Life Extension Magazine November 2010
As We See It
FDA Delay of One Drug Causes 82,000 Lost Life-Years
Reviewed and Critiqued by Stephen B. Strum, MD, FACP, Medical Oncologist Specializing in Prostate Cancer Since 1983
By William Faloon
In 2004, I wrote an article describing how Americans die needlessly because of the FDA’s delay in approving lifesaving drugs.1
One example of a delayed therapy I cited was Provenge®, which in the year 2002 had demonstrated improved survival in prostate cancer patients.2
In 2007, Dr. Stephen Strum and I co-authored an article showing how enormous numbers of lives could be spared if scientists were liberated from oppressive FDA over-regulation. We described several cancer drugs that should have been approved including Provenge®, which by the year 2007 had extended survival in several clinical studies.3
In 2010, the FDA finally approved Provenge®.4 This was after still another FDA-mandated clinical trial documented the efficacy of this therapy.
As you’re about to read, the FDA’s eight-year delay in approving Provenge® has resulted in a horrific number of prostate cancer victims prematurely dying!
How Effective Is Provenge®?
Once the FDA finally approved Provenge® in April 2010, the news media hailed it as a miracle new cancer therapy. What the media failed to convey was the fact that Provenge® was not new. It had been discovered almost a decade earlier. Despite the impressive study results you are about to read, the FDA denied it for eight long years.
In an analysis from the first study in 2002, Provenge®-treated men with a less aggressive prostate cancer (Gleason score 7 or less) were eight times more likely to live six months without disease progression compared to placebo.2
After 30 months, these same patients receiving Provenge® were 3.7 times more likely to be alive. This translates into 53% of the Provenge® group surviving compared to only 14% of the placebo group. The Provenge® group also remained pain-free twice as long on average as the placebo group.2,3
The FDA refused to recognize these findings and ordered the company to conduct more clinical studies. We at Life Extension® were livid at the time over the FDA’s decision to deny prostate cancer patients access to this therapy.
Fast forward to 2005, and the results of a new clinical study showed that three times as many advanced prostate cancer patients who received Provenge® were alive compared to patients receiving a placebo.5,6 This study evaluated 127 patients with prostate cancer that did not respond to androgen-deprivation therapy. Cancer experts consider this patient subset to have a dismal prognosis, with most dying of the disease within a few years. In this Provenge® study, 34% of the patients receiving Provenge® were still alive after three years compared to only 11% of men who were randomly assigned a placebo.5 The FDA again refused to approve Provenge®, even with this kind of data in hand.
In the most recent study on advanced prostate cancer patients, Provenge® prolonged median survival by 4.5 months and produced a greater than threefold increase in survival at 36 months compared to placebo.7
As I’ll explain later, any improvement in survival in advanced cancer cases is viewed favorably as these patients have already failed grueling conventional therapies. We postulate that if used earlier in the disease process and in combination with other non-toxic therapies, Provenge® will be far more effective.
Based on this latest study and in conjunction with the other prior favorable studies, the FDA approved Provenge®—eight years later than it should have!
How Many Life-years Lost Because of FDA’s Delay?
Prostate cancer killed 27,360 American men in 2009.8 This is down from prior years where it used to kill around 30,000 Americans. Earlier diagnosis is one reason for this decline. Far fewer men are diagnosed with advanced prostate cancer with bone metastases today because of PSA testing.
In determining how many human life-years have been lost because of the FDA’s delay in approving Provenge®, we would come up with very high numbers if we only used data from the most favorable studies.
Instead, we choose to use the least favorable data that looked only at median survival improvement in those with advanced stage prostate cancer who were no longer responding to conventional therapy.
We took the low number of 27,360 men who died of prostate cancer in 2009 and multiplied it times the 4.5 months of improved survival demonstrated in the latest study. The total number of human life-years lost each year the FDA delayed approving Provenge® comes out to 10,260.
Multiply the eight years the FDA delayed approving Provenge®, and the total number of lost life-years is a startling 82,080.To state this statistic differently, 82,080 lost life-years translates to 1,066 entire lives lost. This calculation is based on taking the 82,080 lost life-years divided by average male life expectancy of 77 years.
The federal government refuses to consider Life Extension’s longstanding recommendation of making FDA approval voluntary, as opposed to the compulsory process it is today.
If prostate cancer victims had access to Provenge® when it first demonstrated efficacy in 2002, 82,000 human life-years could have been spared.
Provenge® Is Just One of Many Delayed Drugs
The cover story of the September 2007 issue of Life Extension Magazine® was titled “Life-saving Cancer Drugs Rejected by the FDA.” In that issue, we meticulously described several anti-cancer drugs (including Provenge®) the FDA had not yet approved. All of these drugs had substantial scientific evidence indicating efficacy. We argued that since terminal cancer patients had no other options, they should be allowed access to these therapies.
In the case of Provenge®, an FDA advisory panel recommended it be approved in the year 2007.9,10 FDA bureaucrats, however, ignored scientists on this advisory panel and mandated that more studies be done.
FDA Delay Makes Provenge® Cost-prohibitive
Had Provenge® been made available in year 2002 like it could have been, it might be available at a more reasonable price today. The FDA’s insistence on multiple redundant clinical studies will result in the therapy costing $93,000 per patient.
It is doubtful that all insurance companies will reimburse for Provenge® therapy. Either way, consumers will pay for the FDA’s delay in the form of higher medical insurance premiums, higher taxes, and/or having to pay for the drug out of pocket.
As we have stated many times, a key factor in today’s healthcare financial crisis is that medical progress and efficiency are obstructed by bureaucratic delays leading to hyper-inflated costs.
We Were Not the Only Ones Screaming for Provenge® to Be Approved
The FDA was put under enormous pressure to approve Provenge® ever since the first successful clinical study came out in the year 2002. After a second study showed even greater efficacy, prostate cancer support groups, scientific organizations, and even mainstream publications demanded that the FDA grant terminal patients the right to try this therapy.
The January 26, 2004 issue of the Wall Street Journal featured an editorial stating:
“We know that it works, and we know why it works. In any rational regulatory environment, that would be reason to speed Provenge® to market.”11
By 2007, there was a revolt underway against the FDA for continuing to reject Provenge®, including threats by members of Congress to conduct a full scale investigation and lawsuits filed by patient support groups. FDA bureaucrats, however, steadfastly refused to budge (until April 29, 2010).12
Even though Provenge® therapy is now officially approved, it will only be available to treat about 2,000 patients over the next year.13 That’s because it requires specialized laboratories to be established throughout the United States to take each cancer patient’s blood and create an individualized vaccine. The problem is that more than 27,000 men will die of prostate cancer over the next twelve months, meaning that fewer than 8% of these fellow human beings will have access to Provenge® before they die.
How the FDA Stifles New Cancer Drug Development
When an experimental therapy prolongs life by only a few months in advanced cancer cases, the public often assumes the treatment is of little value.
The reason new cancer therapies often show mediocre results in clinical studies are FDA mandates that these new drugs only be tested in advanced-stage patients who have failed currently approved therapies. This creates a major obstacle because therapies that might cure cancer (or induce durable remissions) if used in earlier stages may be ineffective in advanced stages of the disease.
Once the drug is approved, however, it can be used (off-label) sometimes more effectively in treating earlier-stage disease patients. It can also be used in combination with other therapies to yield better survival results, something that is usually not allowed in clinical trial designs the FDA tightly controls.
The reason that it is so difficult to kill advanced-stage, treatment-resistant cancers is that they have mutated and acquired multiple survival mechanisms. These advanced-stage cancer cells are thus extremely difficult to eradicate with any therapy.
Now that Provenge® has been approved by the FDA, innovative oncologists can prescribe it to early-stage prostate cancer patients whose cancers have not developed a resistance to androgen deprivation therapy. These earlier-stage patients may respond better than the advanced hormone refractory cases that the drug was tested on in the clinical trials.
When one understands the many roadblocks the FDA erects against promising cancer treatments, it becomes clear why more effective therapies have not been discovered to eradicate this insidious disease.
In an ideal setting, Provenge® would have been made available to those who wished to “opt-out” of the FDA’s regulatory stranglehold, and we would have learned long ago how effective Provenge® therapy was against a wide range of prostate cancers.
At this point, we don’t even know how effective Provenge® will be outside the clinical study setting. Not all drugs shown effective in tightly controlled studies are as efficacious in the real-world, which is another reason to get drugs out faster in order to enable those dealing with real-world cancer patients to ascertain safety and efficacy.
FDA Interference Worse Than What Most Experts Think
For the past 30 years, Life Extension has identified effective medications that languished too long in the FDA’s archaic approval process.
When lifesaving new drugs are delayed, the inevitable consequence is needless human suffering and death. An equally insidious problem is the chilling effect that bureaucratic roadblocks have on the development of better drugs that might cure the disease.
Just imagine the difficulty of raising the tens of millions of dollars needed to get a new cancer drug into the approval pipeline when prospective investors see the FDA delay a drug with documented efficacy for eight years, as was done with Provenge®.
Another problem with the FDA’s unpredictable approval pattern is the outrageous cost of cancer drugs that do make it to market. Insurance companies do not always pay for these new drugs, thus forcing desperate cancer victims to pay out-of-pocket for new drugs that can exceed $12,000 per month. The media has reported on heart-wrenching stories of cancer patients who choose to die rather than condemn their families into bankruptcy in order to pay these costs.
It’s easy to point fingers at drug companies for charging such extortionist prices, but the harsh reality is that getting these medications approved by the FDA is so costly and risky that the high prices can arguably be justified by the inefficient drug approval process that now exists.
Why Drugs Like Provenge® Take So Long to Approve
The fundamental problem with today’s byzantine drug approval process is bureaucratic inefficiency and corruption.
What the public does not understand is that when a new therapy like Provenge® is being considered for approval, companies selling older (less effective) drugs have a tremendous incentive to block the better medicine. It can be quite cost-effective to persuade the FDA to erect barriers against newer therapies that compete with highly profitable existing drugs. Allegations ran rampant that the FDA delayed Provenge® because large pharmaceutical companies did not want to lose revenue from toxic chemotherapy drugs that advanced prostate cancer patients were forced to use in lieu of Provenge®.
Bureaucratic ineptitude has been highlighted by the failures of the Securities and Exchange Commission (SEC) to prevent widespread financial fraud.14 As you may know, even when outsiders conducted meticulous investigations and handed cases like that of Ponzi schemer Bernie Madoff to the SEC on a silver platter, the SEC did nothing to stop Madoff from defrauding more victims.
When complaints are made about FDA drug delays, a kneejerk response from some in Congress is “we need to give the FDA more money.” It is regrettable that politicians can’t see past the simple fact that providing more money and power to incompetent and corrupt agencies results in more incompetence and corruption.
This Is No Longer a Debatable Issue
Provenge® is by no means the first drug Life Extension recommended years or decades before the FDA permitted it to be sold to Americans. For example, we fought for nearly two decades to force the FDA to approve ribavirin as an adjuvant treatment for hepatitis C and low-dose aspirin for heart attack prevention. In both cases, we faced criminal investigations by FDA agents who felt it more productive to put us in jail rather than approve these lifesaving therapies.
Sadly, most of the drugs Life Extension has identified as having probable efficacy are never allowed on the American market because the sponsor company runs out of money jumping through the FDA’s impossibly high regulatory hurdles.
The FDA now says (in 2010) that Provenge® is effective in prolonging survival in men with advanced prostate cancer. That means the drug was also effective in the year 2002, when the FDA first suppressed it.
With Provenge® (and many other drugs), there is nothing more to debate. The FDA’s delay of this one drug caused the equivalent loss of over 1,000 entire lives. This is the same as terrorists killing 1,000 newborn babies, yet no one in the media even suggested that the FDA was tardy in approving Provenge®. Americans can no longer tolerate this ongoing atrocity, either from a financial or morality standpoint.
What You Can Do to Stop Needless Cancer Deaths
Scientists have identified novel ways of treating cancer, but too little of this new technology is being used in clinical practice. When new discoveries are made, drug companies spend years seeking a patent, and then more years carrying the drug through the cumbersome bureaucratic approval process. A major reason so many cancer patients die today is an antiquated regulatory system that causes effective therapies to be delayed (or suppressed altogether).
This system must be changed if the 1,500 American cancer patients who perish each day are to have a realistic chance of being saved.
Our longstanding proposal has been to change the law so that anyone can opt out of the FDA’s umbrella of “protection.” This approach will allow companies to sell drugs that have demonstrated safety and a reasonable likelihood of effectiveness, which are clearly labeled “Not Approved by the FDA.” Patients who wish can still use only FDA-approved drugs, while those willing to take a risk, in consultation with their doctors, will be allowed to try drugs shown to be safe that are still not approved.
We believe that this initiative will result in a renaissance in the practice of medicine similar to the computer technology revolution of the past three decades. In the liberated environment we propose, many lethal diseases will succumb to cures that are less expensive than is presently the case. And greater competition will help eliminate the health care cost crisis that exists today.
Today’s broken system results in terminally ill people learning of scientific discoveries that might well cure their disease, but sadly hearing their newscaster say the therapy is years away from FDA approval. We think that seriously ill people, in consultation with their doctors, should be able to make up their own minds about what drugs they are willing to try.
Tell Congress You Want the Law Changed!
For the past three decades, Life Extension has sought to expose an insidious drug approval process that causes human beings to die, even though effective therapies to treat their diseases already exist.
The FDA is able to suppress innovative therapies because the public has failed to demand that our elected officials rein in the FDA’s arbitrary authority. The first step in changing today’s outmoded system is to communicate the urgent need for change to Congress.
A bill titled the Compassionate Access Act of 2010 (H.R. 4732) has been introduced into the House of Representatives.16 This bill would amend the Food, Drug, and Cosmetic Act to create a new conditional approval system for drugs, biological products, and devices for seriously ill patients.
While this bill will not enable patients to “opt-out” of the FDA’s regulatory stranglehold, it is an important first step that will demonstrate that human lives can be spared if earlier access to experimental therapies is permitted.
I urge all Life Extension supporters to use our convenient Legislative Action Center to ask your Congressional Representative to co-sponsor the Compassionate Access Act of 2010 (H.R. 4732). Passage of this legislation will enable cancer patients (and others with serious diseases) to obtain therapies far enough along in the clinical trials process to be deemed safe, but not yet approved by the FDA.
We at Life Extension have long contended that any person with a serious illness should have the individual right to choose therapies that have not yet received official FDA approval.
For the benefit of yourself and your loved ones, please use our convenient system to contact your Representative about the critical need to co-sponsor the Compassionate Access Act of 2010. You can easily contact your Representative today by logging on to the Legislative Action Center.
For longer life,
Stephen B. Strum, MD, FACP
1. Faloon W. Are you afraid of terrorists? Life Extension Magazine®. 2004 Jun;10(6).
2. Available at: http://findarticles.com/p/articles/mi_m0EIN/is_2002_Dec_11/ai_95190631/. Accessed June 29, 2010.
3. Faloon W, Strum S. FDA rejects promising prostate cancer drug. Life Extension Magazine®. 2007 Sept;13(9).
4. Available at: http://www.fda.gov/News Events/Newsroom/PressAnnouncements/ucm210174.htm. Accessed August 4, 2010.
5. Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trialof immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94.
6. Available at: http://www.psa-rising.com/med/immun/provenge-05.htm. Accessed August 5, 2010.
7. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9.
8. Available at: http://www.medicinenet.com/script/main/art.asp?articlekey=100730. Accessed August 5, 2010.
9. Available at: http://www.cnn.com/2010/HEALTH/04/27/provenge.prostate.cancer.fda/index.html. Accessed August 5, 2010.
10. Available at:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm210174.htm. Accessed August 5, 2010.
11. New cancer drugs. Wall Street Journal. January 26, 2004.
12. Available at: http://caretolive.com/2008-01-20/fda-under-pressure-from-congress-to-explain-provenge-delay/. Accessed June 29, 2010.
13. Available at: http://www.medscape.com/viewarticle/721160. Accessed July 1, 2010.
14. Available at: http://www.dailyfinance.com/story/media/how-madoff-got-away-with-it-sec-report-phone-transcript-reveal/19156812/. Accessed July 1, 2010
15. Available at: http://www.cnn.com/2010/POLITICS/04/23/sec.porn/index.html. Accessed July 2, 2010.
16. Available at: http://www.abigail-alliance.org/S_3046_ACCESS_Act.pdf. Accessed July 2, 2010.