Berlin. You can do it in Washington.
Will you do the morally right thing and bring this first cancer immunotherapy to the people, even though your understanding of the science is less than perfect? Review again the tran of the March 29 meeting. Dr. Marincola and Dr. Pensen, who spoke from the public pulpit, urged you to consider the effect of your decision on cancer research. As did others at that table. You also have promised to encourage, not kill, cancer immunotherapies. Do what you promised, and talk to those on the panel who urged FDA to approve Provenge now so new trials could go forward. FDA desperately needs to understand that they must become partners with small biotech companies that cannot go on spending hundreds of millions of dollars to perfect the trial data beyond any shadow of a doubt. There is no unlimited source of funds. The law calls for substantial evidence, not absolute proof, of efficacy.
Become a partner with those whom you promised to serve , and those who depend on your cooperation as a regulator – the research community. These companies' scientists are giving their lives to save others. Surely you can give them your support. We are counting on you…..
God Bless You and Your Staff,
Joseph Sperty
2011 S Conference Dr.
Boca Raton, FL 33486
Dr. Andrew von Eschenbach
Commissioner, FDA
5600 Fishers Lane
Rockville, MD 20857
Subject: FDA Decision Regarding Provenge
Dear Dr. von Eschenbach,
I am usually not one to write letters to decision makers in our Government, though I served as a civil servant myself at NASA for 32 years. I do have, however, a sense of a public servant's responsibility to the American people whom I served. As a civil servant and the appointed leader of the FDA, charged with promoting the well being of Americans with respect to foods and drugs, I need to request that you explain to the people and their medical doctors why you chose not to approve Provenge, even though you were advised by your appointed panel of Oncologists, Urologists, and Immunologists, all experts in the fields of immunotherapy and oncology, that Provenge is unquestionably safe (100% of the experts voted yes on safety) and that there was “substantial evidence” of the drug's effectiveness as required by FDA regulations (76% of the experts voted yes on substantial evince of effectiveness). I must add that two of the no votes on efficacy came from two doctors who have conflicts of interest that your agency recognized before appointing them to the panel, and I must ask if they would have even been allowed to participate on the Provenge panel if FDA were now following its new guidelines on conflicts of interest? If no, then the vote without them would have been 13 to 2, or 86% in favor with regard to substantial evidence of effectiveness. I include these percentages since I know FDA is always very interested in statistics!
In walking away from the advisory panel votes on Provenge, I and the rest of older men who expect do battle with PC, would like a detailed public and scientific explanation of your decision. Certainly FDA has approved drugs against the recommendations of its advisory panel, but I am not aware of a decision to overrule a strong positive panel vote for a terminal illness that has no really acceptable treatment options. This decision would appear to be unprecedented, and calls for a full and open public statement of why the FDA disagrees with this panel and cannot make this drug available to terminal patients. We know of course it was not due to safety concerns. Also, if FDA found the clinical trial data ted by Dendreon to be insufficient, why did you even the data to a panel of experts for their opinions? This suggests the worst sort of scientific arrogance on the part of FDA regulators, or worse.
Let me offer several other reasons why a detailed public statement from you and your personal involvement to achieve a resolution is absolutely critical at this time. You have made many public promises that FDA would be a “bridge builder” and not a barrier. You could have built a bridge with Provenge by approving it with a post-marketing trial requirements, and allowing combination trials to be initiated with other treatments such as Taxotere. For example, Dr. Petrylak's analysis in The Urology Times pointed to a staggering survival benefit when Provenge is used with Taxotere. In fact, a 14-month survival advantage when compared to Taxotere alone. Surely you were informed of Dr. Petrylak's analysis? And then there is the Dendreon P-11 trial with early stage PC patients, showing a remarkable and clinically significant increase in PSA doubling time exceeding 40%. Surely FDA was told about this clinically significant benefit, were they not? Dr. von Eschenbach, the FDA said they wanted to see more data. How much is enough? Would you be turning away from this kind of data if the disease were breast cancer, instead of prostate cancer? Would you?
Dr. von Eschenbach, this decision by FDA can be, if you decide to do so, a bridge-building event. The credibility of FDA with the medical world is at stake here. You can build a bridge by being flexible with Dendreon as to additional data required for approval. Do something constructive here and do it quickly. Call in Dr. Petrylak, the Taxotere Principal Investigator, and those members of the AC panel who can serve now. Have the company present all of its existing trial data from other trials as well as those ted thus far. Allow the company to un-blind the on-going 9902b trial data to examine with you the TTP evidence using updated immunotherapy parameters instead of the outdated chemotherapy parameters that caused the TTP in the first Provenge trial to barely miss statistical significance, and “work with” this company to bring Provenge to market this year. Please don't walk away from this for several more years as we wait for the statistical picture to become more complete. It will never become a certainty. It will always be a probability. Your own statistician said the chance that the observed survival benefit in the completed trials occurring by chance and not by Provenge was only 1 in 50. Is this not enough to give you a reasonable comfort level sufficient to give Provenge to the 80,000 men who will die over the course of the next few years?
You have also told the medical research community that FDA would work to reduce the time and expense to bring new drugs to approval. Surely this must apply to Provenge, a treament for terminally ill cancer patients who have little time to live. Dr. von Eschenbach, do what you promised to do.
“TEAR DOWN THIS WALL!”
Be the leader we thought you to be. Be courageous. If you need to overrule ODAC and the chemo lobby, then do it. We have no champion but you. We have no voice but yours. Ronald Reagan did it in Berlin. You can do it in Washington.
Will you do the morally right thing and bring this first cancer immunotherapy to the people, even though your understanding of the science is less than perfect? Review again the tran of the March 29 meeting. Dr. Marincola and Dr. Pensen, who spoke from the public pulpit, urged you to consider the effect of your decision on cancer research. As did others at that table. You also have promised to encourage, not kill, cancer immunotherapies. Do what you promised, and talk to those on the panel who urged FDA to approve Provenge now so new trials could go forward. FDA desperately needs to understand that they must become partners with small biotech companies that cannot go on spending hundreds of millions of dollars to perfect the trial data beyond any shadow of a doubt. There is no unlimited source of funds. The law calls for substantial evidence, not absolute proof, of efficacy.
Become a partner with those whom you promised to serve , and those who depend on your cooperation as a regulator – the research community. These companies' scientists are giving their lives to save others. Surely you can give them your support. We are counting on you…..
God Bless You and Your Staff,
Joseph Sperty
2011 S Conference Dr.
Boca Raton, FL 33486
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