Latest Drugwonks' Blog
What makes Bob Temple so endearing (and his opinions so enduring) is his blunt truth telling. Alas, he is often the Cassandra of White Oak.
Recently Temple stated his belief that regulations on product promotion should not impede companies from rebutting findings from comparative effectiveness research involving their products.
This may not sound like a big deal – but it’s a clarion call for those who understand the imperative to systematically and scientifically counter the counter-detailing efforts coming thanks to the tens of millions of tax dollars earmarked for such efforts by the Patient Protection and Affordable Care Act (PPACA).
According to the Pink Sheet, “The subject of asymmetry in the reporting and commenting on CER findings has been a key point of discussion for NPC as CER has taken on a more visible role within the health care debate. Some suggest manufacturers of products subject to CER might have difficulty discussing the findings of the research given FDA restraints on commercial speech.”
Perhaps not.
Speaking at the February 9th conference, Asymmetry in the Ability to Communicate CER Findings: Ethics and Issues for Informed Decision Making (hosted by the National Pharmaceutical Council and cosponsored by the National Health Council and WellPoint), Temple said there is “no FDA view … that drug companies are condemned to silence about their products outside of formal promotion or perhaps published articles. If there’s something published that seems wrong, is based on poorly designed meta-analysis and so on, I don’t see any impediment to answer that and companies do answer that all the time."
Indeed, Bob seemed surprised and displeased that industry has sat by while the grand poobahs of comparative effectiveness share their questionable conclusions.
According to Dr. Temple, “A recent example might be newspaper assertions that antidepressants have no long-term benefit and really don’t work. This has been published repeatedly, and I’d like to see a rebuttal from the people who make antidepressants, because I think the published reports … are wrong. [FDA] may get around to rebutting, but somebody else might want to, and I don’t think there is any impediment to doing that."
Pedal to the metal? Not so fast. Bob qualified his remarks by saying (appropriately) that companies should be mindful of how FDA regulates speech when (and if) they decide to rebut wrong or misleading information from a comparative effectiveness research (whether or not it’s government-funded). “It is clear to me that a sponsor could correct or dispute a CER statement by a payer, or even the government, as long as the correction was not itself promotional."
And there’s the rub. Just what does “promotional” mean – and who is to judge?
Temple gives a good example of how to avoid such a problem:
“In recent months, we’ve seen companies disagree publically with meta-analyses, with epidemiologic conclusions they considered unsupported on methodologic grounds, and that’s OK, although making their own [conclusions] probably would not be."
In other words, it’s not “promotional” to point out a comparative effectiveness study’s design flaws and, therefore, the errors of its conclusions. If such an approach is “compliant,” it opens up tremendous opportunity in countering so-called “academic” detailing.
Or does it? Temple’s is a powerful voice inside the FDA – but it is only one voice. If Secretary Sebelius’ interference in the agency’s Plan B decision is any indication – might not his view be similarly overturned by the mandarins in the Humphrey Building? After all, the comparative effectiveness studies under debate are funded by PPACA and fielded by the Agency for Healthcare Research and Quality (AHRQ). And, to put it bluntly, the current administration has not looked kindly on those who question either its philosophical motives or legislative methods. Industry is deemed guilty until proven guilty. The current modus operandi seems to follow Franz Kafka’s statement that, “My guiding principle is this: Guilt is never to be doubted.”
Which brings us back to the question, what does promotional mean?
A recent paper by Coleen Klasmeier (a former FDA attorney and currently the head of Sidley Austin’s FDA regulatory practice), addresses this issue head on. She points out that “The FDA approach is one of delicate balance – of forbidding off-label promotion without undue incursion into the ability of physicians to obtain information about off-label uses from manufacturers.”
This issue of “undue incursion” seems to dovetail nicely with Bob Temple’s notion of focusing on design flaws and incorrect conclusions. But what of intent?
Well – intent is in the eyes of the beholder. Where one person might see a robust discussion of study design, another might see promotional intent. The foundational problem, as Klasmeier eloquently points out, is the FDA’s reliance on “multifactorial tests rather than bright-line standards.”
Plainly stated, regulators at the FDA (and particularly those who must address thorny First Amendment issues) embrace ambiguity over predictability. It gives them almost limitless power. Industry, on the other hand, wants and needs an evidence-based regulatory framework that provides predictable standards for their communications efforts. Bright lines. Predictability is power in pursuit of the public health. Minus such an effort, we get the troubling example of Par Pharmaceuticals.
In a pending First Amendment suit against the FDA, Par contends the government is criminalizing it’s speech to healthcare professionals about the on-label use of its appetite suppressant Megace ES (megestrol acetate) in settings where doctors prescribe the drug for both approved and unapproved uses.
Par’s complaint, filed Oct. 14 in the U.S. District Court for the District of Columbia, seeks a preliminary injunction against government enforcement of FDA labeling regulations on the grounds they are harming Par’s First Amendment rights by chilling protected speech.
Par’s suit states that physicians more frequently prescribe the drug to treat wasting in non-AIDS geriatric and cancer patients and that the majority of prescriptions for the drug are for off-label uses.
Par also seeks a declaratory judgment that it may speak about the approved use to physicians who could prescribe it for that use, even if they are more likely to prescribe the drug for off-label uses.
“Common sense dictates that the government cannot justify censoring a broad swath of truthful and valuable speech regarding lawful activity out of a desire to prevent other lawful activity,” a memorandum in support of the motion for preliminary injunction states. “And it is absurd to think that the government may imprison a person for engaging in truthful speech about a lawful activity that the government itself subsidizes.”
At issue in Par’s suit are provisions in the Food, Drug, and Cosmetic Act concerning “intended use” of a drug and misbranding.
“If a manufacturer speaks about the on-label use of its drug in a setting where the manufacturer knows that physicians prescribe the drug off-label, the government interprets the FDA’s ‘intended use’ regulations to deem the manufacture to be expressing an ‘objective intent’ that physicians prescribe the drug off-label,” Par’s memorandum states.
In a press release announcing the suit Par said it hoped to “elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care.”
Atlas was permitted the opinion that he was at liberty, if he wished, to drop the Earth and creep away; but this opinion was all that he was permitted. – Franz Kafka
If a company can be challenged when it discusses strictly on-label uses of a product, how much more convoluted, challenging and intimidating will it be to challenge a government-funded and government-detailed comparative effectiveness study?
Disputing comparative effectiveness studies – or any research for that matter -- need not fall into the chasm of promotion (off-label or otherwise). To lump scientific discourse into this slippery silo is to court both agency action and political attention. Alas, as Klasmeier writes, “The off-label problem reflects the accretion of administrative interpretations over the years.”
“Accretion” – otherwise known as mission creep.
Klasmeier continues, “… the commercialization of an investigational new drug is not to be construed to interfere with a manufacturer’s entitlement to engage in scientific exchange.”
And isn’t debating the flaws of a research study scientific exchange -- even if (and especially when) such exchanges raise questions about conclusions that are contrary to any given company’s marketing and sales objectives? How does the issue of intent play into compliance when legitimate scientific exchanges also impact promotional considerations?
On which side should regulators err?
The answer is as easy as it is difficult – regulators should err on the side of the public health. And perhaps the best precedent is FDAMA Section 401, which expressly permits companies to provide reprints of peer-reviewed medical journal articles on off-label studies (as long as they have a pending supplemental application with the agency).
But – as a word to the wise – let’s remember the astute observation of William Blake that, “A truth that’s told with bad intent, beats all the lies you can invent.”
Obama's Nurse Ratched
By Robert M. Goldberg on 2.16.12 @ 6:07AMThe American Spectator
Behind every powerful health care mandate under Obamacare is a power-hungry woman named Kathleen Sebelius. As the Health and Human Services Secretary, she has unprecedented power under Obamacare to control health care decisions, the approval of medical products and the national biomedical research agenda. The Secretary is not only the key player; she is the only one on the field. "The Secretary shall…" is mentioned more than 1000 times in the new health care law.
Sebelius is using that power to promote a liberal agenda and Obama's re-election.
She pushed the contraception edict. Her staff wrote the rules that decided Catholic hospitals and charities are not religious institutions. And she was the one who came up the with the "accommodation" in response to resistance to the mandate: just make the health plans pay for it even if the customers of the plan don't want it.
It is clear Sebelius cares only about imposing a worldview and policies to win support for Obamacare. A reporter asked Sebelius: "If a Catholic nonprofit is paying for your insurance coverage, isn't it paying for contraception if you are getting the coverage through that same insurer?"
Sebelius: "The federal employees health plan… costed this as no cost, free, no cost, because adding contraception and having some employees take advantage of that coverage lowers the overall cost of the health plan."
Free? She will tell insurers to suck up the cost and still force religious organization to offer the benefit. Or else.
This is not an aberration. It is quintessential Kathy: She rules by fiat and if you cross her she will crush you. And when she rebukes and bullies, Sebelius, like Nurse Ratched, claims she is doing so for our own good. As the Big Nurse said: "We do not impose certain rules and restrictions on you without a great deal of thought about their therapeutic value."
In 2002 Sebelius was the insurance commissioner in Kansas and campaigning for governor. She blocked the sale of Blue Cross Blue Shield to Anthem Health because she "thought" doing so would raise premiums. In 2003 when Sebelius was elected, Anthem decided against the merger. (Meanwhile, from 2000-2009 premiums in Kansas rose nearly 100 percent.)
Her use of power during the last days before a congressional vote on Obamacare was also Ratched-like in nature: Sebelius told the Association of Health Insurance Plans: "You can choose to continue your opposition to reform. If you do and reform goes down in defeat, we know what will happen." She threatened insurers that if they continued to blame their rate increases on the new health overhaul they could be excluded from health insurance exchanges.
Sebelius subsequently hauled in health plan execs in 2010 to explain why premiums were going up by 10-20 percent in certain states. And she tried to censor one health plan altogether when it sent a letter to Medicare customers about premium increases. She explained she was only doing this in ensure everyone gets basic care. Or a Nurse Ratched would say: "I tell you this hoping you will understand that it is entirely for your own good that we enforce discipline and order."
Last year Sebelius appeared at several fundraisers for Democrat congressional candidates and the 2012 re-election effort. Sebelius broke all campaign spending records in the 2006 re-election bid and she is regarded as a fundraising machine. In part this is due to the fact that the used the power of her office to punish enemies and reward pals. As HHS Secretary she has the power to mandate coverage, exclude health plans, reject payment for new technologies. She has shown she's not afraid to use this power to shake down and intimidate groups holding views contrary to her own and reward her allies. And since the Independent Payment Advisory Commission reports to her, she has absolute control over what Medicare and Medicaid will pay for in the years ahead.
Which is why Sebelius (who attacked Super PACs in 2010) is one of Obama's most important surrogates in the effort to raise outside money for his re-election. She has spoken at Planned Parenthood and the National Abortion Rights Action League events. Sebelius has attended fundraisers for several politicians over the past two years. And in the process she will use Obamacare as both carrot and stick to get her way.
Illinois State Reps. Ann Williams (D) and Edward Acevedo (D) introduced a bill in the state's General Assembly that would limit the substitution of a biosimilar for a prescribed product by Illinois pharmacies. The bill (HB5581) would permit substitution only when five criteria are met: the biosimilar has been determined by FDA to be interchangeable with the prescribed product; the prescribing physician does not specifically prohibit substitution; the patient provides written consent for the substitution; the pharmacist notifies the prescribing physician in writing within 24 hours after the substitution; and the pharmacy and the prescribing physician retain a written record of the substitution for no less than five years.
ABC News
Cancer patients are furious that a counterfeit version of the drug Avastin has landed in U.S. clinics.
Avastin, which is made by the California-based company Genentech, is used in combination with chemotherapy to treat cancers of the colon, brain, kidneys and lungs. But the counterfeit lacks the tumor-starving ingredient some patients need to survive.
"It's an outrage," said Diane Barraza, 48, who takes Avastin for stage IV colon cancer. "For a company to sell this drug, put it in our blood, it's an outrage."
The U.S. Food and Drug Administration announced Tuesday that 19 clinics in California, Texas and Illinois may have purchased the phony Avastin from Quality Specialty Products, an "unapproved" foreign supplier also known as Montana Health Care Solutions. The counterfeit vials are labeled "Avastin" but indicate "Roche" as the manufacturer. Roche is the parent company of Genentech.
"The counterfeit contains no Avastin, no generic Avastin, no active ingredient whatsoever," Genentech spokesman Ed Lang told ABC News. Lang said the contents of the vials are still under investigation.
For patients like Barraza, a fake cancer drug would be the cruelest con.
"To sit in the chemo chair and watch that stuff drop into my veins," said an emotional Barraza, who lives in Fullerton, Calif., with her 6-year-old daughter. "It's all I've got. And it might just be water?"
Avastin is expensive, costing upwards of $650 for a small vial. But Montana Health Care Solutions sold the counterfeit vial for $480, according to one of the clinics -- a cost savings of 25 percent.
"Obviously it makes good business sense to try to get the drug at a reduced cost," said Dr. Jack Jacoub, a medical oncologist at Orange Coast Memorial Medical Center in Fountain Valley, Calif. "But when you start to get drug pricing that's markedly different from that of the standard distributor, it should raise a red flag."
Only four U.S. distributors are authorized to sell Avastin to doctor's offices; another four can sell the drug wholesale to hospitals. Montana Health Care Solutions is not an authorized Avastin distributor. Jacoub, who treats Barraza, said his clinic buys Avastin in bulk from an approved distributor for $593.20.
Montana Health Care Solutions claimed to be based in Belgrade, Mont. But the company's recently disconnected phone number has a New Brunswick, Canada, area code. It's unknown whether Montana Health Care Solutions knew the Avastin was counterfeit. They also sold other cancer drugs, including Neulasta and Faslodex, at a significantly discounted price.
The FDA was alerted to the possible counterfeit in December 2011 by the Medicines and Healthcare Products Regulatory Agency in the U.K., according to Genentech's Lang. In a Feb. 10 letter, the agency urged the 19 clinics known to have purchased through unapproved distributors to "retain and secure" any unused drugs. The counterfeit Avastin vials have the lot numbers B86017, B6011, B6010, and the labels are slightly different.
Counterfeit or illegally imported drugs are rare in the U.S. but not unheard of. In 2008, heparin (a blood thinner) imported from China killed 81 Americans.
"Counterfeit drug makers have reached a level of sophistication where the real and fake products look almost identical," said Peter Pitts, president of the Center for Medicine in the Public Interest and former associate commissioner for the FDA. Pitts estimated that counterfeit drugs generated $75 billion in 2010, a figure expected to grow by 20 percent annually. "It's a low risk, high reward proposition. It's almost a perfect crime -- people aren't getting the drugs they need and they end up dying."
For Barraza, who will have four more Avastin treatments over the next two months, the thought of criminals profiting from her disease is sickening.
"I wish they could understand what it feels like to be a cancer patient, to take a drug and to suffer," she said. "I'd do anything to stay alive, but I need the right medication."
Read the full article here.
Sometimes you need to state the obvious to make a point. Or as Steve Martin once said: "A day without sunshine is like, you know, night."
Such it is with cough and cold medicines. A survey CMPI conducted on consumer use of such medications confirmed what we likely think we already know:
• Two-thirds (66%) of surveyed adults and 70% of surveyed parents rely on OTC cough medicines to treat their own and their children’s symptoms.
• Over the past year more than half of U.S. adults (57%) have taken cough medicines and 71% of parents have administered these medicines to their children aged four and older.
• 75% of consumers agree that OTC medicines provide relief of their cough symptoms so they can get a good night's rest.
• 68% of consumers agree that OTC medicines allow them to stay productive at work or school when they are not feeling well.
• 61 million consumers in the past 12 months have avoided missing work, school, or other scheduled appointments due to illness because they had access to OTC cough medicines to alleviate their symptoms (based on census data).
Not suprisingly, consumers like the freedom to get such medicines without waiting or paying for a doctor:
o 78% of consumers believe that it would place a burden on them and their family because they would need to visit a doctor.
o 74% of consumers believe that it would place a burden on them and their family because they would need to take time away from other responsibilities, such as work or school.
o 71% of consumers believe that it would limit their ability to provide care for their children.
o As such, 76% of consumers believe OTC cough medicines should remain available over-the-counter without restrictions.
The vast majority of Americans use cough and cold formulations because they are a save, convenient and affordable way to stop coughing. And when you cough you -- or your children and people around you -- are uncomfortable, can't sleep, can't work. And if we had to run to the doctor and get a prescription for every time we coughed or were stuffed up we would be spending a lot more money treating symptoms that, more often than not, resolve are their own. Then again, running to the doctor, especially a pediatrician is just a figure of speech. These days running to the doctor is like, well, not getting an appointment for days, sitting in an office with other parents and really sick kids, reading magazines that are so old they still have Mel Gibson on the cover.
We did the survey for four reasons: At a time when people are struggling to make ends meet, it's important to remember that OTC medicines save time and money. Second, to show at a time when the government and nanny-crats are cracking down on school lunches brought from home, seeking to make sugar a controlled substance and telling us that contraception has to be free but we can't have access to new cancer drugs and vaccines that still have control over what we can do to take of ourselves and families might be -- given the times -- a precious liberty. Third, that there is wisdom in the crowd. That the benefits of consumer empowerment outweigh the risks and that the risks themselves can be managed mostly by we-the-people by educating ourselves and each other. Finally, in the future turning more prescription medicines in OTC products is consistent with consumer-centered medicine, will save time and money and increase the number of people who take medicines in a routine and safe manner.
These things may be obvious. But too often they appear to be under assault. Alerting so-called opinion leaders, experts, etc., that Americans value the freedom they have value to buy cough and cold medicines when they are coughing and have cold symptoms may be alerting them to the obvious. But everything is obvious after the fact or when it's gone.
You can access the entire report, highlights and a press release on the CMPI website: http://www.cmpi.org
http://www.reuters.com/article/2012/02/14/roche-avastin-idUSL2E8DEIYC20120214
Counterfeits of Roche cancer drug found in US
* FDA investigating counterfeit Avastin
* Bogus Avastin label in French, says Roche not Genentech
* FDA has informed 19 medical practices about counterfeits
Feb 14 (Reuters) - Counterfeit versions of Roche's multi-billion cancer drug Avastin have been distributed in the United States, the Swiss drugmaker and its U.S. biotech unit Genentech said on Tuesday.
Roche was contacted about the bogus Avastin by a health authority outside the United States and was informed that the counterfeit drug in the United States came from another country, the company said but declined to divulge which country.
"We are working with the FDA and law enforcement to aid their evaluations, determine the source of the counterfeit drug, and prevent its further distribution," Roche and Genentech said in a statement. "The counterfeit product is not safe or effective and should not be used."
The U.S. Food and Drug Administration is taking the lead on the evaluation, a Genetech spokeswoman said.
Genentech said there is an ongoing investigation by national health authorities but could provide no further information at this time.
The FDA said it has sent letters to 19 medical practices informing them about counterfeit 400mg/16ml doses of Avastin.
The company does not yet know just how much counterfeit Avastin is out in the market. Avastin is given intravenously.
But there are several obvious differences in packaging and label that should allow doctors to easily spot the bogus drug.
Among them genuine Avastin, known chemically as bevacizumab, has Genentech on the label, which is all in English. The counterfeit says Roche and the label is in French.
Lot numbers of actual Avastin are comprised of six digits with no letters, while the counterfeit lot number begins with a letter. And the counterfeit bottles of Avastin are missing information on the label, such as "for intravenous use."
The Pink Sheet reports that the FDA wants to make a better case for increasing the use of accelerated approval, potentially as an alternative to implementing a new expedited approval mechanism.
In addition to saving the agency the inevitable headaches associated with implementing a new pathway, it also could quiet discussions about placing a new “Progressive” and/or “Exceptional” approval route into the agency toolbox. Draft legislation outlining both has been circulating among industry and congressional circles for several weeks.
The progressive approval concept would allow a drug to be marketed if evidence is submitted for a candidate that is likely to predict clinical benefit for a designated population and use. Exceptional approval would be allowed using an alternative showing if the data needed couldn’t be generated ethically or feasibly, according to the draft legislation.
On the January 15th edition of “BioCentury This Week” Center for Drug Evaluation and Research Director Janet Woodcock said that, while there are differing views on what progressive approval entails, the consensus is that no new approval pathway should lower the standards for safety and efficacy.
Woodcock also said accelerated approval is not realizing its full potential as a vehicle for qualifying drug candidates. She said it could be used more often and more consistently.
It would seem to be making the case that increased use of accelerated approval could be a viable alternative to instituting the two new approval schemes.
“[Accelerated approval has] been limited by its use, it’s not limited technically,” Woodcock said. “I think FDA could go a long way to [expanding the pathway’s use] with new guidance and new policies. I believe currently what’s codified in fast-track regulation is a little bit confusing about accelerated approval. So that could be clarified as well.”
Woodcock said more internal and external guidance on accelerated approval, such as provisions for the use of intermediate clinical endpoints, would help increase interest.
Woodcock said the concept of “staged approval” is feasible, but also potentially problematic.
“If you’re really going to have less evidence you've got to have some quid pro quo on the other side,” she said. “You can’t just toss it over the wall to the market and say go at it. And REMS doesn’t work in this situation because REMS is about a known safety problem.”
FDA also could speed up its approval of potentially breakthrough drugs by considering the best course of action early in the process, Woodcock said.
At the point a dramatic treatment effect is discovered, whether it is in a small population or any development phase, she suggested everyone “ought to all stop, take a deep breath and figure out how can we evaluate that drug as rapidly as possible.”
She said in some cases years could be cut off a drug’s development period if the larger treatment effect is verified.
“Even at that point, if it’s real, that’s a drug that offers something that no other drug’s offered before in that disease,” Woodcock said. “So you have to think how do we verify if that is real or not and then how do we evaluate the safety profile in the most efficient way possible?”
How, indeed.
Did somebody say “molecular diagnostics?” Did somebody say “personalized medicine?”
Von Eschenbach points to a troubling statistic that, according to the Tufts Center for the Study of Drug Development clinical trials from 2003-2006 were nearly 70% longer than those from 1999-2002. “Longer (and more complicated) trials have led to skyrocketing drug-development costs. High costs discourage investment in much-needed new therapies for conditions like obesity, diabetes and heart disease.”
Is this regulatory leadership? That’s debatable. Not according to a new California Biomedical Industry study that reports about 80% of life sciences CEOs surveyed don’t believe the FDA regulatory approval process "is the best in the world." Of equal import is that 81% of those surveyed believe that "within five years, another country could conceivably recreate the ecosystem that has made the U.S. the leading biomedical region in the world.” Investors talk with their feet.
Andy writes that, “Other countries such as Israel, Singapore and China are already preparing to leapfrog the U.S. for leadership of the global life-sciences industry.”
“Preparing” is one thing, doing it is another. But it is a real threat that we ignore at our own peril. As Sanofi CEO Chris Viehbacher said during his closing remarks at last year’s annual PhRMA meeting, “The question isn’t will our companies be successful? It’s will they continue to be successful in the United States?”
In January of 2010, I was part of a group of a group government regulators, health care policy experts, industry leaders, health economists, health care attorneys, patient advocates, and academics convened to study and offer new solutions to the hurdles to patient access and to develop high-impact global solutions.
(The report from this meeting, “Expediting Patient Access to New Medicines: A Call to Action,” was published in Drug Information Journal and can be found here.)
One of the ideas that discussed was for a new Asia-Pacific pan-regional regulatory agency that would provide centralized regulatory support outside of North America, Japan, and Europe. The goal would be to create an agency with sufficient resources and scale to accelerate drug approval in a region for which drugs are not usually designed. We suggested that the first embodiment of the idea could be an Asia-Pacific regulatory agency in Singapore that serves Australasia and Asia (ex-Japan). The creation of an additional new agency (similar in scale to the FDA and EMA) would continue to drive regulatory excellence but, more importantly, serve the needs of geographies that are underserved or dependent on guidance from the developed countries. This would encourage biopharmaceutical companies to invest in innovative medicines that may have a different regulatory pathway to approval, resulting in faster access to critical medicines in emerging markets.
Game on.
View PDF Here
http://tinyurl.com/83emomv
Andy is a visionary who transformed the National Cancer Institute and then went on to become fine FDA Commissioner under extremely difficult circumstances. He will be chairing MI's Project FDA and we wish him and MI the best of luck in this important endeavor!
As an historical footnote, I was chair of MI's 21st Century FDA Task Force from 2004-6. Peter and I wrote the Task Force report "Prescription for Progress: The Critical Path To Drug Development", which you can find here along with links to articles about Andy's participation in the report's release:
http://www.manhattan-institute.org/html/fda_task_1_members.htm
From today's edition of the Washington Examiner:
America needs more breakthrough “progressive” medicines
A recent global cancer conference was abuzz with discussion of a potential breakthrough therapy in the treatment of Alveolar Soft Part Sarcoma, a rare form of cancer afflicting only about 100 patients per year in the U.S.
If ASPS is not eliminated through surgery, it is always fatal. A new therapy for ASPS, called cediranib, was found in early testing to melt away the tumors in up to 70 percent of treated patients.
Yet there is no development pathway for FDA approval for such small populations of patients, so the world's next Gleevec lies on a shelf, with fingers crossed that years from now, after larger, longer clinical trials in higher-prevalence cancers are performed with cediranib, ASPS patients might get access through indirect means.
Simply put, at the FDA, there is no official process for the approval of a product developed to attack a condition afflicting just 100 patients. A Grand Canyon exists between reality and hope in our new age of personalized medicine.
Enter Sen. Kay Hagan, D- NC. As a member of the Senate Health, Education, Labor and Pensions Committee, she has proposed legislation known as the TREAT Act, which calls for FDA reform that would fast-track drugs that show promising early data in treating deadly diseases.
The bill is an acknowledgement of the failings of the 1990's accelerated approval regulations, which rely on "surrogate endpoints" for a clinical trial to represent and reflect the endpoint that is usually used for a drug's approval.
The result is an anemic armamentarium for our nation's number-one killer, and completely empty medicine chests for many rare cancer types.
The TREAT Act reforms the accelerated approval pathway to allow state-of-the-art clinical endpoints that are "reasonably likely to predict clinical benefit" as the basis for approval for life-threatening diseases.
For cancer, this change could allow a return to the notion of simple, universal measures such as significant tumor death, or delay in disease progression, as the basis for rapid release of new products to desperately ill patients. Additional data following confirmatory studies would then allow progression to full approval.
Safeguards are included in the bill to remove the product from the market should it not live up to its initial promise. Also, as a humanitarian gesture for micro-populations with deadly disease, there is the creation of an "Exceptional Approval" pathway.
This would authorize approvals when the usual data "cannot ethically, feasibly or practicably be generated." This pathway would be a game-changer for U.S. rare disease populations of extraordinarily small numbers.
Thanks to Hagan, there can be a new way forward for development of therapies not just for rare cancers, but for thousands of life-threatening rare diseases where there are no realistic opportunities for drug development. Such reforms go beyond helping only the forgotten orphans.
By fostering innovation in new arenas of drug development, jobs are created and businesses prosper, and innovation accelerates the boundaries of medical knowledge and patient possibilities.
Now is the time to embrace a 21st century FDA -- and progressive approvals is a good place to start.
Peter Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest. Dr. Mark Thornton, a former FDA Medical Officer, is president of the National Organization Against Rare Cancers and is employed in the biotechnology industry.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
