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So much for regulatory fraternity …
PhRMA, BIO Open Fire On FDA's Biosimilars Guidance
By Jeff Overley
Law360, New York (August 13, 2014, 7:11 PM ET) -- Pharmaceutical Research and Manufacturers of America and the Biotechnology Industry Association are leading an attack by innovator drugmakers on the U.S. Food and Drug Administration’s most recent biosimilars guidance, saying in letters released Wednesday that it could let copycat products be sold without fully demonstrating safety and effectiveness. In correspondence provided to Law360 following a Tuesday comment deadline, the trade groups each questioned biosimilars policies the FDA proposed in May regarding so-called clinical pharmacology data — relatively early research in small groups of human subjects. PhRMA, for example, took issue with the FDA’s introduction of four categories of similarity — not similar, similar, highly similar, and highly similar with fingerprint-like similarity — saying that the “hierarchy is beyond the scope of the draft guidance.” If the FDA insists on preserving the categories within the guidance, it should eliminate “vague and confusing” definitions that make it unclear how regulators will decide which classification to apply, PhRMA wrote. BIO also voiced concerns with the four categories, specifically questioning the FDA’s statement that a product merely deemed similar — and therefore not comparable enough to qualify as a biosimilar — could be deemed highly similar if additional studies help to erase uncertainties. That additional testing could “expose human subjects to an experimental therapy that had not met the statutory analytical threshold of ‘highly similar,’” BIO wrote. Both organizations have members that are pursuing biosimilars, but they mainly focus on brand-name products, including branded biologics that stand to lose significant market share when biosimilars arrive on the scene. Any delays in finalizing FDA policies on biosimilars therefore may work to their advantage. PhRMA’s letter also suggested that the guidance is murky with respect to when clinical pharmacology data is sufficient to establish biosimilarity. For example, at one point in the guidance, the FDA said that such data “may be sufficient to completely assess clinically meaningful differences between products,” PhRMA noted. But the guidance also said that clinical pharmacology studies, “if done well,” can complement other data and guide future testing. “Based on these passages, it is unclear to PhRMA when FDA believes that clinical pharmacology studies can constitute the full clinical assessment,” the organization wrote. PhRMA and BIO also sounded alarms over the FDA’s approach to safety, specifically the issue of immunogenicity, which can refer to immune system responses that cause allergic reactions or alter a biologic’s effects. The FDA’s guidance said that such data may need to be supplemented by findings from post-approval studies, and both groups expressed concern. BIO, for example, wrote that “full evaluation of safety and immunogenicity should still be necessary before approval” and that the FDA should elaborate on the role of post-approval studies in demonstrating safety. Also, BIO asked the FDA to better explain its suggestion that biosimilarity may be established by looking at a single, scientifically acceptable biomarker — say, blood pressure or cholesterol levels — or at a composite of multiple biomarkers that are "relevant." “While this approach may have utility, it runs the risk of merely increasing the quantity of data without necessarily improving the quality and interpretability of the results,” BIO wrote. Swiss drugmaker Roche AG — parent of U.S.-based Genentech Inc. and a member of BIO but not PhRMA — also submitted a letter seeking more clarity on the four categories of similarity and complaining that the guidance covers more than just clinical pharmacology data. According to a public docket, two dozen letters have been submitted on the guidance, but as of Wednesday, the FDA had published only four of them. Those letters were from Roche, the United States Pharmacopeial Convention, an independent board established by Amgen Inc., and generics maker Apotex Inc., which posed five questions but little in the way of criticism. Sandoz Inc., the first company to request FDA approval along the Affordable Care Act's biosimilar pathway, didn’t immediately respond to a request for a copy of any comments it submitted. Hospira Inc., which is also pursuing biosimilars, directed an inquiry to the Generic Pharmaceutical Association, which did not immediately have comments to share.
As seen in The Hill.
Wanted: Better fact checkers at Consumer Reports
The national public debate over the misuse and abuse of opioid pain medicines has been in the news long enough now for state and federal lawmakers and regulators at the Food and Drug Administration to focus on the real issues rather than the tabloid headlines.
That’s why the latest story on the subject from Consumers Report is so puzzling. Not only is it a day late and a dollar short, but it reaches all the wrong conclusions – providing a distinct disservice to its readers.
The CR cover featuring the story screams, “Deadly Pain Pills!” But the only thing deadly is the reporting which is both hyperbolic and filled with obvious errors and selective omissions.
Specifically, CR has the pain medicine Zohydro ER in its crosshairs. The article calls on the FDA to reconsider its 2013 approval of Zohydro ER and to make acetaminophen standards consistent.
Strangely the piece fails to mention that one of the benefits of Zohydro ER is that it is acetaminophen-free. It also neglects to mention that this very concern was specifically addressed by FDA Commissioner Margaret Hamburg who testified before Congress that, “We recognize that this is a powerful drug, but we also believe that if appropriately used, it serves an important and unique niche with respect to pain medication and it meets the standards for safety and efficacy.”
The investigative tigers at CR call for the FDA to approve only opioids that are “abuse deterrent.” Well, here’s what the FDA commissioner had to say on that subject (also in open public testimony that the CR story either missed or chose to ignore), “It doesn’t do any good to label something as abuse deterrent if it isn’t actually abuse deterrent, and right now, unfortunately, the technology is poor.”
Surprisingly absent from the CR story was any mention of the most promising of the FDA’s initiatives on abuse deterrence; a study (to be conducted by the National Institute for Pharmaceutical Technology and Education) to evaluate opioid product formulations and performance characteristics for solid and oral dosages.
Unfortunately complex systems make for bad media coverage, while simplistic, dramatic demagoguing makes for sexier headlines.
Oops.
CR also believes another reason Zohydro ER should be recalled by the FDA is that it was approved, “against the recommendation of its own panel of expert advisers.” That’s true – but it’s not the whole truth. What the CR authors left out is that, by a vote of 11-2, the experts affirmed that there was no evidence to suggest Zohydro had greater abuse or addiction potential than any other opioid.
“Facts,” as John Adams said, “are pesky things.”
What the newshounds at CR missed completely are the issues surrounding opioid misuse – at present the poor public health stepchild of abuse. In the United States, the use of opioids as first-line treatment for chronic pain conditions doesn’t follow either label indications or guideline recommendations.
In fact, 52 percent of patients diagnosed with osteoarthritis receive an opioid pain medicine from their doctors as first-line treatment as do 43 percent of patients diagnosed with Fibromyalgia and 42 percent of patients with diabetic peripheral neuropathy.
Payers in the healthcare system often impose barriers to the use of branded, on-label non-opioid pain medicines, relegating these treatments to second line options. The result is a gateway to abuse and addiction with opioids.
Another fact conveniently missed in the CR story is that the vast majority of people who use opioids do so legally and safely. A subset, approximately four percent of patients, use these medications illegally. In fact, from 2010 to 2011, the number of Americans misusing and abusing opioid medications declined from 4.6 to 4.2 percent.
How strange that Consumer Reports missed so many facts after all this time.
From today’s edition of the New York Post …
From HIV to cancer to Crone’s, ObamaCare fails the sick
By Peter J. Pitts
Melanie Thompson and HIV patient Brian Albright look over his medical bills and correspondence with his insurance company in Atlanta. Photo: AP
It turns out ObamaCare didn’t solve the problem of “pre-existing conditions” after all. It made premiums more affordable for people with chronic health conditions that are expensive to treat — but at the price of sticking them with unaffordable co-payments for their medications.
The nonprofit AIDS Institute is suing four Florida health insurers for discriminating against HIV/AIDS patients. The complaint says these patients now face prohibitive out-of-pocket drug costs. Sadly, most of the plans sold via ObamaCare all across the country have similar problems — leaving those with chronic diseases without affordable access to the specialty drugs they need.
The Affordable Care Act limits the degree to which insurers can charge higher premiums for sicker patients. But ObamaCare plans found a way around these rules: impose higher out-of-pocket costs for all or most specialty drugs.
Consider the Florida suit. Carl Schmid, the AIDS Institute deputy executive director, says the plans follow a “pattern where every single [HIV/AIDS] drug for some plans was on the highest tier, including generics.” Under these policies, drug costs for AIDS patients can exceed $1,000 a month.
And Florida’s hardly unusual. A new report from consulting group Avalere Health found that a large majority of all ObamaCare exchange plans include similarly high out-of-pocket costs for patients with certain illnesses.
The breakdown of Silver plans (the most popular category) is particularly revealing. In seven classes of drugs for conditions from cancer to bipolar disorder, more than a fifth of these plans require patients to shoulder 40 percent of the medicine’s cost.
And 60 percent of Silver plans place all drugs for illnesses like multiple sclerosis and rheumatoid arthritis in the “formulary tier” with the highest level of cost-sharing.
Nearly every Silver plan across the country, in fact, puts at least one class of drug exclusively in the top cost-sharing tier. In effect, this leaves patients with a given condition — whether HIV or Crohn’s disease — without a single affordable treatment option.
Pre-ObamaCare, about half the states had a system in place for helping people with pre-existing conditions: state high-risk pool plans, which for years offered government-subsidized coverage to patients with pre-existing conditions. But the Affordable Care Act banned those pools.
So now, with exchange plans failing them, the chronically ill have nowhere left to go.
Allies of the insurance industry blame the drug companies for the high price of certain medicines. AARP policy adviser Leigh Purvis, for instance, says cost-sharing levels “wouldn’t be so high if the prices of drugs weren’t so high.” Health-policy advocate John Rother, meanwhile, claims that “reducing price is something [drug] companies could do tomorrow.”
But drug prices aren’t arbitrary. The average biopharmaceutical therapy takes $1.2 billion and anywhere from 10 to 15 years to bring to market. Firms must charge high prices for certain brand-name drugs to make back this substantial investment with enough left over to fund research into the next generation of treatments.
And while insurers like to complain that sophisticated therapies cost too much, they tend to ignore the far higher costs of denying these medicines to patients.
Increased co-pays result in “non-adherence,” failure to take prescribed medications. And that equals increased rates of hospitalization, chronic heart failure and premature death.
And this adds to health outlays: According to a recent study in the Annals of Internal Medicine, non-adherence costs the US health system from $100 billion to $289 billion a year.
In short, by making needed medications unaffordable — and by failing to cover newer, targeted therapies — insurers are jeopardizing patient health. And far from saving money, cutting off access to specialty drugs actually increases long-term health costs.
Specialty medications need to be treated as equivalent to other essential medical services — not as some luxury that only the wealthy can afford. But the ObamaCare law has only made the problem worse than ever.
Peter J. Pitts, a former Food and Drug Administration associate commissioner, is president of the Center for Medicine in the Public Interest.
Here’s something you probably don’t know – once-upon-a-time I was a stand up comic. That’s why I was so intrigued when I got a call from the Daily Show asking for an interview on … opioid abuse.
Opioid abuse?
Well, the interview happened yesterday (the "correspondent" was the charming Michael Che) and it’s still a mystery to me where the humor is in this topic. So why did I choose to participate? (1) It’s a widely watched program that acts as the main source of news for a lot of people. Sad, but true. And (2) The segment will air with or without my comments. I’d rather have the opportunity to offer some truth even in the face of … comedy?
Or in the words of Molière, The duty of comedy is to correct men by amusing them.
The segment will run either just before or just after Labor Day. Stand by for more details.PS/ Whatever the outcome, I will certainly not be as bad as Kathleen Sebelius!
One of the hallmark pieces of FDASIA enshrines the concept of patient-focused drug development. Per the FDA’s own website:
Patients who live with a disease have a direct stake in the outcomes of the drug review process and are in a unique position to contribute to the entire medical product development enterprise. Under FDASIA, the FDA will increase patient participation in medical product regulation.
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Patient Participation in Medical Product Discussions under FDASIA. Sec. 1137 of the new law will assist the agency in developing and implementing strategies to solicit the views of patients during the medical product development process and consider their perspectives during regulatory discussions. This will include:
- Fostering participation of FDA Patient Representatives as Special Government Employees in appropriate agency meetings with medical product sponsors and investigators; and,
- Exploring means to provide for identification of potential FDA Patient Representatives who do not have any, or have minimal, financial interest in the medical products industry. - Patient-Focused Drug Development under PDUFA V. The PDUFA V agreement provides for a new process enhancement under a commitment that will provide a more systematic and expansive approach to obtaining the patient perspective on disease severity or the unmet medical need in a therapeutic area to benefit the drug review process. In other words, the patient perspective will provide context in which regulatory decision-making is made, specifically the analysis of the severity of the condition treatment and the current state of the treatment armamentarium for a given disease.
But patient input needs to be more than anecdotal – it needs to be data-driven so that divisional decisions can be more scientifically-driven by the patient community. And nowhere is that more urgently needed than in discussions over risk/benefit calculations.
The Center for Medicine in the Public Interest (www.cmpi.org) weighs in on this issue with a new paper by senior fellow, Dr. John Bridges (of the Johns Hopkins Bloomberg School of Public Health). His new paper, Identifying the Benefits and Risks of Emerging Treatments for Idiopathic Pulmonary Fibrosis: A Qualitative Study (The Patient, DOI 10.1007/s-40271-014-0081-0) provides important qualitative evidence on stakeholders’ views as to important issues associated with emerging therapies for idiopathic pulmonary fibrosis.
Bridges, et al., identifies multiple issues were identified spanning the impact of emerging therapies, including the need to document the patient experience with treatment, and factors associated with disease progression.
The paper the value of qualitative research both in understanding the benefits and risks of emerging therapies and in promoting patient-centered drug development.
Patient passion is important to share. Bridges and his colleagues go one step further and provide a pathway towards capturing that passion and channeling it into usable data that can be used to impact regulatory decision-making.Ian Read (Chairman and CEO of Pfizer and the current Chairman of PhRMA) recently published a piece on LinkedIn under the title, Why Society Needs a Vibrant Pharmaceutical Industry: Improving Patients' Lives.
Towards the end, Read writes:
I recognize that there are differing views when it comes to society’s perception of the pharmaceutical industry. Many believe we are more focused on making profits rather than finding cures for patients, even though the industry has a long-standing commitment to providing patients access to needed medicines through many different programs globally. There is also a perception that we do not operate in an open and transparent manner when it comes to our clinical data and financial relationships with healthcare providers. This view lingers despite the significant steps that have been taken to increase transparency, even in the face of the current debate that rages over an individual’s right to privacy.
As an industry we are working diligently to improve our standing in society. We understand that we have a great responsibility. We are at the center of society’s desire and expectation for delivering potential cures and new lifesaving treatments. We will continue to fulfill that vital purpose.
Patients are waiting and we are working hard every day to earn their trust.
Fine sentiments and well-crafted words – but working hard alone isn’t enough to earn trust. Pharma must work hard to do the right thing. What does that mean?
Mr. Read offers the following:
Over the course of the past 50 years, this industry has tackled some of the leading causes of disease and life-threatening illnesses.
For example, today the number of people who have died from heart attacks and strokes has declined. In 2008 around 16 percent of the U.S. adult population was taking a statin to reduce cholesterol. This translated into 60,000 fewer heart attacks, 22,000 fewer strokes and 40,000 fewer deaths.
An article published in 2010 by the Journal of Health Economics found that from 1988 to 2000, improvements in cancer survival created an estimated 23 million additional life-years over this period.
And according to the World Health Organization, immunizations save an estimated 2.5 million lives every year. For every $1 the U.S. spends on childhood vaccinations, we save $10.20 in disease treatment costs.
Consider that pharmaceutical innovation has accounted for 73 percent of the total increase in life expectancy between 2000 and 2009 across 30 developing and high-income countries.
Those are, by any measure, extraordinary accomplishments. Why then is the biopharmaceutical industry so roundly pilloried in the press and so low in the general view of public opinion? Working hard, it seems, is not enough.
At PhRMA’s 14th annual meeting in Washington DC. this past April, Read said that industry needs to “fix the misperception gap.”
Pharma must embrace a new paradigm. Rather than focusing on traditional ROI (Return on Investment), they must now also consider Return on Integrity.
Integrity comes in many forms. Honesty. Virtue. Morality. It means not waiting to be told to do it or waiting to see what others do first. Integrity means being principled and, as my father used to say, “A principle doesn’t count until it hurts.”
Mr. Read’s article on LinkedIn is a good start – but there are many other issues that need to be addressed (such as comparative effectiveness, drug pricing, and off-label communications). Trumpeting accomplishments is both important and cathartic – but now its time for the America’s top drug honcho (and his counterparts at other companies) to move on to more contentious and complicated topics.
In fact, new drugs like Sovaldi will not only rescue patients, but also reduce the cost of health care. The reason is simple. Cure are always less expensive than treating the same disease using no or halfway measures. Would Ignagni wail about a cure for Ebola that cost $1000 a pill?
Before HIV medicines came to market, there were nearly 100000 people with HIV were hospitalized. Today, about 38000 HIV patients are hospitalized each year. Hospitalization rates plummeted thanks to HIV drugs. Without HIV medicines, 111000 HIV patients would be hospitalized each year. Fewer people with HIV would be alive.
Sovaldi will produce similar savings. Millman (a health actuarial firm) estimates 984510 with HCV will be treated between 2014 and 2020. Assume everyone treated gets Sovaldi at $80000. That would cost $78 billion or more accurately about $13 billion a year for six years.
Sounds dire right? But Ignagni ignores how new HCV drugs eliminates a 48-week course of treatment for interferon (that is only effective half the time and has flu like side effects) costs about $6.12 billion year. If hospitalization rates drop by half, it will save another $1 billion per year. ($7 billion total.) Over six years insurers will save $252 billion in the process. Insurers will net savings of $174 billion.
None of this takes into account that new HCV drugs increase life expectancy and well being so that people can work, pay taxes and cover the cost of health premiums. Ignagni’s alarms about Sovaldi are intended to divert attention to these facts and to justify sticking more consumers with the cost of a treatment that saves lives and money.
Sandoz’s Filgrastim Biosimilar Relies On Data Extrapolation, “The Pink Sheet” July 24, 2014
Biosimilars’ Next Hurdle In EU Is Physician Opposition To Extrapolation, “The Pink Sheet” August 4, 2014
The Wall Street Journal reports:
Drug Firms Buy $67.5 Million Voucher to Speed FDA Review
Regeneron Pharmaceuticals Inc. REGN +5.80% and Sanofi SA SAN.FR +3.52% are spending $67.5 million on a novel bet they hope will help them outflank Amgen Inc. AMGN +5.43% in the race to get a new class of cholesterol drugs to the market.
The companies are paying the money to acquire a special voucher held by BioMarin Pharmaceuticals Inc. in a bid to hasten regulatory review of their drug alirocumab, one of an emerging group of medicines that lower cholesterol by targeting a gene known as PCSK9.
BioMarin was awarded the voucher early this year as part of an incentive program established by the U.S. Food and Drug Administration to encourage development of drugs for rare pediatric diseases. The voucher entitles the holder to ask the FDA for priority review of a drug application that would otherwise get a standard review. That could shorten the review process to six months from the standard 10 months.
BioMarin received the voucher in conjunction with FDA approval of Vimizim, a treatment for a rare pediatric condition called Morquio A syndrome that afflicts about 800 patients in the U.S. While BioMarin could have used the voucher itself, the program also allows companies to sell a voucher to another company. The voucher doesn't need to be used on a drug for a rare pediatric condition.
The voucher was the first to be issued under the pediatric incentive program, and also the first to change hands.
The complete Wall Street Journal story can be found here.
Scott Gottlieb has a good piece in The Morning Consult about how PCORI has morphed into a bloated grant giving agency with no function or purpose.
Scott commends the leadership of PCORI in trying to make the agency functional and focused and points out that, like much of Obamacare, PCORI's lofty mission to be a key part of his (the president's )purported goal of lowering healthcare costs was never to be realized. PCORI was, like much of Obamacare, a poorly conceived idea developed by social scientists who believe the government can micromanage every aspect of healthcare. And once it can't, well at least the same social scientists can get about $3 billion of money to support some more bland and useless research that will serve as the basis for yet another round of misguided social engineering.
In fact, PCORI was supposed to be like the UK's NICE.. An agency that used CER to bring health care costs to heel by rationing care. To survive politically, the PCORI leadership quickly abandoned that objective and is focusing on grants that study how to include patients in patient centered research. The real CER -- personalized medicine -- is not even funded for a variety of reasons not the least of which is that the PCORI staff deeply believe that central planners armed with patient-centered research on how to study patient-centered outcomes in a patient centered way using patient centered endpoints will do a much better job than point of care molecular diagnostics that capture and share gene expression data..
Gottlieb concludes: "will PCORI fulfill its lofty mission? Truth be told; it was never meant to. The gauzy rhetoric about an agency that would take on the tough questions was just a sales pitch to get PCORI through Congress. The agency’s undersized grants, its bureaucratic structure, and its pious mission were always going to frustrate its ambitions. Feel stressed by all this? Don’t worry. PCORI is studying that."
You could fund a lot of great research on cures for $3 billion. Here's for getting rid of PCORI and using the money for real medical science.
PCORI’s Efforts Could Leave Obamacare Boosters Stressed Out
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.
