Although the FDA approved the Melanoma drug PLX 4032 (Zelboraf) on Wednesday (August 17, 2011), what is not in the news is that the FDA is responsible for lives lost by not allowing access two years or more ago to this drug for people who were fighting for their lives and could not get into clinical trials for this efficacious drug. This is nothing less than another clear avoidable FDA tragedy.
The Abigail Alliance for Better Access to Developmental Drugs first started pushing for earlier access to PLX 4032 two years ago. The Abigail Alliance keeps working to gain wider attention to the clear proof of the lifesaving and life-extending need for earlier access to promising developmental drugs.
This is the profound proof. Every drug for cancer and other serious life-threatening illnesses that the Abigail Alliance has pushed for earlier access to in our ten-year history is now approved by the FDA! There is not one drug that we pushed for earlier access to that did not make it through the clinical trial process.
The current count is 19 drugs and vaccines! EVEN the FDA’s own Science and Technology Board in their late 2007 report recommended there be a provisional approval mechanism for promising new drugs.
-Frank Burroughs, Founder and Steve Walker, Cofounder
Abigail Alliance for Better Access to Developmental Drugs
Last week, the Wall Street Journal published an article on the FDA which our President Frank Burroughs felt inclined to comment on. View the full article here “The FDA and Slower Cures” and read Frank’s reaction below.
The excellent Wall Street Editorial ‘The FDA and Slower Cures’ brings out some very important life saving and life-extending points, particularly the vital need to save patients’ lives as was done with AIDS drugs, the destruction of the accelerated approval process by Dr. Richard Pazdur along with his hand picked advisors, and the FDA’s unnecessary and deadly adversarial posture towards our innovative pharmaceutical industry.
The Abigail Alliance for Better Access to Developmental Drugs has been addressing this FDA tragedy foralmost ten years. Here is something that is very profound. Every drug for cancer and other serious life-threatening illnesses that the Abigail Alliance has pushed for earlier access to in our nine and half yearhistory is now approved by the FDA! There is not one drug that we pushed for earlier access to that didnot make it through the clinical trial process. Many lives could have been saved or extended, if there had been earlier access to these drugs! The current count is 17 drugs and vaccines! EVEN the FDA’s own Science and Technology Advisory Board in their late 2007 report recommended there be a provisional approval mechanism for promising new drugs.
The Abigail Alliance for Better Access to Developmental Drugs is happy to announce that there is now an expanded access program for the efficacious developmental metastatic melanoma drug PLX4032 (also known as RG7204 and RO5185426). Information regarding the program can be found on clinicatrials.gov at: http://www.clinicaltrials.gov/ct2/results?term=ml25597 , or by going to www.clinicaltrials.gov and searching for RO5185426.
The Abigail Alliance commends the sponsors Hoffmann-La Roche, its subsidiary Genentech, and Plexxikon for providing access to their breakthrough drug for the thousands of people diagnosed with metastatic melanoma who are, at this moment, fighting for their lives.
The Abigail Alliance has been communicating with the FDA and the sponsors with regard to this drug on behalf of patients. Among our several recommendations, we have pressed both organizations to open an expanded access program for PLX4032 as soon as possible. Please visit our website to learn more about our efforts to help people with metastatic melanoma gain access to PLX4032.
It should be noted that an unethical randomized trial that subjects terminal melanoma cancer patients to treatment with an old toxic drug in the control arm of a randomized trial (BRIM3 trial) is ongoing. The Abigail Alliance continues to urge the FDA and the sponsors to find an alternative to placing dying patients into a meaningless randomized trial control arm for no other purpose than to satisfy a rigid and ill-fitting regulatory policy, and move this drug toward approval as quickly as possible. This drug already solidly meets the Congressional and FDA standards for Accelerated Approval. The patients enrolled in the control arm of the trial are being denied their chance to benefit from this new breakthrough drug, and under the rules of the trial, will be allowed to die without ever being offered this breakthrough drug. The trial should be immediately stopped, and the control arm patients offered the new drug.
Frank Burroughs, President 703-646-5306
Steve Walker, Cofounder 813-340-3193
Abigail Alliance for Better Access to Developmental Drugs
On July 26th, the New York Times posted an editorial relating to the FDA’s decision on the drug Avastin. Their summary entitled “When a Drug Fails” missed the mark on so many levels that even on vacation, our co-founder Steve Walker felt compelled to respond.
This editorial reflects a typical lack of understanding of why the FDA granted accelerated approval for Avastin as a first-line treatment for breast cancer in the first place. Because there are now multiple approved treatments for metastatic breast cancer, with most women going on to treatment with several of them after their first line treatment stops working, it has become impossible to measure a first line drug’s effect on overall survival (how long a patient lives) after beginning treatment. The first trial of Avastin in this setting (on which its accelerated approval was based) indicated a significant advantage in delaying progression of the disease. The problem is obvious. Given the uneven response of patients to various drugs, and the FDA’s crude clinical trial standards designed only to measure and compare the average response of populations (as opposed to how individual patients benefit or don’t benefit from a drug), the FDA made the right call with Avastin (by approving it) the first time around. Think about it. A patient is treated with Avastin and may, or may not, benefit individually in terms of delayed progression or extended life, because the trials are not designed to try to learn whether the individual patient benefited. The FDA’s statistical trials, by design (a problem that cannot be fixed – it is an inherent limitation of statistics-based trials) cannot measure individual benefit. It can only measure the time to progression and the time to death of an individual, which is then dumped into a pool of those measurements from hundreds of patients in each trial arm, and used to calculate an average time to progression and an average time to death for the two populations (those who got Avastin and those who didn’t). They then compare the average outcomes (actually the average patient in one arm to the average patient in the other arm). Seem simplistic? It is. Each patient then goes on to be treated with multiple other drugs (but each patient’s experience is unique – different drugs in different orders, with very variable outcomes, and mostly outside clinical trials where measurements relevant to the initial trial with Avastin may or may not be accurately measured recorded), then at some point, they die. The patient lives, say, 18 months after being treated with four different drugs. Why did she live that long? Which drugs worked to extend her life, which ones didn’t? The FDA’s statisticians have no idea because the trials they mandate are designed far too simplistically to measure it, and it is the FDA that makes and enforces the expectations for trial designs, despite their frequent assertions to the contrary. The media’s consistently incorrect take on this, including in this editorial, is not surprising only because the media almost always fails to properly explain what happened. The most recent trials of this drug actually confirmed that there is a progression-free survival advantage, just not as much of an advantage as the first trial indicated, which means the drug is having a positive effect – on average, and it is still impossible to statistically measure overall survival for a first-line breast cancer drug. If they ran another trial, the result would show yet another progression-free survival result. The real problem here is not that Avastin doesn’t work – it is that FDA has long refused (actually for about 50 years) to update its clinical trial and regulatory science. Randomized controlled trials and the simplistic statistics that drive them, invented in the 1950′s at the FDA and written into law by Congress in 1962, aren’t working anymore. Just a small amount of progress in a still incurable form of breast cancer makes them unworkable. It is very difficult to make progress against a disease when FDA’s regulation has become so obsolete, we can’t even measure progress. With so much in the balance – more than half a million lives a year in the US alone – can’t we do better? We actually can, but resistance to real change at FDA is so profound, even getting started is proving to be an epic struggle. They are not saints over there. They are government employees following very old rules and policies in very formulaic ways and failing on a grand scale. Maybe you should write an editorial about that.
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- Access, Compassion, Care, and Ethics for Seriously Ill Patients Act or the ACCESS Act – Amends the Federal Food, Drug, and Cosmetic Act to require the Secretary of Health and Human Services to permit an investigational drug, biological product, or device to be made available for expanded access under a treatment investigational new drug application or treatment investigational device exemption if specified Compassionate Investigational Access requirements are met.
- Gives immunity to the manufacturer, distributor, administrator, sponsor, or physician from suit or liability relating to products approved under this Act. Establishes a procedure for accelerated approval of an investigational drug, biological product, or device that is reasonably likely to predict clinical benefit to a patient suffering from a serious or life-threatening condition.
- Requires the Secretary to establish:
(1) the Accelerated Approval Advisory Committee;
(2) a new program to expand access to investigational treatments for individuals with serious or life threatening conditions and diseases; and
(3) a demonstration project under the Medicare program to pay for drugs, biological, products, and devices approved under this Act.
- Amends title XVIII (Medicare) of the Social Security Act to revise the definition of “medically accepted indication” to provide for coverage of a covered Part D drug based on the sponsor’s or organization’s determination that the drug is for a medically accepted indication.
- Requires the Secretary to consider the clinical judgment and risks to the patient from the disease or condition in evaluating the safety and effectiveness of drugs, biological products, and devices that treat serious or life-threatening diseases or conditions, including the evaluation of nonstatistical information.
- Requires any committee evaluating investigational drugs, devices, or biological product applications to have at least two patient representatives as voting members.
Over at the Ayn Rand Center for Individual Rights, Thomas A. Bowden published a very insightful article related to our struggle.
Every life-threatening disease presents a health emergency to the individual patient. Morally, you have the right to seek the best treatment you can find. Yet our legal system denies you that right when it comes to private health emergencies.
The important point, as Frank Burroughs relayed in an email praising Bowden, is that tens of thousands of lives could and should be saved each year.
This Thursday, John Stossel’s show on Fox Business covered the question of whether or not the Government has the right to tell you what you can or can’t put into your body. The show featured comments from many sources on the subject including Frank Burroughs from the Abigail Alliance. John summarizes his thoughts on the matter on his site here. An excerpt:
Bruce Tower has prostate cancer. He wanted to take a drug that showed promise against his cancer, but the FDA would not allow it. One bureaucrat told him the government was protecting him from dangerous side effects. Tower’s outraged response was: “Side effects, who cares? Every treatment I’ve had I’ve suffered from side-effects. If I’m terminal it should be my option to endure any side-effects.”
Of course it should be his option. Why, in our “free” country, do Americans meekly stand aside and let the state limit our choices, even when we are dying ?
When online video of the full show becomes available, we will share.
Over the past couple years, there has been a battle raging to help get the drug Provenge approved by the FDA. Many people have brought up conflicts of interests among FDA panelists as reasons that Provenge has not been made available to the public as of yet.
Last week, Jim Edwards who writes the Pharma Analysis blog over at bnet.com wrote a piece titled SEC Probe Into Dendreon Cancer Drug “Conspiracy” Could Put Rumors to Rest. In the post, Jim writes:
The conspiracy theorists believe that the FDA was swayed by a “disparaging letter” about Provenge written by Scher to the FDA commissioner, and that coupled with his conflict of interest this maneuvering unfairly kept Provenge off the market — and doomed many men to die unnecessarily from prostate cancer.
On its face, it does look messy: It’s always bad to have people with conflicts of interest in positions of power.
But a closer look reveals that both Scher and Hussain’s conflicts were disclosed prior to their sitting on the panel, and Scher’s letter contains an entirely reasonable and highly persuasive argument for not approving Provenge at the time — the company didn’t have enough data.
In fact, Dendreon had only presented “secondary endpoint” results, not primary endpoints. In other words, they had cherry-picked their data from two studies in which Provenge failed to meet the primary endpoint goals.
Having read this, Frank Burroughs, President of the Abigail Alliance, felt compelled to respond to Jim in a note which I’ve included below. The Alliance definitely feels like these issues are real and it is important that people understand this fight.
What your article most certainly should have included was the lopsided FDA Oncologic Drugs Advisory Committee (ODAC) panel’s vote infavor of approving Provenge back in 2008. The ODAC was convinced prostate cancer patients were being helped by Dendreon’s vaccine.
Sadly your article downplayed Drs.Scher and Hussain’s serious conflict of interest. You should have been critical of the FDA for allowing them to be part of the Provenge review process in the first place.
Let me make one last note. Even if the FDA wants more data for Provenge and other drugs and vaccines, what is so vitally needed for patients fighting for their lives, who have run out of options, and like so many cannot get into a clinical trial is early access to drugs and vaccines like Provenge, before the final FDA approval. This is what the Compassionate Access Act will do that is close to being reintroduced in the U.S. Congress.
I think journalism gets measured by the quality of information it presents, not the drama or the pyrotechnics associated with us. – Bob Woodward
Please respond in comments if you guys have thoughts on this issue. We’d love to hear it!
With my fingers crossed, it looks like we are close to getting the ACCESS Act reintroduced in Congress and having help getting more momentum for adding more cosponsors this time around.
The Abigail Alliance has become part of a rare disease patient advocacy lobbying group put together by the Kakkis Foundation. This will help patients and help get more traction for the ACCESS Act.
Also recently, the Abigail Alliance has developed a closer relationship with BIO (Biotechnology Industry Organization). We are a significant and well received part of a project at BIO looking into ethical issues regarding earlier access to promising investigational drugs.