Latest Drugwonks' Blog
Yali Friedman, Publisher and Chief Editor of the Journal of Commercial Biotechnology, has an interesting and important essay on how advances in personalized medicine may have the unintended consequence of accelerating the call for US price controls – resulting in fewer new life-saving treatments.
Friedman writes:
Personalized medicine—prescription of drugs most likely to benefit and least likely to harm individual or groups of patients—promises welcome positive changes to healthcare. It may, however, also have negative sequelae originating from incompatibilities with the current healthcare delivery system and the need for regulatory and policy changes to accommodate personalized medicine.
His full article, Will personalized medicine be a driver for widespread price controls, can be found here.
FDA has approved 28 NMEs since Jan. 1, according to agency records, with at least seven PDUFA dates for NMEs between now and year-end. FDA approved 27 NMEs between Jan. 1 and Oct. 31, 2011, and finished the year with 30, the second highest total of NME approvals in the past 10 years. FDA has averaged about 24 NME approvals each year since 2002, with a high of 36 in 2004 and a low of 17 in 2002.
Good article in the Wall Street Journal about the FDA’s efforts to make not-yet-approved medicines available to patients with life threatening conditions.
If you are a subscriber to the WSJ, the article can be found here.
Kudos to the agency – and well deserved.
Last year, nearly 1,200 patients received treatment with experimental drugs through the compassionate-use program for conditions including hepatitis C, cancer and rare diseases like cystic fibrosis. That is up from about 1,000 patients in 2010, the first year the agency compiled data on the program. The FDA says it has been trying to increase participation, including by helping to set up a Web-based seminar that trains doctors how to make use of the program.
The agency allows manufacturers to make their drugs available, but can't require them to do so, and some companies are reluctant to participate before their products have received marketing approval. The FDA says it has been working to win over more companies. It revised its regulations in 2009 to effectively open the program to a greater number of small drug manufacturers. Most companies that provide drugs for the program do so free of charge, but some seek to recoup their expenses, the FDA says. Health insurers generally don't reimburse patients for the cost of the drugs.
"We get calls from family members and there's this sense these are miracle drugs," says Richard Klein, who heads the FDA's Office of Special Health Issues.
In fact, Mr. Klein says, "you can die faster" if there's an adverse reaction to a drug. And even it if does work, it might only add weeks or months to a patient's life, he says.
OSHI doesn’t get a lot of media coverage, nor do they seek it out. But the work they do is crucial to the mission of the FDA – and to the patients they help.
Bravo.
Milton Friedman once said that the FDA was “obsessed with safety.” Some view that as a badge of honor, others not so much.
Two recent FDA advisory committee votes should please both groups.
An FDA panel recently voted 9-6 to recommend approval for Genzyme’s mipomersen for homozygous familial hypercholesterolemia. The positive vote came despite serious hepatic and other risks -- as long as every effort is made to prevent off-label use. A key mitigating factor was disease severity.
Benefit/Risk at its finest.
A second recent adcomm vote (13-2 in favor of approval for Aegerion’s lomitapide for homozygous familial hypercholesterolemia) also points to a more “needs-focused” philosophy and the committee also recommended a REMS targeted off-label use.
Safe Use is the new normal.
This is where it gets interesting. The feds and some consumer watchdogs view this trend as clear evidence of fraud and abuse, that the physicians are “upcoding” the visit levels to increase their income. On the other hand, I’ve spent the last decade trying to educate physicians on how to document the patient encounter so that you can accurately capture the legitimate value of the service provided. So I look at that trend and think to myself “Job well done.”
From the perspective of a practicing physician, the rules that govern the documentation required to capture a service level are deliberately onerous and designed to produce downcodes. They require the doc to collect far more data than is actually necessary based on the actual condition of the patient. You forget to check one box, you leave out one required element, and despite the complexity, gravity and risk of a patient’s condition, you will not be paid for the service. For years, we have been losing money to these archaic rules (they date from 1995), and we have been struggling to stem the leakage of revenue from our practices.
The industry responded to these rules by developing tools to comply with them. The first thing was to have professional coders. Prior to 2000, a substantial majority of ER charts were hand-coded by the physician; now that is quite rare. Then we got templated paper records which prompted the docs to get all the required data points. Now we have EMRs which do the same thing more efficiently. It’s no surprise that as an industry we have gotten better at meeting the guidelines.
And then there is the fact that the ER is a different place than it was in 2000. Our patients are older and sicker. We do more in the ER than was true in the past. Patients are rarely directly admitted any more, but rather get the majority of their admitting workup done in the ER. I don’t know how much of the skew in the above graph is due to these factors, but they shouldn’t be disregarded.
But I don’t like where this is going. The government is desperate, understandably, to save money on healthcare expenditures. They seem to have assumed their conclusion that the increased coding levels is fraudulent and unjustified, and there seem to be few voices disagreeing with them. Furthermore, there is some inappropriate upcoding, and it’s very easy for a patient with an egregious bill or a certain physician (or group) who pushed the envelope too far to be held up as anecdotal proof that doctors are all a bunch of thieves.
Read the full piece here.
At present, 30% of manufacturing capacity is off-line due to FDA inspection issues. That’s a lot of capacity. In fact, according to the agency, 43% of reported potential shortages were due to manufacturing problems.
Safety is non-negotiable and alleviating a shortage by shorting GMPs is a bad and dangerous pathway. Expediency causes as many problems as it solves.
That being said, regulatory discretion must be part of the solution. With 30% of production capacity off-line because of FDA issues, the agency must work with manufacturers to find creative, science-based solutions. If you create a "science- and risk-based action plan," industry can often address quality issues without disrupting supplies of essential drugs.
The FDA might allow some temporary fixes that fall in line with that thinking. According to the FDA’s Jouhayna Saliba (senior regulatory program manager at the FDA's Drug Shortage Program). If a company discovers impurities that could be filtered out, the agency might allow the product to be shipped along with filters and explanations of how they are to be used in order to avoid a shortage, she said.
But who inspects the inspectors? Per that 30% of manufacturing capacity off-line due to FDA issues, perhaps the FDA should undertake an agency audit to see why there’s been such a jump in GMP issues. It’s hard to believe that year-over-year, production quality control has suffered such a significant lapse. Is there something wrong in the way FDA inspectors (many of them still wet behind the ears and eager to please) are doing their jobs?
It’s a question worth asking – and answering.
FDA is stressing the abbreviated part of the biosimilar development pathway, assuring sponsors that they can limit their required clinical demonstration with early analytical work. Rather than clinical evidence, characterization data will play a more significant role since (according to the agency) the purpose of a biosimilar development program is to establish a product’s similarity to the reference product, not safety and efficacy
The nascent pathway has “created cognitive dissonance in industry,” said Janet Woodcock. “People are going to have trouble with this.”
This represents, according to the Pink Sheet, “a tonal shift” for officials, who for most of the pathway’s young life emphasized the complexity of biosimilar products and how clinical studies were expected to be a key part of applications.
Woodcock said sponsors can limit their required clinical programs by bringing extensive characterization data early in the development process.
“The amount of clinical evidence needed, we conceive, is related to the amount of residual uncertainty that remains after you’ve done those less costly, actually more quantitative, and less time-consuming analytical and functional studies.”
According to Kathleen Uhl, deputy director in CDER’s Office of Medical Policy, “The product development for a biosimilar is not a one-size-fits-all. Agency scientists will evaluate the applicant’s integration of [these] various type[s] of data and information to then provide an overall assessment that the biological product is biosimilar to a reference product.”
“What’s most important to illustrate here is the foundational elements of the analytics,” Uhl said. “The more extensive the analytical and functional comparative characterization, then it’s likely to permit a selective and targeted approach to subsequent non-clinical and clinical studies in order to determine biosimilarity.”
Predictability, as with biosimilarity, is in the eyes of the beholder.
Read the entire article but here's the gist of the piece:
"AT Memorial Sloan-Kettering Cancer Center, we recently made a decision that should have been a no-brainer: we are not going to give a phenomenally expensive new cancer drug to our patients.
The reasons are simple: The drug, Zaltrap, has proved to be no better than a similar medicine we already have for advanced colorectal cancer, while its price — at $11,063 on average for a month of treatment — is more than twice as high.Ignoring the cost of care, though, is no longer tenable. Soaring spending has presented the medical community with a new obligation. When choosing treatments for a patient, we have to consider the financial strains they may cause alongside the benefits they might deliver....
This is particularly the case with cancer, where the cost of drugs, and of care over all, has risen precipitously. The typical new cancer drug coming on the market a decade ago cost about $4,500 per month (in 2012 dollars); since 2010 the median price has been around $10,000. Two of the new cancer drugs cost more than $35,000 each per month of treatment.
The burden of this cost is borne, increasingly, by patients themselves — and the effects can be devastating. In 2006, one-quarter of cancer patients reported that they had used up all or most of their savings paying for care; a study last year reported that 2 percent of cancer patients were driven into bankruptcy by their illness and its treatment. One in 10 cancer patients now reports spending more than $18,000 out of pocket on care."
...Avastin costs roughly $5,000 a month: very expensive in its own right, yet less than half of Zaltrap’s price tag. And while the side effects in both drugs are roughly equal, doses of Avastin generally take less time to administer than those of Zaltrap, which makes Avastin more convenient for patients."
When all is said an done, cancer drugs are less than 7 percent of all prescription drug spending. The objections regarding price -- all things being equal -- overlook the cumulative contribution of medical innovation to longer survival, greater health value and lower treatment costs compared to caring for someone who is terminally ill.
But the NYT editorial doesn't say all new drugs are useless or shouldn't be used until and unless proven cost-effective, the default position of the professional class making a bundle off of comparative effectiveness grants.
Rather, it takes into account something the comparative effectiveness crowd never considers: convenience to patients -- a key element to the value proposition in terms of adherence and outcomes.
Avastin actually takes less infusion time – the standard being 90 1st dose, 60 2nd dose, then 30 thereafter. Zaltrap is 60 minutes each time. Avg number of doses in the trial is 7 and change, so infusion time for Avastin is about 2hours less for average patient. That doesn't seem like a big deal but over the course of months, the waiting and preparation not only imposes a cost on patients but could also discourage compliance.
So what if people don't respond to Avastin. Will the Sanofi drug be used. And is it really a matter of selecting one over another. A recent study asked this post-avastin question. Sticking with Avastin (but changing the chemo) prolongs life as much as changing the chemo and going from Avastin to zaltrap. Response rates in the study were small but showed that within a subset of patients being treated for cancers guided by a VEGF-mechanism for longer periods of time increaes survival.
Clinical trials that seek to compare an existing product with a new one are costly and difficult to run because who wants to enroll in them? But the Sanofi drug could be used if it is found to work in a group of patients based upon KRAS mutation or variations in the VEGF signaling pathway.. Information like this can be obtained during clinical trials or in real world settings. The cost and time of producing such findings are dropping as is the process of matching such results to meaningful patient-level outcomes including "hassle" and quality of life.
Perhaps a better title for the op-ed should be In Cancer Care, Value Matters More Than Cost. Does a product prevent a disease from spreading? Does it reduce the time and cost that someone with cancer have to bear? Does it reduce the complexity of treating an illness? And finally, what is the most effective, most convenient and less toxic treatment for individual patients?
Those are the questions MSK sought to ask and answer in a compassionate way.
FDA calling.
The agency has again warned Avon to stop advertising its Anew skin care products using language that makes them sound like drugs.
In September, the regulator had warned L'Oreal SA for making similar claims.
In a letter dated October 5th, FDA warns that the claims on the company's website implies products are intended to affect the structure or function of the human body.
That would make them drugs.
Speaking of DSHEA reform …
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.
