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Single-payer health care unworkable, too costly
In an attempt to halt Bernie Sanders’ rise in the polls, Hillary Clinton is waging a campaign against his single-payer health plan. Remarkably, one of Clinton’s main criticisms is that Sanders’ scheme would undermine the cause of federally controlled health care by giving too much power to the states. Yes, we must be in an election year.
As Clinton has put it, Sanders “wants to roll Medicare, Medicaid, the Children’s Health Insurance Program, the Affordable Care Act program, and private health insurance into a national system and turn it over to the states to administer.”
The real problem with a single-payer system, however, is much simpler: The approach has failed everywhere it has been tried — from Europe to Canada to Sanders’ own state of Vermont. In almost every instance, government-run health care has suppressed medical innovation and made it harder for patients to get the treatment they need at a price they can afford.
Both candidates ought to be discussing practical ways to fix our health system’s most serious flaw — too much government intervention. Instead, they’re quibbling over the many faults of a single-payer program that would dramatically lower the quality of care for all Americans.
While he has yet to provide many serious details, Sanders’ proposal creates a single-payer health program that would “cover the entire continuum of health care,” from inpatient care to hearing, vision, and oral health.
Sanders tends to frame his plan as a way to “join every other major industrialized nation on Earth and guarantee health care to all citizens.” But one need only look at these other nations to understand why Sanders’ vision is a step in the wrong direction. As anyone who has ever stood in line at the Department of Motor Vehicles can understand, government-run systems are invariably wracked by inefficiencies. When it comes to health care, one size doesn’t fit all.
For instance, Canadian patients hoping to see a specialist physician can expect to wait more than 18 weeks. An MRI scan in that country takes more than 10 weeks. Waiting times have grown so long in Sweden’s single-payer system that one in 10 citizens has opted for private coverage.
In order to contain health costs, Sanders promises to “stand up to drug companies and negotiate fair prices for the American people.” But again, the disastrous effects of drug price controls have been clearly demonstrated throughout Europe.
To take one example, the United Kingdom’s National Health Service (NHS) consistently denies patients access to the most up-to-date treatments if they are deemed too expensive by regulators. These decisions often lead to avoidable suffering for those in need of care. Last summer, in fact, British health administrators refused to pay for a breakthrough ovarian cancer drug until patients had undergone three rounds of chemotherapy.
Drug price controls also come at the expense of medical innovation, as they weaken the incentive for pharmaceutical firms to invest in research and development. In the 1970s, four European countries invented 55 percent of the world’s new drugs. Decades of increasing price controls in Europe pushed drug development efforts — representing hundreds of billions of dollars of investment and economic activity — to the United States. Between 2000 and 2010, those four countries accounted for a third of pharmaceutical innovation, while the U.S. share rose to 57 percent.
The nonpartisan National Bureau of Economic Research cautions that “cutting \[drug\] prices by 40 to 50 percent in the U.S. will lead to between 30 to 60 percent fewer R&D projects being undertaken.” Less research means fewer new medicines and fewer lives saved.
Then there’s the issue of cost. Sanders estimates his plan will cost the country a whopping $1.38 trillion a year — money he intends to raise through a variety of tax hikes. As Sanders knows, this is precisely the strategy that failed in his home state in 2014.
Vermont Gov. Peter Shumlin had planned to pay for a statewide single-payer system through significant tax increases. After realizing how expensive the program would be, Shumlin abandoned it, admitting that “the potential economic disruption and risks would be too great to small businesses, working families, and the state’s economy.”
Even in liberal Vermont, 64 percent of residents supported Shumlin’s conclusion that a government-run health system comes at too high a price. Yet, single-payer health care now dominates the conversation between the leading Democratic candidates. As the policy has no history of success and poses immense risk to our health sector, what is there to debate?
Peter J. Pitts is president of the Center for Medicine in the Public Interest and a former Food and Drug Administration associate commissioner. Read More & Comment...
Peter Bach is the Donald Trump of health care policy. I am not referring to his hair or hand size. No, Bach – like the Donald – is a master of enchanting his followers with outrageous statements that scapegoat easy targets and unfairly attack them for acts of greed that you are actually guilty of committing. And it helps to have megaphones in the media who agree with you to promote your false position. (Bach’s newest mouthpiece is Gardiner Harris, who has returned to the NY Times to write fiction about the pharmaceutical industry.)
The most recent manifestation of Bach’s Trumpism is a ‘study’ he published in the British Medical Journal (I am assuming his co-authors were either blackmailed or brainwashed) claiming that US drug companies systematically increase the dose size of biologic injections for cancer and autoimmune disease even though smaller amounts are used for no other reason than profit. Bach and company assert that firms should produce smaller vials of medicines because it would save the US health system $3 billion a year.
But as with most of what Bach does, the BMJ article is a pseudo-economic exercise shorn of relevant facts that undermine his central argument. In fact, the issue of what to do with remaining medicine is more complex.
1. Most medicines – whether they are in injectable or pill form – come in a fixed number of doses. Dose sizes are based on averages of weight, age, severity of disease. They are NOT produced in the amount just right for you and me.
2. Dose size is almost always determined by what the FDA establishes is the safest and most effective dose for an average patient population. Quantity is not driven by profit. Rather, one of the biggest reasons drugs in development do not make it to market is the wrong dose size. Even today, lots of clinical trials flop because companies because companies use the wrong dose in studies to measure clinical benefit. Failure to select an ‘optimal’ dose to show effectiveness is the single reason drugs are either delayed or rejected by the FDA.
3. To minimize risk, developers are often evaluating doses near the maximum tolerated levels. And more to the point about drug waste, companies limit the number of dose sizes tested in order to avoid testing doses that don’t work and then force the company to do every trial over again.
4. Companies must also follow FDA and USP guidelines that govern how much of a drug can be in a vial. The FDA has urged companies to move away from a multiple number of smaller vials to a larger single vial.
5. In addition, many injectable products are now made by generic manufacturers. The increase in the frequency and number of shortages for such drugs is due to a combination of increased production and formulation costs and government fixed prices. The incentive for additional dosage amounts is therefore limited or non-existent.
Since Bach and co-authors are intent on accusing drug companies of simply going with larger doses to rake in profits, it is not surprising that they ignored these important regulatory and scientific factors.
Nor is it surprising that Bach and friends note – incorrectly -- that many cancer drug doses are based on body surface or body weight. In an exclusive New York Times interview timed to the release of their ‘study Bach says sarcastically. “Drug companies are quietly making billions forcing little old ladies to buy enough medicine to treat football players, and regulators have completely missed it,” said Dr. Peter B. Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering and a co-author of the study. “If we’re ever going to start saving money in health care, this is an obvious place to cut.”
Bach increasingly makes statements that support his case and are quotable, that are also false or without substance. (He recently claimed that new drugs that eradicated Hepatitis C virus were NOT a cure.) Similarly, in asserting that drug companies are endangering frail elderly females by giving them enough of a drug to treat a defensive end, Bach fails to mention there is an absence of scientific evidence that such dosing is safer or more effective than flat fixed dosing. The implementation of so-called genotyping and phenotyping strategies, and therapeutic drug monitoring, may probably be of more clinical value.
He also ignores how hospitals and oncologists can benefit from ordering bigger dose sizes. Peter Ubel notes: “Oncologists purchase intravenous chemotherapy from pharmacies. Patients then receive these drugs in the oncologists’ offices, with outpatient chemotherapy being an increasingly common setting for cancer care. The oncologists then bill patients’ insurance companies for the treatments, including billing the payer for the cost of the chemotherapy PLUS a percentage based mark-up.
Medicare, for example, receives bills from oncologists that charge 106% of the cost of the chemotherapy. Many private insurers pay even larger mark-ups, especially from oncology practices that dominate their local markets and thus have pricing leverage.
This “buy and bill” practice creates an incentive for oncologists to prescribe expensive treatments. After all, a $6 mark-up on a $100 treatment doesn’t do much for the bottom line. But that $600 mark-up on a $10,000 treatment? Give that treatment to enough patients and we’ll soon be talking about real money.”
Indeed, it is ironic that Bach and one of his co-authors, Leonard Saltz, became crypto famous by getting Sanofi to cut the price of a cancer drug by 50 percent and writing about it a New York Times op-ed piece. The duo asserted that they wouldn’t prescribe the drug because it cost twice as much as Genentech’s Avastin (bevacizumab), a competing biologic drug with similar expected clinical outcomes for colorectal cancer patients. In response, Sanofi said they would reduce the price of the drug by 50 percent.
In fact, doctors and prescribing hospitals benefited hugely from Sanofi’s pricing move, while payers and patients did not. Zaltrap was sold in a dose twice as large as Avastin, thus the price discrepancy. Further, Sanofi didn’t cut the price of Zaltrap; it gave Memorial Sloan a 50 percent rebate. The price charged to patients remained the same. Which meant that MSKCC raked in even more dough. As an article in Health Affairs noted at the time, “Meanwhile, in the near term, physicians and hospitals will likely enjoy additional revenue opportunities from ziv-aflibercept use. the spread may be considerable: equal to $250 per treatment dose (insurer + patient reimbursement ($750) – discounted acquisition cost ($500)) and for 340B eligible purchases, $450 per treatment dose (insurer + patient reimbursement ($750) – discounted acquisition cost ($300)). Additional revenues may incentivize physicians and hospitals to favor ziv-aflibercept over bevacizumab to treat colorectal cancer among Medicare eligible patients, despite the treatments having equivalent expected clinical outcomes. The strength of the incentive is based on comparing the magnitude of the spread obtained with the use of Zaltrap to that obtained with Avastin.
Finally, hospitals are profiting from the deep discounts they receive on injectable drugs under the previously mentioned 340 B program, a federal policy under which, “hospital outpatient departments can purchase oncology drugs using the deepest discounts available”.
Adam Fein has skewered the 340 B program on a number of occasions. In one article he discussed a study the concluded that some 340B hospitals simply pocket the extra profits. The New England Journal of Medicine paper examined the behavior of “charitable hospitals.” As this summary notes:
“Only 42 percent notified patients of their eligibility for charity care before attempting to collect medical bills and only 29 percent had begun charging uninsured and under-insured patients rates equivalent to private insurance and Medicare rather than standard, higher charge master rates.”
Indeed, another pricing expert noted that the use of drugs for the poor as a profit center is part of the broadere focus of hospitals, PBMs and insurers on generating “primary revenue being from the buying and reselling of drugs”.
That assertion was made by Peter Bach.
So what about drug waste as if the facts mattered?
Many hospitals have robust programs consistent with FDA and USP guidelines to use to make up from lost 5 % of total anticancer drug expenditure The economic loss due to their waste equaled 4.8% of the annual drug expenditure. In particular, hospitals use dose rounding to generate significant cost savings by eliminating drug waste.
So Bach’s effort to blame drug companies for waste generated greed is, like many of his recent attacks on drug prices, largely free of facts and at odds with the reality.
Read More & Comment...
FDA presenters included agency point-man Doug Throckmorton (Deputy Director for Regulatory Programs, CDER), Janet Woodcock (Director, CDER), Sharon Hertz (Division Director, Division of Anesthesiology, Analgesia and Addiction Products), Gerald Dal Pan (Director, Office of Surveillance and Epidemiology) – and newly confirmed FDA Commissioner Rob Califf.
Califf was there at the beginning of the meeting (expected) and stayed through the entire length of the day-long affair (unexpected). An important signal that he intends to be a hands-on leader.
I was chosen to speak during the open public comment part of the hearing, and spoke about using real-world information to provide providers and patients with information beyond the limited world of pivotal trials. Here are my brief remarks:
Former Canadian Prime Minister Pierre Trudeau once said, “There's no place for the state in the bedrooms of the nation.“ But what’s the appropriate place for the state in examination rooms, pharmacies and medicine chests – particularly for opioids? There is no such thing as a medicine that is 100% abuse-proof. The only abuse-proof medicine is one that is never prescribed – and for the tens of millions of Americans suffering from chronic pain that isn’t a viable option.
Advancing the manufacturing science of abuse deterrence is an important step in the right direction. According to the Journal of Pain, in a real-world study, abuse by snorting, smoking, and injecting prescription opioids declined by 66% after the reformulation of a drug with abuse deterrent properties. And the New England Journal of Medicine reported that a new formulation decreased abuse from 35.6% of respondents to 12.8% in 21 months.
But cutting the Gordian Knot of abuse means more than advancing the science of abuse deterrence. It means working with the providers of Continuing Medical Education to develop better curricula. It means more targeted Risk Evaluation and Mitigation Strategies. It means enhanced and validated reporting tools for post-marketing surveillance. And it means using real world data to provide real world advice. It means using that data for better social science tools that can assist prescribers in determining which patients are likely to abuse.
“Abuse deterrence” isn’t just a formulation question – it’s a systems question.
What about the issues surrounding opioid misuse – at present the poor public health stepchild of abuse? And how can better physician education defer or deter the prevalent “opioids first” prescribing philosophy of many practitioners?
In the U.S., the use of opioids as first-line treatment for chronic pain conditions follows neither label indications or guideline recommendations. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy.
Payers often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options – along with new abuse-deterrent opioid formulations. The result is a gateway to abuse and addiction.
Various pieces of state legislation are trying to correct this, but there has to be a better way.
The FDA can play an important role in working to develop and share (with a broad constituency) validated tools for physicians to use in determining which patients may be more prone to slide into abuse so they can choose their therapeutic recommendations more precisely.
The FDA has announced labeling changes and post-market study requirements for opioids, and the agency has signaled interest in using real world outcomes data to amend and update labeling. That’s not regulatory mission creep; it’s the appropriate application of the agency’s Safe Use of Drugs initiative. The way you make a drug “safer” is to ensure that it is prescribed to the right patient and used in the proper manner.
A logical next step is to utilize that real world data to amend product-specific abuse-deterrent labeling to indicate lessons learned outside of the rarified world of the randomized clinical trial environment to assist physicians in using the right product for the right patient. Such changes mark important steps in highlighting the value of individualized patient pain-management programs.
Abuse-deterrent technologies are an important step in the right direction. They are part of the solution, but they’re not the whole solution.
It’s important to remember that the vast majority of people who use opioids do so legally and safely. In fact, government statistics show that 78.5% of those who abuse prescription pain medication did not obtain the drugs from a doctor in the first place.
Abuse deterrence is a worthy goal and will only evolve when all the players work together in a more regular and synchronistic fashion. As the Japanese proverb goes, “Don’t fix the blame, fix the problem.” Read More & Comment...
As BioCentury reports, PhRMA EVP and General Counsel Mit Spears said that while the Duke-Margolis Center paper does a good job of making the public health case for improving off-label communications policies, it “dances around” the single most important issue: how FDA defines the “truthful and non-misleading” standard the courts have set for corporate free speech.
“I don’t think you can resolve the issue without resolving the question of what constitutes truthful and non-misleading information,” Spears said. “That’s up to FDA or the courts to decide, and we think it is much better if it is FDA.”
He told BioCentury there is a danger that courts could back FDA into a corner, mandating communications policies that comply with the First Amendment to the U.S. Constitution, but that don’t take all of the nuances of public health into consideration.
Spears and PhRMA did not participate in the Duke-Margolis Center working group.
Speaking as a member of the Duke-Margolis working group, I could not agree more. As the BioCentury article reports, Speaking at the Duke-Margolis Center meeting, Peter Pitts, president of the Center for Medicine in the Public Interest, also warned that the courts or Congress could take the off-label policy debate in directions that could be bad for public health. “Unless FDA steps up to the plate to lead this conversation, but also looks to outside advisors to help it formulate its viewpoints, we are all going to be sucked into a very unpleasant vortex,” he said.
The complete BioCentury article, “Off-Label Options,” can be found here.
Read More & Comment...
Today is Rare Disease Day. You probably missed the media coverage because there was none.
That will make Steve Pearson, the founder of the Institute for Clinical and Economic Review(www.ICER.org) – the so-called drug pricing watchdog – very happy.
That’s because Dr. Pearson believes that public awareness of rare diseases leads us to invest in more and more treatments for even more rare diseases that – in his opinion – will make health care spending ‘unsustainable.’
Or has he put it in an article entitled, “Which Orphans Will Find a Home? The Rule of Rescue in Resource Allocation for Rare Diseases,” there is no apparent obligation to rescue identifiable
rare disease patients based on a duty of rescue within personal morality.” Rather, he claims that while the impulse to save people with rare diseases is appealing, it is more ethical to restrain that policy because it forces us to spend more money on health care at a time of “permanent” resource scarcity.
To put it bluntly, Pearson believes groups like ICER can use evidence-based policies to decide who shall live and die, who shall suffer and who shall thrive.
Let’s set aside the specious assertion that we are running out of money to spend on health care. Like many Malthusians, the underlying assumption shaping Pearson’s and ICER’s mission is the believe that there is a moral imperative to spend less on health care. And Pearson, like his Club of Rome predecessors, is gripped by the belief that we can’t take care of all these sick, disabled people at any price otherwise we will have no money for anything else!
Here is Pearson with his pessimism in full flower:
“Increasing numbers of expensive orphan drugs are expected to come to market. In addition,
advances in pharmacogenetics will soon be able to separate many common diseases, such as hypertension, arthritis, cancer, and diabetes, into numerous small and distinct subpopulations of patients with specific genetic profiles. This movement toward “personalized medicine” will
produce increasing numbers of drugs that have been developed to treat small, identifiable patient groups.
Instead of a new blockbuster drug to treat millions with hypertension, new targeted therapies will treat only those few thousand with a particular genetic makeup. As the eligible patient
populations decrease in size, the arguments for accepting higher prices per treatment will turn manageable overall costs into unsustainable ones. As the eligible patient populations decrease in size, the arguments for accepting higher prices per treatment will turn manageable
overall costs into unsustainable ones.”
If everyone has a rare disease, there will be fewer people with a one size fits all diagnosis. So the number of people with an illness will not increase (holding population growth constant.) That mathematical fact eludes Pearson who insists that all these new orphan drugs will crowd out spending for other health care services.
Similarly, claims of budgetary Armageddon have been overhyped by Pearson. Between 2007 and 2014,orphan drugs have increased as a percentage of spending on drugs (from about 2 percent to 4 percent in Europe and 5 percent to 8 percent in the United States ) even as the percentage spent on drugs has remained the same.
What about the impact of the ICER like restrictions Pearson wants to impose? Indeed, “orphan drugs currently have more coverage restrictions than non-orphan drugs in the United States, United Kingdom, and Netherlands.” And the United States is less restrictive than other countries.
The rationing of orphan drugs does increase suffering and cost lives. Frank Lichtenberg concludes that between 1999-2007, new orphan drug approvals reduced life years lost to rare disease by 4.2 percent a year. (Without these new drugs, the number of deaths would have climbed by about 1 percent a year)
In France, which took longer to pay for orphan drugs and paid for fewer relative to the US, the number of deaths declined by 1.8 percent.
This loss of life is, according to Pearson, the price we have to pay for avoiding scarcity.
And he believes that a “bright line between what constitutes a fair claim on health benefits and what does not will be difficult to draw.”
Indeed, ICER sets the cut off point for the rationing required to avoid ‘scarcity.’ It has determined exact numbers of people who will be denied access to a growing array of new medicines.
The media has hailed ICER’s effort to set drug prices. But these limits are determined by how valuable ICER thinks a new drug is and by the amount ICER believes should be spent on each new drug a year. This has led ICER to recommend limits on the use of new medicines – even when they are price at levels that would make their development economically impossible – that ensures some people will suffer and die in order to stick to an arbitrary budget threshold. Indeed, ICER assumes that a new drug – even a cure – is of lower value to society if it increases cost beyond a certain limit.
Indeed, Pearson’s bright line is drawn based on the number of people that can be treated and little more. He says that paying $200K for a rare orphan drug is reasonable if it only helps a small number of patients. But he concludes that people with the toughest cancers to treat, for whom a small average survival benefit is a breakthrough, are not worth treating. He claims lung cancer patients shouldn’t stir our compassion because our feelings are simply a response to a patient led PR campaign. Pearson states: “Although nonsmall cell lung cancer is technically a rare disease, 60,000 patients are diagnosed with the illness each year in the United States. The treatment costs for each individual patient average approximately $80,000, which translates into an expenditure of $4.8 billion dollars per year. “
Pearson – and ICER – deliberately ignore the fact that average overall survival means very little at time when we can match people to combinations of treatments based on our understanding of how tumors thrive and progress. But even if they did incorporate it, the cumulative spending on lung cancer patients -- $4.8 billion – is about $3.9 billion more than ICER wants to spend on each new drug. New immunotherapy drugs double the percent of patients living a year or more with lung cancer. To Pearson, that’s bad news indeed.
He, like so many social engineers before him, have assumed that keeping more people alive longer will hurt society as a whole. But incremental and cumulative advances in medicine, as they are diffused and adopted, leads to greater gains in well-being and economic growth.
It is precisely our moral sense to save lives in immediate danger and at any expense that sustains humanity and economic progress. We need more orphan drugs because we gain when more of us enjoy life and live longer.
Pearson and his ICER are a threat to that prosperity and the remarkable advances in medicine that Rare Disease Day celebrates. Do we really want to allow someone who belittles such acts of awareness to determine who gets what medicines at what price??
Read More & Comment...
CVS’ ballyhoo that they “reduced the rate of drug spending” in 2015 is barely half the story. And as my grandmother used to say, “A half-truth is a whole lie.”
CVS, which manages drug benefit plans for more than 75 million Americans, kept costs down in 2015 by negotiating discounts from big manufacturers and carefully managing its list of covered drugs – and by denying patients the medicines prescribed by their physicians.
Yes, they decreased RX expenses but they haven’t any clue what happened to overall healthcare costs, out of pocket costs and, more importantly, patient outcomes.
In a nutshell, CVS removed some drugs from formularies and limited access to others – and asthmatics are in the emergency room. That’s not a public health victory. Read More & Comment...
At a crucial moment in American (indeed global) healthcare, he brings a vision for FDA as an innovation accelerator, steward of post-market safety, guarantor of quality, and first among equals when it comes to leading the agency’s intramural partnerships on a plethora of issues with its many constituencies. Perhaps most importantly, is Califf's role as agenda-setter and cheer leader at an agency comprised of highly educated and dedicated (and career) public servants.
The past is prologue. Read More & Comment...
Now policymakers want to make sure you don't have to be an ex-President to get the best treatment immediately:
Georgia Bill Inspired by Jimmy Carter's Cancer Treatment
Georgia lawmakers have approved a bill inspired by former President Jimmy Carter's cancer treatment.
The bill prevents insurance companies from limiting coverage of drugs for stage 4 cancer patients.
Carter, now 91, announced in August that he had been diagnosed with skin cancer that had spread to his brain and would begin receiving doses of Keytruda. The newly approved drug helps his immune system seek out cancer cells appearing in his body.
Carter said in December that a scan of his brain detected no sign of cancer cells. He has continued treatment.
Republican Rep. Mike Cheokas from Americus is the bill's sponsor. Cheokas said no one facing cancer that has spread should have medical treatment options limited by insurance providers.
The bill now goes to the state Senate for review.
In introducing the bill, Representative Cheokas said something that should be a campaign slogan nation-wide: "Cancer is a non-partisan issue. It affects young and old, black and white, rich or poor; It really doesn't matter."
Read More & Comment...
But the real heroes in the ‘battle’ to reduce what are always referred to as skyrocketing drug costs are people like Nicole who are denied access to new medicines in order to pad the profits of CVS and other PBMs:
Nichole, a 25-year-old living with Hepatitis C, was desperate when she reached out to WBZ-TV.
“A week ago, I didn’t feel any hope,” she told the I-Team.
She had been struggling with the disease since she was abducted four years ago. The fatigue and jaundice, plus the stigma made it hard to get on with her life.
Making matters worse, the man who victimized her had received a life-saving cure in prison.
Nichole was left only with multiple denial letters from her insurance company, Tufts Health Plan.
“Aside from the physical, emotionally, this has been horrible,” she told WBZ in January.
Nichole’s doctor prescribed it saying she was a perfect candidate. It would help rid her of the disease and move on. However, a full treatment of Harvoni is priced at a whopping $84,000. That’s $1,000 per pill. Tufts Health Plan denied Nichole coverage of the drug, saying she isn’t sick enough yet. “The insurance company wants me to be in Stage 3 liver scarring,” she said.
Let the record show that this denial comes from CVS, the hero of drug pricing critics. And the rationale for rationing Nicole is courtesy of our friends at the Institute for Clinical and Economic Review. These drug price watchdogs, as their acolytes in the media has hailed ICER, has recommended that HCV patients like Nicole be denied cures until there “is some evidence of liver fibrosis.” More on this media anointed (as well as health plan and Enron billionaire funded) arbiter of price and the value of a human life in a future post.
And don’t forget that CVS has an exclusive deal with Gliead to make it the only HCV drug on their formulary. But even then, you have to fail first or get liver damage to try another drug.
Nicole is one of the lucky ones. According to Camilla Graham, MD, assistant professor of medicine at Beth Israel Deaconess Medical Center in Boston. Every single Viekira Pak scrip she has written for her Medicaid patients has been denied. “Things aren't going so well, and Massachusetts, I will say, has the best access of any state. Our Medicaid doesn't have ridiculous restrictions,” she says. “I'm calling them restrictions, but it's really rationing. We're seeing rationing of care for hepatitis C like I've never seen in U.S. medicine.”
CVS’ chief medical officer, Troyen Brennan, said that without Sovaldi being introduced, the 11.8% growth might have been about 10%, and that this year’s spending growth would have remained at about 5%.
But wasn’t Solvadi going to increase premiums by 30 percent? Brennan co-authored a piece in JAMA in which he asserted. “ The simple math is that treatment of patients with HCV could add $200 to $300 per year to every insured American's health insurance premium for each of the next 5 years,"
That’s BS obviously. Even worse, it was BS used to justify rationing drugs and cutting exclusive deals with drug companies so that sick patients would have to beg for cure.
Meanwhile, the “fine-tuning” as Matt Herper happily describes is more like a blitzkrieg against access. As Adam Fein dryly notes:
Express Scripts has 66 products on its 2015 formulary exclusion list, compared with 48 in 2014. CVS Caremark’s 2015 list has 95 products, including 72 carryovers from the 2014 edition. Nostalgic readers will recall that CVS Caremark removed a mere 34 drugs from its 2012 standard national formulary. I guess there ain't no valley low enough, either.
Adam’s right. CVS and other PBMs haven’t reach their low point in limiting access, cutting deals and using ICER as a price fixing front in order to maximize the spread between the net cost of a drug (often up to 40 percent of average wholesale price) and how much they force patients to pay out of pocket for medicines that are right for them.
As Stacy Trooskin, MD, PhD, assistant professor in the division of infectious diseases and HIV medicine at Drexel University College of Medicine in Philadelphia points out: “I get a little bit concerned when we have exclusivity deals and none of these price cuts that the payer is receiving from the pharmaceutical company translate to ease of access.”
The decline in drug costs is a result of the increased success of PBMs extracting rebates and denying access. A Credit Suisse analyst report found that: “For 2014, our 20 company universe has shown net US drug sales of $202bn and reported total rebates of $98bn. We conclude that in 2014 US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures. “
Which means that 2015 was a great year for PBMs because it was worse for patients.
Read More & Comment...
The most important outcomes are steps that are intended to improve FDA’s ability to recruit, hire and retain scientific staff, measures to improve the agency’s financial transparency and accountability, and extensions of ongoing efforts to integrate patient perspectives and real-world data into regulatory decision making.
Completion of the goals letter, expected in March, and review by HHS and the White House over the summer, will mark the end of the first phase of the PDUFA reauthorization process. But it only will launch the start of the much more arduous portion of the PDUFA reauthorization journey: congressional approval.
I. Fixing HR
FDA’s ability to meet user fee review goals, and to go beyond them by implementing new regulatory ideas and proactively supporting product development, depends almost entirely on its ability to recruit, retain and develop talented and dedicated staff.
At the start of PDUFA VI negotiations, PhRMA and BIO told FDA that industry would not support increases in user fees to hire new staff unless CDER demonstrated that it had put procedures in place that would fill staffing holes and provide confidence it could hire to fill new positions funded by PDUFA VI. According to industry negotiators, CDER and FDA have met the challenge, in part by taking some steps that are common in the private sector, such as hiring external head hunters.
Unlike previous user fee agreements, which paid for FTEs even if they were never hired, the agency will only receive the additional money if it meets recruitment and retention goals. FDA has also agreed to hire an external organization to assess and continuously evaluate its hiring and retention efforts.
Other nuts-and-bolts activities covered in PDUFA VI include improving the reliability of the electronic filing process for new drug applications, steps to improve the management of meetings between FDA and sponsors, and revamping a formula that is used to increase user fee payments based on estimated workload.
II. Breakthroughs and Biomarkers
Some of the new hires will work on improving FDA’s review of products that combine drugs and devices, and on the breakthrough therapies program. The breakthrough process is resource-intensive, and the largest allocation of new staff in PDUFA VI, about 60 employees, will be dedicated to breakthrough reviews. PDUFA VI will also include additional money and mandates for FDA to review drug development tools, including surrogate endpoints, biomarkers and patient-reported outcomes (PROs).
Alas. industry dropped attempts to establish review time goals for biomarker qualification.
Advancing FDA’s patient-focused drug development (PFDD) initiative is another priority for patient groups as well as for industry and FDA. FDA has already started expanding PFDD by encouraging patient groups to hold their own meetings modeled on meetings the agency has held. PDUFA VI will include a series of guidance documents that are intended to lead to PFDD version 2.0, which could include establishing standards for conducting and analyzing patient-preference research, and taking steps to formally integrate patient preferences into regulatory decisions.
FDA created structured benefit-risk frameworks during PDUFA V, and will expand their use in PDUFA VI.
Advancing the use of real-world evidence to make regulatory decisions will be another major emphasis of PDUFA VI. This will include enhancing the Sentinel Initiative, a system that allows investigators to monitor and query electronic medical records, health claims databases and other sources. Projects under consideration for Sentinel include monitoring the safety of biosimilars, and broadening its focus from safety to efficacy.
Biopharmaceutical companies are looking to PDUFA VI to open legal avenues to communicating with payers and possibly other parties about real-world data on off-label uses of approved drugs.
Finalization of the draft PDUFA VI goals letter will set in motion a series of reviews by HHS and the White House Office of Management and Budget that are slated to be completed by September. Following publication of the draft agreement in September, and a final public meeting in October or November, the deal should be formally submitted to Congress in mid-January.
PDUFA VI AT A GLANCE
* Improve FDA recruitment, hiring, retention: Implement HR improvements, hire outside HR contractors, contract for external analysis and monitoring of progress
* Funding for about 200 additional full-time employees (FTEs): Funding contingent on FDA meeting recruitment, retention goals
* Increased funding for breakthrough reviews: Largest portion of new FTEs
* Modification of the “workload adjustor” formula used to increase user fee payments based on anticipated submissions: Annual user fee increases expected to be smaller; FDA to gain more predictable funding
* Patient-focused drug development 2.0: Issue a series of new guidance documents on patient-focused drug development
* Research on the integration of real-world evidence into product reviews: Expand Sentinel Initiative, a system for postmarket monitoring and querying of electronic health records, insurance claims and other records to track medical product safety; Implement other efforts to use real-world evidence to study and communicate about safety and efficacy
* Increased funding for review of drug development tools: Add resources to qualify surrogate endpoints, biomarkers, patient-reported outcomes; Expand use of benefit-risk framework to guide drug development activities; Enhance FDA capacity to analyze innovative clinical trial designs
* Increased transparency regarding spending PDUFA funds
* Information technology improvements: Increase reliability of the electronic submissions system, upgrade CDER's IT system Read More & Comment...
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.” Read More & Comment...
Take this story from Minneapolis.
A major company has rolled back the price of a potentially life-saving prescription drug after a KARE 11 News investigation.
But the decision has some people asking how often we’re being overcharged on other medicines.
It started with Curt Burshem.
Back in November he told us CVS Caremark had jacked up the price for a prescription drug a family member needed for a kidney disorder.
Curt Burshem discovered that CVS was overcharging him on prescription drugs.
"When I see a company doing this crap, it makes me insane,” he said.
But, now, CVS has reversed the price high.
"Justice had been served,” Curt told us.
When Curt originally went to the CVS pharmacy in Maple Grove last Spring, the initial 30-day supply cost about $.87 per pill.
But when he followed his insurance company’s advice and ordered a 90-day supply through the mail, CVS Caremark increased the price to more than $6 a pill.
After KARE 11 called CVS they rolled the price back and gave Curt a refund.
Which raises the question: If transparency proponents were intellectually honest (some are, most are not) they would demand the same openness from every health care institution that shapes access to and the price of medicines.
Will PBMs and insurers reveal how they move from drugs that they acquire at 40-60 percent below pharmacy retail prices to charging consumers 30 percent of that retail price?
Will PBMs and insurers reveal how and why they decide when their customers are forced to fail first on medicines?
We need to know. They claim drug costs are climbing at an unsustainable rate. That doesn’t square with data since 2000, spending on drugs has remained at 9-10 percent or HHS projections that overall drugs will remain at about 9 percent of total health spending through 2030. So why are copays and co-insurance rates increasing??
Will hospitals reveal how they go from drugs acquired at the same rate to charging up to 700 percent of retail prices? And while they are at it, will they explain why charges for hospital care increased faster than drugs, even as the use of these new medicines reduce hospital costs? Why has hospital spending increased 6 times faster than drug spending between 2010-2013?
If I am a pharmaceutical company, I’d be for transparency for everyone. I’d show them mine, if they showed theirs. Let’s have the Full Monty for all. Read More & Comment...
In a cramped Mumbai paediatric ward, third-year pharmacology student Nitin Shinde opens the boy's file and notes the vaccine, his age and the doctor's diagnosis of a skin infection. That information is later logged into a computer programme linked to a national database, part of India's fledgling efforts to track, analyse and ultimately warn patients about unknown side effects of drugs on the market.
India's six-year-old pharmacovigilance programme, which collects and submits suspected adverse drug reactions to a World Health Organisation (WHO) database, is key to improving drug safety in a country where medicine consumption is high, experts say.
But insufficient staff and equipment, and a lack of awareness among medical professionals mean many potentially dangerous drug reactions go unrecorded, hospital personnel across India told Reuters.
Gaps in the system mean the government has less data to determine whether drugs might have harmful side effects. Also, relatively little information flows from one of the world's largest pharmaceutical markets to the WHO database of over 12 million suspected adverse drug reactions.
"In a country of 1 billion people consuming so much medicine, obviously safety is a concern," said G. Parthasarathi, dean of the pharmacy school at JSS University in Mysore, adding the pharmacovigilance programme is still gaining traction. "We've made a good start," he said.
Last year, India contributed 2 percent of the 2.1 million suspected reactions added to VigiBase, the WHO's global database. China, with a comparable population, contributed 8 percent.
Indian health officials say the monitoring programme is a "high priority" and a $14.5 million annual budget is sufficient.
"We are going to develop a better pharmacovigilance system in India in due course," said G.N. Singh, India's drug controller. "Patient health will be assured."
Regarding doctors' lack of engagement, "the culture of reporting is improving," said V. Kalaiselvan, principal scientific officer at the Indian Pharmacopoeia Commission.
The full Reuters article can be found here.
Read More & Comment...
Much of what passes for journalism or commentary about the biotechnology/pharmaceutical industry is click driven hate mongering. Want to write about drug companies. Start with this theme: Everything drug companies do is disgusting. Nothing they do is beyond reproach. Use h one example of unseemly behavior and claim every company does the same thing. Add some anger and sarcasm.
Pharma sucks. Ha-ha.
Press send or post.
Here’s some recent examples in order (mostly) of idiotic magnitude:
Here’s what White House Chief of Staff Denis McDonough said in the wake of a Super Bowl commercial to raise awareness of opioid-induced constipation run two companies marketing a drug to treat it: “Next year, how about fewer ads that fuel opioid addiction and more on access to treatment.” commercialized and misused pharmaceutical knowledge,” he told a United Nations agency.
Apparently McDonough never got the memo that people – including millions of cancer patients and individuals with digestive tract paralysis who safely use opioid based drugs to control searing pain – should have the same right to poop as White House staffers.
Bill Maher tweeted (and this is evidence of why humor should be left to humorists) “Was that really an ad for junkies who can't shit? America, I luv ya but I just can't keep up.”
In between the harsh sarcasm of the White House and Maher’s tweet is the much needed gap created by Samantha Allen of the Daily Beast:
Martin Shkreli Is Just One of Many Pharma A-Holes
Nancy Retzlaff is not Martin Shkreli. She won’t inspire hundreds of news articles nor will she become the subject of any Internet memes. She won’t threaten Ghostface Killah and it seems unlikely that she will ever flirt with a minor on a YouTube livestream.
But the chief commercial officer for Turing Pharma is just as responsible for keeping the price of the life-saving drug Daraprim 5,000 percent higher than it used to be. And as long as the public eye is still trained on the Shkreli sideshow, she’ll get away with it.
….There are more Martin Shkrelis out there, and not all of them are acting like assholes on Twitter. And if the Shkreli Show overshadows the people who still need easy access to a once-affordable treatment, everyone loses. The Pharma Bro started out as a poster child for a pressing problem. He may end up being a red herring.”
Samantha Allen seems eminently qualified to cover the relationship between being an asshole and drug pricing. She has a PhD in Ph.D. in Women’s, Gender, and Sexuality Studies from Emory University. She In 2013, she received the John Money Fellowship for Scholars of Sexology from the Kinsey Institute. She used the money to “research a wide range of media (books, photos, videos, graphic art, tabloids, etc.) on several different sexual fetishes (shoe, foot, nylon, pantyhose, breast, spanking, hair, etc.) dating from across the 20th and 21st centuries.”
Is this a great country or what?
But Dr. Allen is also an asshole expert because she is a misandrist. In case you are wondering, that means she hates men:
“i hate men because it’s not my job to fix masculinity; it’s my job to heal from it and to be together with my sisters as we try to make it through a hostile world. and yet i am expected to patiently educate men on how not to be an asshole. here’s my only tip: stop spending so much time around men. they’re assholes.”
Finally, here’s someone attacking drug companies for changing all human and cultural concepts in the world so widely that treatment is completely considered as a business in the world today..We should revive our traditional medicine which is in harmony with our culture and is naturally cheaper and more useful.”
That last statement is from former Iranian President Mahmoud Ahmadinejad who blamed “Zionist medicine” for polluting our planet with profitable but useless medicines.
You knew it had to come down to the Jews controlling Big Pharma this:
“Martin Shkreli (pictured) is a Jewish businessman (he has relatives living in Albania, and is often referred to as an Albanian). Though his Wikipedia page says he is Albanian and Croatian, he was born and raised in Brooklyn, went to Baruch College, worked for uber-Jewish hedge fund manager Jim Cramer in his teens — and had his own hedge fund by the time he was 21.
When the Jews want to profit more from selling a drug needed to treat sick people, who otherwise would die, they don’t just raise the price by a factor of five or ten. They send someone to raise it by a factor of fifty, wait for the reaction to hit the press, then they pretend to back down… yessir, all the way down to where they had planned to put the price from the beginning.
… This is a Jewish business strategy. Whenever they want to do something that they know will antagonize the public, they have one of their own, or someone under their control, do something even worse, and then they pretend to “correct” their own agent by telling him to stop doing it, and start doing something that isn’t quite so bad instead.”
Or as Dr. Allen put it:
Martin Shkreli became the public face of price gouging because he was so transparent. But Retzlaff’s cool, calm, and collected attempt to spin the same exorbitant price increase for an HIV drug as a net good is arguably more dangerous because it is less obvious.”
There’s no underlying similarity binding these anti-pharma and anti-Semitic rants except varying degrees of paranoia and this observation by George Orwell: “If thought corrupts language, language can also corrupt thought.”
Read More & Comment...
From the very beginning of the hearing, it was clear the expert members of the committee didn’t understand what biosimilars really are, nor the pathway the agency uses to review them.
And yet, at the end of a long day they were asked to vote on this question:
Does the Committee agree that based on the totality of the evidence, CT-P13 should receive licensure as a biosimilar product to US-licensed Remicade for each of the indications for which US-licensed Remicade is currently licensed and CT-P13 is eligible for licensure (RA, AS, PsA, PsO, adult CD, pediatric CD, adult UC)?
Despite open public comment from patients and physicans concerned about extrapolation issues, the vote was 21-3 in the affirmative. It was the vote the FDA wanted. And they got it.
Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified as potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
What does the FDA know that our European and Canadian regulatory cousins do not?
There was also much chatter amongst the panel members about this vote helping to lower prices. Maybe so. Maybe not. Either way it’s not an appropriate discussion for an FDA panel.
Read More & Comment...
The event’s lead-off hitter is Dr. Doug Throckmorton, CDER’s Deputy Director for Regulatory Programs and the FDA’s point-man for opioids. His talk, “The Future of Abuse-Deterrent Formulations,” is a timely must-hear presentation.
Read More & Comment...
Does Califf’s Opioid Announcement Go Far Enough?
Sens. Joe Manchin (D-W.Va) and Edward Markey (D-Mass.) will maintain their holds on the nomination of Robert Califf for the top job at the FDA, despite the agency’s announcement Thursday that it would overhaul its opioid policies.
Specifically, the FDA said it would reexamine its approval, REMS and postmarket policies for opioids in response to a growing abuse epidemic and calls to action from lawmakers.
The senators — along with Sen. Bernie Sanders (I-Vt.) — in January placed holds on Califf’s nomination, with all three citing the FDA’s handling of approving prescription opioids.
A spokeswoman for Manchin tells DID that the senator’s plans have not changed, and he still plans to filibuster and hold Califf’s nomination. Manchin said the FDA’s announcement that it would re-evaluate its risk-benefit framework for the drugs will only “slightly improve” the agency’s response to the opioid epidemic, and that “sweeping changes” are still necessary.
Markey said in a statement that the FDA’s actions are “some important steps” but “fall short of what is needed.”
Andrew Kolodny, director of Physicians for Responsible Opioid Prescribing and the chief medical officer of Phoenix House, tells DID that many of the FDA’s “speaking points” are “meaningless.”
He criticized the agency’s announcement that it would convene an advisory panel before approving any new opioids that lack abuse-deterrent properties, asserting that these meetings should be held for all approvals regarding opioids.
Senator Markey also made that point: “By refusing to convene advisory committees to inform all of its opioid approval decisions, the FDA continues to ignore outside experts who could help stem the tide of tragic deaths and overdoses plaguing the country,” Markey said in a statement. He also said he would continue to hold off on Califf’s nomination “[u]ntil the FDA commits to convene advisory committees of outside experts for all its opioid approval decisions.
Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, tells DID that he thinks the FDA’s approach could make a difference, saying it will make the approval process “more complete.” “I think there will be a higher evidentiary standard on the one hand, but on the other hand there will be a clearly explained pathway as to how to achieve it. They're taking ambiguity out of the process.”
Pitts added that the approach is going to provide guidance on how to develop abuse-deterrent opioids and how to use real-world data to impact post-approval labeling. Read More & Comment...
Celltrion conducted clinical studies of CT-P13 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and is seeking extrapolation of CT-P13 across all seven of Remicade's approved indications including Crohn's disease, pediatric Crohn's disease, ulcerative colitis (UC), pediatric UC, psoriatic arthritis and plaque psoriasis.
In the briefing documents, FDA reviewers said the preclinical, clinical and manufacturing data submitted by Celltrion suggest that it is "highly similar" to Remicade. Agency officials noted that while there were differences in the binding of the Fc regions between Remicade and CT-P13, "it is reasonable to extrapolate conclusions regarding the similar efficacy and safety of CT-P13 and U.S.-licensed Remicade to IBD."
In brief, the FDA recommends approval for all indications mostly based on analytical studies along with some clinical (primarily for RA and AS data). Emphasis on analytics is not surprising based on the FDA biosimilar pathway – but what is interesting (and disturbing) is the absence of available real world data. More on this important patient safety issue shortly.
Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified as potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
AdComm members will be asked to discuss the similarity of CT-P13 to Remicade, whether there are clinically meaningful differences between the two mAbs, and whether there are sufficient data to support extrapolation to the approved indications beyond those studied in clinical trials. The panel will vote on whether CT-P13 should be approved as a biosimilar of Remicade for each of the seven indications.
Interestingly, the FDA has will not ask the panel to discuss any of the comparative real world data available that speaks to relevant clinical outcomes. This is particularly disturbing since (on page 11 of the briefing package) the agency FDA made statements on switching (per RA and AS) that would support the safety of a one-time switch from innovator to biosimilar. This is particularly important since Celltrion is NOT seeking interchangeability.
Should “defacto interchangeability” be an acceptable regulatory pathway?
Specifically absent from the FDA AdComm package is data from a study, from Mercy University Hospital, University College Cork, Centre for Gastroenterology, Mercy University Hospital, Cork, Ireland, which studied the clinical impact of both the innovator product (Remicade) and CT-P13, the Celltrion biosimilar. The findings are important. Specifically, the rates of surgery of the groups were significantly different.
80% of biosimilar patients required hospital readmission versus 5% of the Remicade) group. (p=0.00004). 60% of patients in the biosimilar group needed steroid augmentation of standard steroid tapering protocol with 50% requiring multiple increases in steroid dose versus 8% of those patients on Remicaide (p-value = 0.0007). Over the course of 8 weeks, 93% of patients in the biosimilar group had an increase in CRP with 7% remaining unchanged whereas 100% of patients in the Remicade group had a decrease in CRP (p=<0.001).
The study’s conclusion is not ambiguous, “Our results suggest that biosimilars may not be as efficacious as the reference medicine. The results found reflect the ECCO statement position that the use of most biosimilars in IBD will require testing in this particular patient population and cannot be extrapolated from other disease populations."
The complete poster can be found here.
An American College of Rheumatology abstract of CT-P13 data shows important differences between adverse events in patients with rheumatoid arthritis and those with ankylosing spondylitis depending on whether or not they were switched.
The ACR abstract can be found here.
The efficacy data was good. But the safety data is concerning. But the FDA AdComm won’t be discussing this study either.
Biosimilarity and measurement of efficacy is only one dimension. Attention must be paid to effectiveness relative to real-world patient outcomes data. Regulatory sins of omission are dangerous when it comes to the public health. Read More & Comment...
The FDA has announced a far-reaching action plan to reassess the agency’s approach to opioid medications. The plan will focus on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief.
Importantly, the FDA’s strategies and tactics are not adverse to the well-being of pain patients and avoid measures (such as mandatory advisory committees for abuse deterrent formulations) that would have the negative consequence of chilling investment in the science of abuse deterrence.
The FDA will:
• Re-examine the risk-benefit paradigm for opioids and ensure that the agency considers their wider public health effects;
• Convene an expert advisory committee before approving any new drug application for an opioid that does not have abuse-deterrent properties;
• Assemble and consult with the Pediatric Advisory Committee regarding a framework for pediatric opioid labeling before any new labeling is approved;
• Develop changes to immediate-release opioid labeling, including additional warnings and safety information that incorporate elements similar to the extended-release/long-acting (ER/LA) opioid analgesics labeling that is currently required;
• Update Risk Evaluation and Mitigation Strategy requirements for opioids after considering advisory committee recommendations and review of existing requirements;
• Expand access to, and encourage the development of, abuse-deterrent formulations of opioid products;
• Improve access to naloxone and medication-assisted treatment options for patients with opioid use disorders; and
• Support better pain management options, including alternative treatments.
As one of the cornerstones of this plan, the FDA will seek guidance from outside experts in the fields of pain management and drug abuse. For example, the FDA has already asked the National Academy of Medicine to help develop a framework for opioid review, approval and monitoring that balances individual need for pain control with considerations of the broader public health consequences of opioid misuse and abuse.
“We are determined to help defeat this epidemic through a science-based and continuously evolving approach,” said
Per Rob Califf, the FDA’s Deputy Commissioner for Medical Products and Tobacco “This plan contains real measures this agency can take to make a difference in the lives of so many people who are struggling under the weight of this terrible crisis.”
In addition, the FDA will convene independent advisory committees made up of physicians and other experts when considering for approval any new opioid drugs that do not contain abuse-deterrent properties. The FDA will also convene a meeting of its standing Pediatric Advisory Committee to make recommendations regarding a framework for pediatric opioid labeling and use of opioid pain medications in the pediatric population.
The FDA is also strengthening the requirements for drug companies to generate postmarket data on the long-term impact of using ER/LA opioids. The agency expects this to result in the most comprehensive data ever collected in the field of pain medicine and treatments for opioid use disorder. The data will further the understanding of the known serious risks of opioid misuse, abuse, overdose and death.
The FDA’s full announcement can be found here.Read More & Comment...
On February 9th, the FDA’s Arthritis Advisory Committee will discuss biologics license application (BLA) 125544, for CT-P13, a proposed biosimilar to Janssen Biotech Inc.'s REMICADE (infliximab), submitted by Celltrion, Inc.
If the Adcomm gives a thumbs up and the agency approves the product, this will be the second biosimilar approved in the U.S., but the very first monoclonal antibody, a much more complex molecule than filgrastim.
Apart from the product issues, there are many important policy issues that should be discussed. For example:
Labeling, naming, coding, substitution, non-medical switching and interchangeability are all-important policy issues that FDA has the authority to impact and are appropriate to raise at a high level AdComm.
While extrapolation was allowed for filgrastim, the questions of extrapolation for this product are not as simple or straight forward for the following reasons:
Complexity and Stability
Filgrastim is generally not used as a long-term product for a life-long, chronic disease like infliximab and is much less complex than infliximab, which is nearly eight times larger. Monoclonal antibodies are used in patients with moderate to severe diseases like Crohn’s or ulcerative colitis and disease stability is critical. With biosimilar entry the risk of switching the patient to a new, similar product must be carefully considered due to the complexity of the product and disease state.
Regulatory Authorities Split
Because biosimilars are not identical copies of their reference products, even slight differences in structure can affect the biosimilar’s mechanism of action. Without clinical data in each therapeutic area, it may be challenging to understand the impact of these differences on clinical outcomes. Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified which are thought to be potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
Biosimilar sponsors compare the structure and function of their products to the reference product using a range of laboratory (i.e., analytical tests) tests. Because of the complexity and uncertainty with regard to monoclonal antibodies, we can’t always tell which product attributes (or parts of the structure) will be relevant to ultimate clinical outcome and which won’t be. This is why it’s critical that FDA take a conservative approach and ensure that the biosimilar and reference product are as highly similar as possible, across a wide variety of structural and functional attributes.
Studies Suggest Different Response in Different Disease States
An American College of Rheumatology abstract of infliximab biosimilar data shows difference between adverse events in patients with rheumatoid arthritis (RA) and those with Ankylosing Spondylitis (AS) depending on whether or not they were switched with a 22.5% difference in AS patients that were switched:
* Ankylosing Spondylitis (AS) TEAEs - 48.9% on biosimilar; 71.4% switched from innovator to biosimilar
* Rheumatoid Arthritis (RA) TEAEs – 53.5% on biosimilar; 53.8% switched from innovator to biosimilar.
Regulatory authorities recognize the importance of robust post-marketing safety monitoring for all drugs including biosimilars. What make biosimilars different from other drugs however is that unlike generic small molecule medicines where safety can be assumed to be identical as its branded counterpart, a biosimilar is not identical to its reference drug. Another defining difference with biosimilars is that all biologic medicines may trigger the human immune system to react in undesirable ways such as rendering the medicine ineffective. Small difference between products may result in different effects on the body’s immune system.
* Post-marketing safety monitoring is heavily dependent upon voluntary reporting of adverse events by health care professionals and patients. Unfortunately, this system does not have the capability to effectively monitor and accurately identify adverse events as a result of triggering the body’s immune system. It is unclear how regulators can or will implement robust ways to compare the safety of a biosimilar to its reference product once approved.
It may be February in Maryland – but the heat is on the FDA.Read More & Comment...