BW: What should the pharmaceutical industry do to improve its track record of getting drugs through the clinical trial process?
Pazdur: The real progress in cancer will be a better understanding of the molecular basis of the disease. Drug companies are very good at developing drugs. We're asking them to do something different here, which is to develop a better understanding of the disease. Traditionally, that has not been their major goal. But what we're looking at is a shift in the paradigm, an understanding of the disease process and how the drug works in relationship to that progress.
BW: The FDA is often criticized for being too conservative when it comes to cancer drug reviews, particularly by biotech companies. But these companies also lack regulatory experience. How would you apportion the blame, if any?
Pazdur: One of the things we have seen is a reluctance, sometimes, of smaller companies to make really critical decisions regarding their drugs, whether to curtail the development of a drug. Large companies, because they have a portfolio of drugs, generally if a drug fails to meet specified goals they'll look to abandon that drug -i.e., cut their losses. Whereas as a smaller company, if you only have one drug, then sometimes that is not an option. The big pharmaceutical companies don't want to waste their time with the FDA. They want to have a long-term relationship with the FDA. They certainly don't want to have to plea to the FDA that the drug should be used and marketed, even though it doesn't work, on an emotional basis.
BW: There is considerable discussion in the drug industry about looking at how a drug performs in subgroups of trial participants, even if it has failed to meet its goal in the larger trial. What is your view of this approach?
Pazdur: One of the problems we've had is people coming to us after a drug fails because they've invested millions and millions of dollars into a drug; and then it's, "How can we salvage this?" In other words, failing your primary endpoint and then trying to salvage a trial by looking at subgroups of patients. That's akin to shooting an arrow and having it land on a wall and then drawing a target around it. It's an attempt to resurrect a trial that has failed.
We have to have proof that a drug works. Its not: "Let's have a debate about whether the drug works." It's not: "Might the drug work?" The onus is on the sponsor to demonstrate that the drug works. We have numerous examples where people have come and argued with us that a subset shows efficacy, and subsequent trials were done and the subsequent trials failed to demonstrate efficacy.
BW: The FDA regularly uses panels of outside experts to advise it on cancer drugs, but sometimes seems to ignore the advisory panel's guidance. How do you explain that contradiction?
Pazdur: The advisory committee is advisory. Period. It is not a judge and jury. It is not the O.J. trial. It is not: "If the glove fits, you must acquit." It is the advice we are looking at, not the vote. We are more interested in the reasons why people are voting. We cannot approve drugs on the basis of emotion. It should be on the safety and efficacy being demonstrated. We are not moved by comments by committee members who say they want this drug approved because they say the approval will foster the development of a particular field.
BW: You treated cancer patients for decades. How do you respond to the emotional pleas from patients that drugs should be approved even if the evidence is shaky?
Pazdur: I grew up on the south side of Chicago. I'd hate to have some steel mill worker, from my father's generation, say "I spent all my life working in a steel mill, and I paid all my taxes for all of these years. I'm now dying from cancer and now my government is preventing me from getting the drug." It's heartbreaking to hear that, because it is a misrepresentation of the actual story. We can't make drugs available at the expense of lowering standards of approval. I don't think anyone wants to see drugs out there that don't work. I'd have a problem with that.
3 Comments
That's a great interview. I love the responce to his second question. I've spent some time at big pharma and at a biotech. He's right on the money: "One of the things we have seen is a reluctance, sometimes, of smaller companies to make really critical decisions regarding their drugs, whether to curtail the development of a drug. Large companies, because they have a portfolio of drugs, generally if a drug fails to meet specified goals they’ll look to abandon that drug -i.e., cut their losses. Whereas as a smaller company, if you only have one drug, then sometimes that is not an option."
Provenge and Our F.D.A.’s Overt Absent Of Loyality
Terminal patients are those who are not expected to live due to usually illness such as advanced cancer. If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness. Since such patients will likely die in a short period of time, treatment options, even if unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually.
Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease. Furthermore, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, the more difficult it is to treat such patients.
Yet innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as taxodere. The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only. This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.
Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as Urologists and Oncologists who treat such patients. While Provenge was on fast track status at this time at the FDA, the FDA panel recommended with clarity the approval of Provenge based on its proven and substancial efficacy and safety demonstrated in its trials, as they announced in March of 2007. Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!
Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without Merit and speculative claims about the treatment. Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.
Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge.
The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not remains completely unknown. What is known is that they are harming those they pledged to protect so long ago. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others.
“Facts do not cease to exist because they are ignored.” --- Aldous Huxley
Dan Abshear
Dan, Excellent comments!