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It's easy to claim Turing Pharmaceuticals 5000 percent price hike of Daraprim is another example of how biopharmaceutical firms do business.
Easy, but untrue.
Here's Adam Feurstein of the Street.com explaining why he nominated Martin Shkreli as one of the worst biotech CEO's of 2014
Someone thought a smart but attention-addled man-child with a Don Bailey obsession and a Twitter account could be a biotech CEO. They were wrong
In a previous post, Adam explains:
In the weeks before his ouster as the CEO of Retrophin (RTRX - Get Report) , Martin Shkreli was buying relatively small amounts of the company's shares on the open market and using his personal Twitter account to convince investors to do the same.
But while talking up Retrophin's prospects publicly and buying some of the stock, Shrekli was selling privately a much larger portion of his drug company holdings. Without public disclosure, Shkreli received almost $3 million in gross proceeds by selling "forward contracts" on his Retrophin stock in early September, according to a filing with the Securities & Exchange Commission made public Monday night.
Shkreli has not been accused of breaking any securities laws during his time at Retrophin. Last August, Retrophin's board admonished Shkreli for a series of inappropriate Twitter posts and the discovery that company employees were using alias Twitter accounts to promote Retrophin stock and make short-sale recommendations on other biotech stocks.
The new disclosure detailing Shkreli's selling of Retrophin shares comes at a delicate time. The former hedge fund manager has tried to restore his credibility and tamp down talk about his behavior and executive decision-making by blaming Retrophin's problems -- and his exit -- on the company's board and reporting by the media. At the same time, Shkreli is trying to raise outside investor money to finance a new company, Turing Pharmaceuticals.
Here's how Shkreli received almost $3 million in proceeds by selling Retrophin shares with delayed public disclosure:
On Sept. 9, Shkreli and an unnamed third party entered into a "prepaid forward contract" under which Shkreli promised to hand over 123,000 shares of Retrophin in two years. In exchange, the third-party buyer paid $1.07 million in cash to Shkreli -- an amount equivalent to 68% of the present value of the pledged Retrophin shares."
Again, courtesy of Feurstein on June 13 2011:
"As Neoprobe prepares to seek U.S. approval for its lymph node mapping agent, a New York hedge fund manager has shorted the stock and is taking an unusual step to prevent the company from getting a review by regulators.Martin Shkreli ofMSMB Capital Managementfiled a citizen petition with the U.S. Food and Drug Administration last week requesting Neoprobe's Lymphoseek be denied a review due to "severe deficiencies and flaws" in the conduct of two phase III clinical trials. Betting against FDA drug approvals is a well-worn (and often profitable) strategy in Wall Street's biotech trading canon. Shkreli, however, is pushing new boundaries by seeking to directly influence the FDA review process in his favor."
In 2013, Shkreli asked to speak before an FDA panel to argue against the approval of Lorcaserin, a weight loss drug made by Arena Pharmaceuticals Inc. He had short positions in both Neoprobe and Arena
And here's an item that occured around the time Shkreli was raising $90 million for Turing.
Retrophin Inc. founder Martin Shkreli, replaced last year as chief executive officer of the biopharmaceutical company, is under investigation by U.S. prosecutors in Brooklyn, New York, for possible securities law violations, according to a person familiar with the matter."
With this as background, it might be a better use of the Fourth Estate's time to ask the following questions:
How did Shkreli raise 100 percent of the $90 million Series A funding for a company with one product which, even at the highly inflated price of $750 a pill would generate less than $40 million in revenue?
At Shkreli sought to drive down the share price of his company's stock in order to get exclusive marketing rights for a product at about a 90 percent discount. While Chief Investment Officer of MSMB He did the same thing in his effort to buy AMAG Pharmaceuticals in 2011 at a bargain basement price. Here's what he said after badmouthing AMAG and driving down the share price:. “Over the past four years, the AMAG board of directors, presided over an 80% decline in the value of AMAG stock. A letter the SEC sent to Shkreli reveals that the Turing CEO is very good a departing from the facts in explaining his investment activities.
How do we know that Shkreli will not do the same with Turing?
A notorious short seller, is it possible that one way Shrekli is using to finance the offering is to use the price hike to short all other biotech stocks?
Should the focus be on limiting the ability of short sellers and patent trolls to create drug companies that are essentially financed and designed to make money by a) bashing the core technologies of other companies as well as your own and b) buying up the marketing rights of one drug and using that, not the actual benefit of the drug, be the reason for huge price hikes?
One other point worth further discussion. In many cases health plans and PBMs have, by putting important medicines in the highest cost sharing tier, have in effect hiked drug prices by 5000%. Isn't that wrong too?
Finally, here's a good history of the way he wound up creating Turing.
The pain community is not happy with the CDC. And who can blame them?
Per the CDC website, that agency is publishing new guideline (sic) “for prescribing opioids for chronic pain. The agency is working for timely release of the guideline while ensuring that the development process:
- Meets scientific standards
- Includes expert consultation
- Allows for appropriate stakeholders to provide input
- Facilitates partnership development to enhance dissemination and uptake
But the agency’s definition of “transparency” has many up in arms. It's a travesty. Here’s what the leading pain organizations had to say to CDC Director Tom Frieden and Debra Houry, Director of the National Center for Injury Prevention and Control:
Dear Drs Frieden and Houry:
As members of U.S. chronic pain management professional associations and patient advocacy organizations, we, the undersigned, are profoundly invested in any and all efforts undertaken that could impact either the positive or negative outcomes of pain treatment. We have been anxiously awaiting CDC’s draft opioid prescribing guidelines, now revealed September 16th.
It was our expectation that the prescribing guidelines would have been
· * Developed in a transparent manner, consistent with best-known evidence
· * Or, where there is no evidence, by incorporating the common elements of long-accepted clinical expert consensus guidelines developed by a dozen organizations dedicated to the safe and effective treatment of patients with chronic pain
· * Consistent with those aspects of opioid medication prescribing and risk mitigation efforts that are actually supported with rigorous clinical trials, i.e. the FDA-approved indications for the full range of opioid formulations.
We were disappointed on all counts and now are deeply concerned that, not only are the CDC draft guidelines inconsistent with established best practices, they will potentially make it difficult for patients who rely on them for pain control to access them from clinicians who are clear on how best to use them.
The CDC slides presented on Wednesday were not transparent relative to process and failed to disclose the names, affiliations, and conflicts of interest of the individuals who participated in the construction of these guidelines. The presenters refused to provide any information other than to read exactly what was written on the slides even when asked directly by audience members to disclose the processes and people who had developed these prescribing guidelines. Since CDC has traditionally not involved itself in developing and disseminating medication prescribing guidelines, and these recommendations are not consistent with current established guides for managing chronic pain with opioids, these process and participant questions are essential to understand.
A statement was made early in the presentation that it is acceptable and common practice to develop clinical recommendations even when there is a limited or non-existent base of evidence for (or against) the recommendation. In those cases, the standard is to convene expert clinicians with vast experiences in the condition and develop consensus around optimal approaches. CDC itself developed and published an analysis of existing guidelines that logically should have been the foundation for these new guidelines.
While there may be slight variances among organizations on specific guideline inclusions or recommendations, there is a broad conformity that extends beyond the focus of the new guidelines. By addressing only how to limit or avoid opioids, the new guidelines will inevitably result in fewer prescriptions overall - including those needed by patients with legitimate medical needs. Chronic pain advocacy organizations hear daily from increasing numbers of constituents who are not being able to access the opioid medications they’ve relied on to live with their chronic painful conditions. That is not an outcome that anyone involved in chronic pain and prescription opioid diversion and abuse wants but this guideline will produce.
In fact, it is CDC’s singular focus on prescription opioid diversion, abuse, addiction, and overdose over any improved understanding of chronic pain incidence, prevalence, trends, and optimal interventions that reveals within CDC an extreme imbalance in its own risk-benefit sensibilities when it comes to this class of medications. In evaluating new medications for approved uses, FDA requires safety and efficacy trials that all approved opioid medications have met. Detailed prescribing instructions are developed based on proven studies. Yet the new guidelines ignore the FDA’s prescribing expertise, recommending different maximum daily doses that appear in no guidelines or package inserts.
We call on CDC to immediately compile, analyze, and report any and all chronic pain data it possesses, managed with or without opioids. Certainly any health condition that impacts one third of our country’s population should, by definition, have a place of priority in CDC’s mission and mandate. CDC has a Center for Chronic Disease Prevention and Health Promotion that reports on arthritis as part of its annual chronic disease monitoring. Diabetes, interstitial cystitis, inflammatory bowel disease are all programs within this center that have, at their core, chronic pain components and may contain useful data. CDC also fields an Annual CDC/NCHS National Health Interview Survey that reports on severe headache or migraine, low back pain, and neck pain among adults. Obviously, a better understanding of how to effectively treat chronic pain should be an essential component to any treatment prescribing guideline. What CDC presented this week is not that.
If the new CDC guidelines reinforced existing recommendations of experts who agree there are tried and true approaches to safely and effectively using opioids to treat chronic pain, it would be a welcomed addition to clinical practices nationwide. Equally important, we need CDC to glean from its prescription opioid addiction and overdose data which cases actually involve chronic pain patients and which involve patients with active substance use disorder so we can help providers better differentiate the two.
The unmet challenge in chronic pain management with opioid treatment is to identify the conditions for which, and patients for whom, opioid use is most appropriate; the regimens that are optimal; the alternatives for those who are unlikely to benefit from opioids; and the best approach to ensuring that every patient’s individual needs are met by a patient-centered health care system. We need CDC to provide some context around the incidence and prevalence of undertreated pain and the related adverse consequences of undertreated chronic pain on all body systems. With these insights it may actually be possible to improve pain care rather than restricting one treatment based on perceived, not quantified, harms to legitimate patients.
We believe the most important outcome of treatment for chronic pain is pain control sufficient to enable people with pain to maintain a high level of patient-determined quality of life and functionality while avoiding or minimizing potential negative outcomes that could outweigh pain control benefits. We believe it is up to the patient, informed by a comprehensive and ongoing discussion with his or her providers, to decide if risks of opioid use apply to them and are acceptable to bear, when compared with the adverse physical, psychological, and quality of life impacts if pain cannot be adequately controlled without opioids. Our concern is ensuring that further stigma and physical harm to patients does not result from policies and guidelines that address only the risk of harm from inappropriately prescribed or used opioids, when what healthcare providers most require are affirmative strategies to help patients manage their pain.
Alliance for Patient Access*
American Academy of Pain Management*
American Cancer Society, Cancer Action Network, Inc.*
American Chronic Pain Association
Center for Lawful Access and Abuse Deterrence
Chronic Pain Research Group at the Clinical Pharmacokinetics Laboratory, University at Buffalo School of Pharmacy and Pharmaceutical Sciences*
Hospice and Palliative Nurses Association
Interstitial Cystitis Association
Massachusetts Pain Initiative
National Fibromyalgia & Chronic Pain Association
The Pain Community
US Pain Foundation
Virginia Cancer Pain Initiative
* Participant in the FDA August 6 meeting
This unfair, unjust, and ill-considered CDC action must not stand.
Some good quotes from A Califf Regime: The Disruptor FDA, Industry Need, by the very savvy
Donna Young of Scrip Intelligence --
The complete story (subscription only, sorry) can be found here.
… If Robert Califf is confirmed as the next commissioner of the FDA – which most in the biopharmaceutical community are anticipating is all but assured – he'll be taking over an agency that's in the midst of some of the most complicated challenges it's ever faced, the resolutions of which have broad implications for drug and device makers.
… The FDA is dealing with an inability to attract and retain the best and the brightest scientists, noted Ellen Sigal, chair of the nonprofit advocacy group Friends of Cancer Research (FOCR). "The salaries are terrible, hiring practices are convoluted and divestiture is complex," she told Scrip.
… Greg Daniel, managing director for evidence development and innovation at the Brookings Institution's Center for Health Policy and a fellow in economic studies at the Washington think tank, said another problem confronting the FDA is its need for consistent resources and funding to maintain and build on the advances the agency has made in developing new tools and refocusing on patients through new expedited development and review programs.
… Peter Pitts, president of the Center for Medicine in the Public Interest, a Washington think tank, and a former FDA associate commissioner during the George W. Bush administration, insisted Califf is the right leader and "precisely the right guy" to handle the knotty challenges ahead for the US regulatory agency – declaring the former Duke University professor's nomination was "the most important health care act the president has undertaken," even more so than getting the Affordable Care Act enacted.
President Obama’s nomination of Califf, announced on Sept. 15, "really is the biggest thing he's done to advance the public health," Pitts told Scrip. "I really believe that."
If confirmed as commissioner, Pitts said he thinks Califf, who he called an "action-oriented guy," will have an "immediate impact for many issues that need immediate attention" at the FDA – most specifically, precision medicine.
The fact that the past few times a new commissioner was being sought by Democratic and Republican presidents and Califf's name kept coming up as a potential contender demonstrates "he's highly qualified" and capable of doing the job, Pitts said, adding that it also shows that "occasionally, there is bipartisan sanity when it comes to health care issues."
What's most important, Pitts said, is that Califf is viewed as a well-respected scientist – both by regulators and industry alike.
Before joining the FDA this past February as deputy commissioner for medical products and tobacco, Califf had worked closely with the agency on several matters, including serving on its Cardiovascular and Renal Drugs Advisory Committee, "so his learning curve is not steep," Pitts said.
He said Califf also is well respected among regulators at agencies outside the U.S. – an asset that could aid the FDA and other regulatory bodies in harmonizing their review processes and rules, which could broadly benefit the drug and device industries.
But one of the greatest qualities Califf possesses, Pitts said, is his ability to innovate.
"He can take a theory and make it a practical reality," Pitts said, adding that he anticipates Califf to lead the FDA to be "partners in innovation" with industry through "entrepreneurial regulation."
"What that means is that Rob Califf can put the FDA at the center of the health care innovation ecosystem," he declared.
… "He's well known to be an innovator," Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio, said about Califf. "He's been innovative in the design of clinical trials and has long been an advocate of finding ways to do clinical trials that are better, cheaper, faster. He's been somebody who has been outspoken about the fact that the approach we use for drug development is too costly and in some cases too long." Nissen said the current FDA is suffering from "years of stagnation."
"The FDA has not moved forward on any important initiatives during this period of stagnation," he argued. "And it needs a new look. It needs somebody to really come in and really shake things up."
Califf, Nissen said, is "capable of doing that … We really actually see the world pretty similarly."
But while Nissen and Pitts showered praise on Califf, Public Citizen's Carome asserted President Obama's candidate to run the FDA was "bad news for patients and public health" because of the former Duke University professor's "long history of extensive financial ties to multiple drug and medical device companies."
But Pitts argued that "in my mind, the commissioner of the FDA should have an extremely up close and personal knowledge of industry to understand what's happening … I think anybody who knows Rob Califf knows he's not swayed by any financial interests," he said.
… Pitts, Nissen and Sigal all advocated for keeping Califf in the commissioner's role long after President Obama leaves office – declaring the FDA chief's job should be a five- or six-year term.
"I've long been an advocate for this not to be a political appointment," Nissen said.
The next critical path is the path to confirmation.
Good story in Congressional Quarterly on President Obama’s nomination of Rob Califf to be the next FDA Commisisoner.
Unfortunately, since CQ is a subscription-only service, I can only provide some snippets:
Califf, according to several former FDA officials, is a believer in new technology and involving the voice of the patient in the drug development process.
"He understands what the future of health care looks like," said Peter Pitts, who led FDA external relations during the George W. Bush administration.
Califf previously was a top official at Duke University's School of Medicine. During a 30-year career at Duke, he was in charge of the Translational Medicine Institute, whose goal is to speed up the development, testing and approval of drugs and devices.
At the time of his appointment, the FDA hailed Califf, a cardiologist, as "one of the top 10 most cited medical authors." Shortly before taking his FDA position, Califf oversaw a vast long-term study that revealed that a cholesterol-lowering drug could help prevent heart attacks in some patients who cannot tolerate a more common cholesterol-reduction method, statins.
But during his years at Duke, Califf developed close ties to players in the pharmaceutical industry. Some believe these relationships will be an asset for someone who needs industry buy-in for his agency's policies. If Califf is confirmed, Pitts said, it "means the FDA can be both the regulator of industry and its colleague in innovation."
The Senate Health, Education, Labor and Pensions Committee would hold a hearing on Califf's nomination.Sen. Lamar Alexander, R-Tenn., the committee chairman, said in a statement that the panel will move promptly on the nomination.
"Dr. Califf has impressive credentials," said Alexander. "The FDA affects nearly every American and needs the certainty of a strong leader. I look forward to hearing from Dr. Califf specifically on how we can move medical discoveries more rapidly through the FDA and other agencies and get safe treatments and drugs into Americans' medicine cabinets."
If Califf is confirmed, he may only have a little more than a year on the job. But FDA observers say that he's already worked hard to earn a rapport with different branches of the agency and policymakers.
Former FDA official Frank Sasinowski, now a consultant, said Califf will be able to "go into congressional hearings and people will understand that he has an appreciation of what it takes to drive innovation and get new therapies out to patients."
If you are a CQ subscriber, the full article can he found here.Read More & Comment...
President Obama has made the most important healthcare decision of his administration. (No, not that.)
The nomination of Rob Califf to be the next Commissioner of the FDA signals the beginning of a new era at the agency that regulates more than a quarter of the US economy. Welcome to the era of entrepreneurial regulation.
Entrepreneurial Regulation means that the FDA can be both regulator of industry and its colleague in innovation. Expedited pathways are Entrepreneurial Regulation. Breakthrough Designation is Entrepreneurial Regulation. The Super Office of Pharmaceutical Quality is Entrepreneurial Regulation. More aggressive use of the Reagan/Udall Foundation is Entrepreneurial Regulation. Patient Focused Drug Development is Entrepreneurial Regulation.
It’s more than time for the FDA to take its place in the center of the healthcare ecosystem.
There are many issues facing the FDA and not just in drugs. Food safety, device reform, dietary supplement regulation. It's a long list. Califf knows the issues and the players -- most importantly those inside the agency. His nomination is both timely and savvy -- particularly with PDUFA reauthorization under way.
Califf’s nomination is an n-of-1 opportunity. When considering who could replace Peggy Hamburg, Rob Califf was the short list.
Put up your Dukes? In more ways than one.Read More & Comment...
I've just returned from Singapore where I spent some quality time with Raymond Chua (the director of the Singapore HSA -- their version of the FDA) and his senior staff. We covered a wide variety of issues ranging from "what's new at the USFDA?" (Answer -- a lot!), global regulatory convergence, and much in between (such as Singapore as a regulatory “third way” in addition to the FDA and EMA).
The HSA directorate was particularly interested to discuss the USFDA's expedited review pathways (breakthrough therapy designation, accelerated approval, priority review, etc.) and some of the ways they’re impacting regulatory policy (i.e., adaptive clinical trial design, senior staff commitment, earlier sponsor/agency interaction). Per Raymond, the HSA is "pathway agnostic" -- an interesting concept that deserves more discussion and consideration in White Oak. He was also keen to learn more about the USFDA's new "Super Office" of Pharmaceutical Quality. (For more on this, see here.)
When it comes to 21st century drug and device regulation, Singapore is a place to study for best practices as well as innovation in both cogitation and action.
The Merlion roars loudly and proudly on behalf of it’s nation’s public health. And there's much the rest of the world can learn from both it's practices and world view.
(And the eats are pretty spectacular too. I recommend the Chili Crab.)Read More & Comment...
He thinks Australia and Switzerland are good examples of how to do price controls right.
In fact, there are several studies of both pricing systems. In Australia life expectancy increased by 11 months for people who had access to new drugs faster. mean age at death increased more for diseases with larger increases in mean drug vintage. Life expectancy for people who had older medicines didn't budge.In Australia’s Pharmaceutical Benefits Advisory Committee recommended only two of twenty-six drugs with a cost per life-year saved greater than $57,000. Only one of twenty-six submissions with a cost per life-year saved less than $32,000 was rejected. Australia ranked 18th out of 20 comparable OECD countries in access to new medicines, with cancer patients waiting over two years after a drug is approved
In Switzerland a study concluded that 17000 life years were gained in 2012 due to the kind of cancer drugs Emanuel claims are NOT cost-effective. In fact the cost per life-year before age 75 gained from cancer drugs was $21228. Moreover, the study found that by delaying access to these medicines as part of the price control program, Swiss cancer patients died sooner than they had to. Finally, another study concluded that Swiss heart patients who used newer cardiovascular drugs in 2003 lived longer than people who used older cardiovascular drugs. (Meanwhile, in the US generic versions of patent medicines are less expensve than the price controlled brand products in Europe.)
Americans with heart disease and cancer live longer than patients in other countries even though many spend more on on these diseases. The price controls Emanuel pushes would save less than .5 percent of total US health spending. They would drive up total costs and make life shorter and more painful for millions.
Read More & Comment...
First there was Orphan Medical (Caronia), then Amarin. Now Pacira Pharmaceuticals has filed a lawsuit against FDA seeking declaratory judgment that the agency may not prohibit them from providing "truthful and non-misleading" information about the use of Exparel bupivacaine.
Pacira is seeking preliminary and permanent injunctions to prevent FDA from taking action against them on the basis of proposed "truthful and non-misleading" speech. The suit was filed in the U.S. District Court for the Southern District of New York.
FDA approved Exparel in 2011 for postoperative pain management. In September 2014, FDA sent Pacira a warning letter asking the company to stop promoting it for use in surgical procedures other than bunionectomies or hemorrhoidectomies. The agency letter also disputed Pacira's claim that Exparel provides pain control "that lasts for up to 72 hours" as an overstatement of efficacy that was "false and misleading."
Pacira argues that, even if the indications it promoted were considered off-label, they still have the right to promote "truthful and non-misleading" information about the drug under the First Amendment and cited the recent district court opinion allowing Amarin to engage in "truthful and non-misleading speech" to promote off-label use of Vascepa.
What do the Caronia, Vascepa, and Pacria cases have in common? Well, for one thing all the plaintiffs are small companies, largely dependent on the sales of a single product for their revenues. Suing the FDA used to be considered a high-stakes gamble, but recent rulings – and the lack of action on the part of the agency to put forward new draft guidance – seem to have changed the risk/benefit analysis. At least for small companies.
(And the odds-makers of Wall Street think so too. Pacira gained $2.71 to $60.18 on Wednesday.)
Can lawsuits by Big Pharma be far behind?
As far as anything from White Oak … Car 54 where are you?Read More & Comment...
When did taking a hedge fund manager at his word become the hallmark of business journalism??
How about if reporters wrote that "the fact that the Ayatollah also planned to use funds to finance terror, he has said, is incidental to the real of achieving world peace."
As for objectivity, Seifert has been a critic of drug prices over the years, claiming that "The free market approach is no longer working to ensure price competitiveness through generic drugs."
That leaves either price controls, which Seifert supports or Kyle Bass wiping out biotech valuations by using a factless assault on the patents of such company.
I can see how price contols would reduce prices. But how exactly does shorting biotech stocks reduce drug prices? Why not challenge patents directly under Hatch-Waxman?
Because the alternative process is, in the right hands, a process that rewards extortion.
The Inter Party Review was designed by Congress to make it easier for a handful of tech companies to swat away frivilous challenges to their patents. Instead, rather than fulfilling its original intent of weeding out weak patents, IPR’s and the Patent Trial and Appeals Board (PTAB) have become “patent death squads” as they strike down 77% of the patent claims under review. The IPR process is being used to undermine confidence in the patent system. A recent article estimates the resulting cost to the U.S. economy as over $1 trillion."
As Peter noted in a recent WSJ op-ed Kyle Bass is leading the way in destroying confidence in patents. As Barron's observed (Seiffert might want to tape this article on the wall above his computer to remind himself of what good reporting is) Bass teamed up with Erich Spangenberg, CEO of IPNav, to challenge what they argue are questionable patents held by pharmaceutical companies to stifle competition from the generic marketplace. (It’s worth noting that Bass’ new partner, Spangenberg, has been described as the world’s most notorious patent troll. IPNav says it has generated over half a billion dollars in licensing revenue in patent-infringement penalties for its clients, which include individual investors, corporations, and universities.)
Bass's greed (and Peter's article) has led to Congress closing this loophole and the board that does the reviews to tighten up it's requirements. A while ago, Seffert predicted that the board's rejection of the Bass attempt to invalidate Acorda Therapeutics patent for it's drug, Ampyra was just a temporary setback.
He wrote: "But according to Lana Gladstein, a partner in the Intellectual Property Department at Nutter McClennen & Fish, the ruling was very narrow, and baed on the fact that the supporting evidence Bass submitted was insufficient. It has no bearing on his attempts to knock out patents held by Biogen (Nasdaq: BIIB) for its top-selling drug, Tecfidera, nor by Shire (Nasdaq: SHPG) for its drug for short bowel syndrome, Gattex." Or I guess his efforts to shake down Celgene or any other companies.
Too bad for Seiffert, Bass has been 0 for whatever in this extortion racket.
Kyle Bass will soon have to find another way to make up for what might huge losses from his investment in oil stocks (pre-price decline) and GM..
Perhaps he can take comfort in the fact that one journalist is in his corner and still regards anything -- no matter how sleazy or destructive -- that knocks down drug prices as a victory.
Read More & Comment...
Previously, the WSJ stated the approval was akin to " firing the starting gun on a new industry" that will reign in drug spending.
More like shooting blanks.
First, it is important to remember, as the FDA noted in it's approval, that " ZARXIO has not been determined to be interchangeable." Which means: No switching.
Second, a biosimilar requires a Phase III trial. Prior to obtaining approval, Novartis-Sandoz had to conduct the PIONEER study (the official title is A Randomized, Double-blind, Parallel-group, Multi-center Phase III Study Comparing the Efficacy and Safety of EP2006 and Neupogen® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy) The trial was initiated in 2011 and the results of the study were submitted in 2014. Several studies estimate it takes 8-10 years and anywhere from $100 million to $250 million to produce one biosimilar. (That does not include the capital costs of failure, delay, etc. ) That timeline is no different than innovative drugs. That fact should squash the conspiracy theorists like Public Citizen or Donald Light and Hagop Kantarjian who claim that's what a new biotech costs to develop since a biosimilar takes NO risk in investing in preclinical and early human studies.
Third, biosimilars will require the same post market surveillance expected of innovator products. My colleague Peter Pitts has articulated the need for this -- and for monitoring marketing claims -- better than anyone.
For these reasons, biosimilars have not been a profitable business. That will change as more biotech products go off patent. But don't expect deep discounts as long as the costs of development increase.
Instead, it is possible that companies producing biosimilars will seek to increase profit margins by developing therapies that add value. Turning an injectible into an oral treatment is one way. Reformulations and drug combinations are others. Companies will likely seek to create niches using diagnostics and finding additional uses for products.
Which raises the possiblity of authorized generic versions. Or not. My guess is that Amgen will compete on price and seek additional indications for Neupogen.
Biosimilars will not save the gazillions estimated by the media. Rather, they will promote the kind of competition one sees in smartphones and tablets: similar functions, different consumer experiences as a result of incremental, but useful, changes in technology.
That's innovation. And that's good for patients.
Read More & Comment...
A group of cancer doctors has apparently decided to rewrite the Hippocratic Oath.
The ancient pledge charges physicians with applying “all measures that are required” for the benefit of the sick. The docs heading up the American Society of Clinical Oncology want to add a caveat — “unless those measures are too expensive. Then just let the patient die.”
The oncologists’ group has developed a “conceptual framework” that relies on cost-benefit analysis to determine the most “valuable” treatments for different patients.
Sounds innocent enough. But healthcare outcomes cannot be reduced to cost-benefit calculations. By focusing on the cost of a treatment — rather than the benefit it could deliver — the oncologists are allowing dollar signs to dictate whether a patient lives or dies.
Under ASCO’s framework, new treatments will be judged “based on clinical benefit, side effects and cost.” Those are the exact same measures health insurance companies use in limiting patient access to treatments. Indeed ASCO wants insurers to use its calculator to “evaluate the relative value of new treatments” as they develop “benefit structures, adjustment of insurance premiums, and implementation of clinical pathways and administrative controls.”
Such “controls” could include shifting drugs to the highest cost-sharing tier of an insurance plan or requiring patients to try older, cheaper drugs before gaining access to the most cutting-edge therapies.
Never mind that the Obama Administration has warned “placing most or all drugs that treat a specific condition on the highest cost tiers discourages enrollment by individuals based on age or based on health conditions” is discriminatory.
The oncologists are effectively asking insurers to discriminate against cancer patients — in direct contradiction of the Affordable Care Act’s intent.
ASCO’s framework openly ignores what really matters — benefit to patients.
Consider how the framework attempts to dictate how long a person “should” live. It claims that patients “overestimate the benefits of treatments that sometimes extend life by only weeks or months.”
In other words, ASCO has concluded that a treatment that can keep patients alive for weeks or months has no real value.
The framework assigns zero value to any treatment that doesn’t increase survival by 20 percent. Right off the bat, numerous treatments for pancreatic, brain, lung, and stomach cancer today would be deemed worthless by the formula.
That 20 percent figure is completely arbitrary. Consider the case of someone with lung cancer who is alive today because of the accumulation of treatments that never made that arbitrary threshold. Cardiologists hailed a just approved drug that reduces the risk of death from heart failure by 20 percent as revolutionary.
Under ASCO’s framework, sorry — not good enough.
Between 1987 and 2000, various AIDS therapies increased patient life expectancy by less than 20 percent a year. Had ASCO’s framework been in force then, thousands of AIDS patients who benefited from those treatments would not be alive today.
ASCO defends its guidelines by claiming that expensive new treatments have sown “unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.” The American healthcare system can’t afford limitless spending on cancer treatments, the group says.
It’s true that spending on cancer drugs has risen. In 2014, it topped $100 billion. But that figure represents just 1 percent of U.S. healthcare spending.
What’s more, these medicines work — and are worth their price tags.
Successful drug therapies reduce overall medical costs by diminishing the need for future doctor visits and hospital stays. According to a study from the Center for Value and Risk in Health, specialty drugs often cost more than traditional drugs but “also tend to confer greater benefits and hence may still offer reasonable value for money.”
Successful treatment does more than just lower health costs and offer patients priceless extra time with loved ones. It also benefits the nation. According to one study, cancer survivors have contributed $4.7 trillion to the economy since 1990, simply by living and working longer.
Indeed, according to a Health Affairs study, “current technology assessments, which often determine access” to cancer therapies “may be missing an important source of value to patients and should either incorporate hope into the value of therapies.”
By valuing treatments based on what they cost insurance companies rather than the benefit they provide to patients and their families, the ASCO framework violates both the letter and spirit of the Hippocratic Oath. It should be scrapped before it puts patients in danger.
Read More & Comment...
Ray and C-Path has done more to advance personalized medicine than most. C-Path – working closely with pharma and the FDA -- have led the development of tools and markers that are now routinely used in clinical trials to more quickly and accurately developed tools matchpatients to treatments that deliver the most benefit relative to risks.
When C-Path was first launched it was difficult to bring together patients, researchers, private companies and regulators. Under Ray’s stewardship and with the quiet but essential support of the FDA (especially Janet Woodcock) the collective intelligence C-Path brought together has been instrumental in transforming the clinical trial landscape around the world
And the best is yet to come: As current C-Path CEO Marsha Brumfield has written: “the boundaries are expanding with the growing realization of the substantial benefit that can result from new discoveries (such as biomarkers, modelling tools and clinical outcome assessments (COAs)). Even clinical data, traditionally considered proprietary, are contributed to pooled databases to help solve prespecified research questions.
The tools and methods created through sharing information precompetitively are changing the landscape of clinical trial design, enabling trials to be more optimally designed and executed. “
Peter and I are proud to have had Ray as a ‘rabbi’ and an ally in promoting personalized medicine. We look forward to working with him and C-Path in the years ahead. Read More & Comment...
HHS's Health Resources and Services Administration (HRSA) has issued draft guidance on the 340B program that addresses some of industry's concerns with the program. Per BioCentury, the guidance includes a clearer definition of 340B-eligible patients.
The 340B program is intended to provide discounted outpatient drugs to hospitals that serve a disproportionate share of poor and uninsured patients. The 340B hospitals can then dispense the discounted drugs to their non-Medicaid outpatients and use the savings to pay for the care of indigent patients. However, the number of 340B-eligible entities and discounted drugs sold to those entities has grown over the last several years, and industry has said some hospitals are not using the money to pay for charity care and are dispensing the discounted drugs to individuals who are not patients of the hospital.
In the draft, HRSA clarifies which patients would be eligible for 340B: those who receive care at the hospital and who have received a prescription from a provider directly affiliated with the hospital. The rule notes that a patient would be ineligible if the drug is dispensed while they are still an inpatient; if the only service provided by the hospital or provider is to dispense or infuse the drug to the patient; if the patient's physician has credentials or privileges at the hospital but who is not an employee of the hospital; or if the patient is an employee of the hospital but may get care elsewhere.
Additionally, if patients of the covered entity choose to have their prescription filled at a pharmacy not affiliated with the hospital, the drug would be ineligible for the discount. The guidance also would allow manufacturers to audit covered entities if the manufacturer "has reasonable cause" to believe that the entity is providing duplicate discounts to Medicaid patients or diverting drugs to ineligible patients.
The draft guidance will be published in the Federal Register on Friday. Comments are due October 27th.Read More & Comment...
On Tuesday OMB completed its review of a proposed rule entitled "Designation of Official Names and Proper Names for Certain Biological Products."
It's as predicted ... and good news.
According to the Wizards of White Oak, “ Our current thinking is that shared nonproprietary names are not appropriate for all biological products. There is a need to clearly identify biological products to improve pharmacovigilance, and, for the purposes of safe use, to clearly differentiate among biological products that have not been determined to be interchangeable. Accordingly, for biological products, we intend to designate a nonproprietary name that includes a suffix composed of four lowercase letters. Each suffix will be incorporated in the nonproprietary name of the product.
This naming convention is applicable to biological products previously licensed and newly licensed under the PHS Act. The nonproprietary name designated for originator biological products, related biological products, and biosimilars will include a unique suffix. However, FDA is considering whether the nonproprietary name for an interchangeable product 2 should include a unique suffix, or should share the same suffix as its reference product. FDA invites comment on the draft guidance and solicits comments on ways to improve active pharmacovigilance systems for the purposes of monitoring the safety of biological products.
"The official names and proper names of these products would include distinguishing suffixes composed of four lowercase letters and would be designated as filgrastim-bflm (BLA 125553), filgrastim-jcwp (BLA 103353), filgrastim-vkzt (BLA 125294), pegfilgrastim-ljfd (BLA 125031), epoetin alfa-cgkn (BLA 103234), and infliximab-hjmt (BLA 103772). Although FDA is continuing to consider the appropriate naming convention for biological products, including how such a convention would be applied retrospectively to currently licensed products, FDA is proposing to take action with respect to these six products because of the need to encourage routine usage of designated suffixes in ordering, prescribing, dispensing, recordkeeping, and pharmacovigilance practices for the biological products subject to this rulemaking, and to avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway."
A win for sanity and patient safety.
Also, if you'd like more on the related biosimilar J-Code issue, see here.
Over at Forbes, the always thoughtful Matt Herper asks, “Remember when the FDA rejected drugs?”Per Matt, “As recently as 2008, companies filing applications to sell never-before-marketed drugs, which are referred to by the FDA as “new molecular entities,” faced rejection 66% of the time. Yet so far this year the FDA has rejected only three uses for new chemical entities, and approved 25, an approval rate of 89%.”
(These numbers come from a new analysis commissioned by Forbes from BioMedTracker. The way BioMedTracker follows new molecular entities is slightly different from the way the FDA does. BioMedTracker users want to know about every use of a new medicine. That means that the 2015 rejection count includes rejections of Avycaz, a new antibiotic from Allergan, for hospital-acquired pneumonia, and selling Jardiance, a diabetes drug from Eli Lilly and Boehringer Ingelheim , in combination of metformin. But Avycaz was approved for two other uses and Jardiance is on the market by itself.)
Herper, “… it’s worth sticking to BioMedTracker’s definitions, because it allows us to compare this incredibly high approval rate with the past. And that tells a story of an agency that has been giving the green light more and more often.”
Interesting stuff – but what’s missing is a discussion of how the evolution of regulatory science has impacted the dynamic relationship between the FDA and the innovative pharmaceutical industry and has changed over the course of time (by design, and largely through the mechanism of PDUFA negotiations) the quality of NDAs reaching agency review.
More agency/sponsor meetings earlier in the process not only result in better submissions (more likely to be approved because of higher quality science and more sophisticated protocols), but fewer applications of questionable value . As one senior FDA official told me yesterday, “We’re seeing fewer dogs.”
Another factor that’s important to consider is that failed NDAs are expensive. The following figures are illuminating.
- A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.
- Shifting 5% of clinical failures from Phase III to Phase I reduces out-of-pocket costs by $15 to $20 million.
- Shifting failures from Phase II to Phase I would reduce out-of-pocket costs by $12 to $21 million.
The good news is that more R&D time, talent, and treasure is being focused on personalized medicine using more sophisticated tools (i.e, biomarkers). Failure is being found sooner, targeted clinical success is easier to predict earlier – and can be expedited through the regulatory process through many new and exciting review pathways (i.e., Breakthrough Designation).
(PS/ Those who don’t think the FDA has “adaptive licensing” opportunities don’t understand what’s going on. And those who choose to blame the FDA for biotech investor anxiety had better find some new excuses.)
Those who wave their arms about the FDA “approving everything” don’t see (or choose not to see) the important success story behind the headline. That dog don’t hunt.Read More & Comment...
Let's set aside the survey's skewed approach to polling: It singled out prescription drugs for such polling (i.e. there was no question asking people if they knew what they paid for drugs was already controlled -- by health plans -- and that prices were increasing though drugs remained a small share of insurer costs) and it undersampled Republicans and healthy, middle income people. Indeed, the oversampling of Democrats and Independents and the focus on drug prices appears to be part of a broader effort to get drug price control referendum on the ballot in key primary and battleground states like Ohio and California.
Let's instead ask what is the implication of the findings.
According to KFF CEO Drew Altman..
“Rightly or wrongly, drug companies are now the number one villain in the public’s eye when it comes to rising health-care costs,” said Foundation President Drew E. Altman, Ph.D. “People want to rein in the cost of prescription drugs, and just about anything we poll on with that aim gets public support.”
Altman did say that. But not about the recent poll. He said it about a survey taken a decade ago.
The same could be said about other surveys conducted by Kaiser or by their partner in polling, Harvard's Robert Blendon..
In 1984 seventy seven percent of Americans favored prices controls on all medical services. In 1994 that figure was 72 percent.
I bet if I surveyed people to see if they favored price controls on data plans or college tuition or food, I'd get the same number.
All of which proves what polling pioneer Daniel Yankelovich concluded after looking through mounds of Gallup polling data:
The factual ignorance and fickleness reflected in surveys like the KFF tracking polls are often counterbalanced by a remarkable sureness of judgement in applying basic values...
These polls generate headlines and help groups supporting such referendum to raise money. They don't shape policy. In fact, with one or two exceptions that were disastrous (Truman and Nixon's wage and price controls) the American electorate has shied away from outright price controls or laws that would limit the choice of medicines to what is cheapest such as mandatory generic substitution.
As a result, American has since the 1960s, outpaced the world in the development of important treatments for HIV, cancer, Hepatitis C and heart disease that -- since 1990 -- have reduced death and disability as well as made treating people with these illnesses much less expensive (and more effective) compared to older therapies.
So perhaps in addition to polls and ballot initiatives promoting price controls, stakeholders and patient groups should commission surveys and propose referendum about how health plans limit access to new medicines by hiking drug prices and saying no to new medicines.
Read More & Comment...
In the immortal words of Don Draper, “If you don't like what is being said, then change the conversation. And nowhere is that more true than in our national dialogue over opioid pain medications.
Senior leadership at the FDA has returned again and again to the role the agency must play in facilitating physician and patient education -- and not only through labeling language. Former FDA Commissioner Hamburg specifically mentioned CME and working to develop (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.
“It all comes back to provider education,” she said. Amen.
Education – the Hamburg Manifesto.
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 used by the right patient in the proper manner.
In keeping with that philosophy, an important announcement from Purdue Pharma:
Purdue Pharma L.P. Launches TeamAgainstOpioidAbuse.com
New Resource Aimed at Educating About Opioid Analgesics with Abuse-Deterrent Properties and Team Efforts to Deter Abuse of Prescription Medicines
STAMFORD, Conn., August 17, 2015 – Purdue Pharma L.P. proudly introduces Team Against Opioid Abuse, a new website designed to help healthcare professionals and laypeople alike learn about different abuse-deterrent technologies and how they can help in the reduction of misuse and abuse of opioids. Combating misuse and intentional abuse of prescription pain relievers involves more than just the person holding the prescription pad. It is a team effort, including pharmacists, nurses, counselors, caregivers, patients, and payers, both public- and private-sector. Public health experts have stated that Opioids with Abuse-Deterrent Properties (OADP) are an essential component of a comprehensive, evidence-based strategy to reduce opioid abuse that requires coordinated and sustained efforts from the healthcare team along with multiple other players, such as manufacturers, policymakers, regulators, educators, and law enforcement.
“Education about the proper use of opioid analgesics is a top priority at Purdue Pharma. Everyone on the team should understand their role and responsibilities, so they can do their part in combating abuse of opioids, while ensuring their availability for appropriate purposes,” said J. David Haddox, DDS, MD, Vice President, Health Policy, Purdue Pharma L.P. “Opioids with Abuse-Deterrent Properties are one tool to help the team in their efforts in fighting drug abuse. We developed this website to inform everyone who influences how drugs are prescribed, taken, stored, and destroyed, when no longer needed.”
Opioid abuse is a critical problem in America and one that healthcare professionals, payers, law enforcement, policymakers and drug makers are all working to combat. The 2013 National Survey on Drug Use and Health reported that, among persons age 12 or older in 2012 to 2013, approximately 68 percent of people who used prescription pain relievers for nonmedical purposes said they got the medicines from a friend or relative, for free, by purchase, or by theft. In 2011, the White House identified prescription drug abuse and misuse as a major public health and public safety crisis.
Using clear graphics and easy to understand language, the website features sections about why it’s critical to deter abuse and how all the members on the healthcare team can make a difference. It also outlines the 2015 Food & Drug Administration’s Guidance on Abuse-Deterrent Opioids — Evaluation and Labeling, which informs drug developers about FDA’s current thinking on what kinds of testing potentially abuse-deterrent opioids should undergo. Because FDA states that having information about an opioid’s abuse deterrence available for healthcare professionals and patients, the website also reviews how Section 9.2 of a drug product’s Full Prescribing Information is the key to identifying opioid formulations with FDA-approved abuse-deterrent properties.
The Team Against Opioid Abuse website can be can be accessed at http://www.teamagainstopioidabuse.com.
 Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. http://www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.pdf. Accessed August 8, 2015.
2 White House Office of National Drug Control Policy. Epidemic: Responding to America’s Prescription Drug Abuse Crisis. 2011. https://www.whitehouse.gov/sites/default/files/ondcp/issues-content/prescription-drugs/rx_abuse_plan.pdf. Accessed August 8, 2015.
3 Food and Drug Administration, Center for Drug Evaluation and Research (CDER), US Department of Health and Human Services. Abuse-Deterrent Opioids — Evaluation and Labeling: Guidance for Industry. Accessed August 8, 2015. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm334743.pdf.
Well done Team Purdue.Read More & Comment...
Dear President Carter:
I was sorry to learn that you are fighting an advanced form of cancer that has spread to your liver and other parts of the body. There is good news, sort of.
As a recent article in the Boston Herald noted:
Former President Jimmy Carter revealed yesterday that he will undergo treatment for cancer that has spread to various parts of his body — and doctors say that despite his advanced age, the 90-year-old may fare well thanks to recent advances in personalized medicine.
“With cancer cells, there are many different mechanisms that make them grow, and a lot of the science has been dissecting genes and proteins that cause it,” said Dr. Andrew M. Evens, director of Tufts Cancer Center. “There’s work around identifying treatment for the patient’s individual cancer and doing it at a genetic level.”
Not so fast Mr. President.
Even as a former President, you will be faced with what is called “step therapy” or “quality pathways” that determine what treatments you get. You have to fail first on the first step of therapy before getting to up to five other ‘approved’ treatments before getting to the ‘advances in personalized medicine.’
You were a plain spoken president, so I probably don’t have to tell you that for people with advanced form of cancer, ‘fail first’ is code for getting sicker and closer to death.
Health insurers claim these pathways don’t affect outcomes. But they refuse to cover the advances that have a very good chance of keeping you alive and well.
Neither the tests for the genetic makeup of your cancer cells to identify where it started, and guide treatment are not at the end of any of these pathways. Under the Affordable Care Act, anything not on a pathway has to be paid for in full by you.
You might think that your doctor will fight to get you the treatments that could save your life.
Sorry to disappoint you.
The leading cancer doctor group -- The American Society For Clinical Oncology (ASCO) – has developed a calculator of value that treats all patients as the same; ignoring the genetic variation in patient response that allows doctors to personalize care.
Indeed, ASCO wants insurers to use their calculator to “evaluate the relative value of new treatments” as they develop “benefit structures, adjustment of insurance premiums, and implementation of clinical pathways and administrative controls.”
That’s not good news either. I’ll give you a couple of examples. I read that you have a family history of pancreatic cancer. So I used the ASCO calculator to come up with a value score (the highest score is 130). The most common treatment for advanced pancreatic cancer that has spread everywhere adds, on average, about 2.5 months of life. That’s worth a whole 32 points. But then 20 points are deducted because of side effects, leaving you with 12 points of “net health benefit” out of 130 which the app helpfully notes will cost $5000 a month. Other treatments that provide less survival and are cheaper are given a higher score. Guess which treatments you have to use before getting to the most effective treatment covered?
The news is even worse if you have advanced colorectal cancer. The newest drugs add more survival for this deadly disease. But ASCO doesn’t think it’s worth more than 16 points. Deduct 20 points because ASCO doesn’t like the side effects (rashes, nausea, fatigue) and you’re in negative territory. According to ASCO, that treatment has no clinical value at all. And the advances Dr. Evens mentioned aren’t even measured. And they won’t until randomized trials that take years to organize and complete are published.
It’s sad and ironic. You lead a 30-year effort to eradicate guinea worm disease around the world. The disease is not fatal but extremely painful and debilitating. In 1986, there were an estimated 3.5 million cases in 21 countries in Africa and Asia. Your effort was criticized as not cost-effective from the start. You ignored the bean counting because it only focused on 2-3 measures of value. (Sound familiar?)
Today, that number has been reduced by more than 99.99 percent, with the vast majority of cases remaining in South Sudan.
It’s a good thing it was you – not the alliance of insurers and ASCO – tackling that challenge. Unfortunately they are putting a price tag on whether you live or die. Maybe you can change that. A grateful nation is pulling for you to win one more campaign.
Read More & Comment...
The debate over off-label communications doesn’t begin or end with the Caronia or Amarin decisions. It’s a continuing dialogue between manufacturers and the FDA, between doctors and patients, between doctors and academics, between lawyers and judges, and between advocates on all sides.
And the red thread that ties these conversations together is responsible off-label communications. Not sales strategies. Not DTC tactics. Not managed market negotiations – the responsible sharing of truthful and accurate information.
It’s important to say early in the conversation that almost no one is against sharing valuable information about FDA-approved medicines. The discussion – the heated discussion – is over how (or if) that conversation should be regulated by the FDA.
Steve Jobs said, “Innovation distinguishes between a leader and a follower. And make no mistake, off-label communications is about innovation. Innovation in the safe and effective use of medicines. Off-label communications is about getting the right medicine to the right patient in the right dose at the right time – even though the right medicine or the right dose may not correspond precisely to the FDA label.
But who is the leader and who is the follower? Or perhaps a better question to ask is, why can’t we all be leaders?
Off-label communications, properly done, advances precision medicine, delivering speedier positive patient outcomes, and reducing costs to our healthcare system. Off-label communications provides patients with more options for effective medicines.
Those who think that the argument over off-label is just about marketing and sales are looking at this issue through very narrow blinders.
What is the role of the FDA is off-label communications. Well, first let’s stipulate that the FDA doesn’t regulate the practice of medicine. Then let’s discuss the fact that the agency can (and indeed must) help to facilitate the free and fair dissemination of timely, truthful, and trustworthy scientific knowledge.
Also, initial licensing approval is not based on data for every possible indication. Initial approval is based on a “best foot forward” approach. But that doesn’t mean there isn’t robust scientific evidence to support broader therapeutic uses. In fact, initial approvals, based on a narrow, randomized population, only provide a window into future clinical possibilities.
According to the House Energy & Commerce Committee’s 21st Century Cures Initiative initial white paper:
Communication about how certain treatments are working in certain patients is happening through a multitude of media around the globe. These conversations between and among doctors, patients, researchers, and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients.
Off-label communications is about recognizing that the speed of scientific discourse impacts clinical practice years before it drives official label changes.
You don’t have to look much further than oncology and many orphan diseases to see that off-label use is regularly considered first line therapy. And payers in the US and elsewhere reimburse off-label prescribing. Why? Because it enhances outcomes.
How do physicians learn about off-label usage? Medical meeting presentations, professional journal articles, discussions with their peers, and through materials from manufacturers. Please note that I haven’t listed DTC. There is a difference between off-label communications and off-label marketing – and it is a distinction with a difference.
So, what do academics and physicians, payers and patients know about off-label communications that the FDA does not? Asked in a more progressive way, how can the FDA be an accelerator rather than a sea anchor when it comes to facilitating off-label communications?
In a word, the answer is clarity. Alas, regulators love ambiguity because it gives them unlimited options. And nowhere is this more evident than when it comes to issues concerning communication. It would be generous to call the FDA’s views on the dissemination of off-label information ad hoc. With the important exception of the agency’s guidance on Good Reprint Practices. According to the March 2014 revised guidance, reprints that discuss off-label use mustn’t:
- Be false or otherwise misleading;
- Recommend or suggest use of the product in such a way that the product is dangerous to health when used in the manner suggested; nor
- Be marked, highlighted, summarized, or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use.
Those are pretty broad guideposts. More interesting and germane to current events are those related to Clinical Practice Guidelines (CPG):
Any CPG that includes information on unapproved or uncleared uses must meet Institute of Medicine (IOM) standards for whether it is a “trustworthy” guideline. According to IOM, a guideline is “trustworthy” if it:
- Is based on a systematic review of the existing evidence;
- Is developed by experts in the subject area;
- Considers important patient subgroups and patient preferences;
- Is transparently developed and funded such that biases are minimized;
- Provides logical relationships between treatment recommendations, health outcomes, and includes the quality and strength of the underlying evidence; and
- Is reconsidered and revised as new information becomes available.
Beyond this, what will the FDA do next? More importantly, will it lead or follow, or follow and then lead? And this brings us to the recent court decisions in the Caronia and Amarin cases.
The Caronia decision, a 2012 decision from the Second Circuit Court of Appeals, overturned the conviction of Alfred Caronia, a sales representative for Orphan Medical, which was later acquired by Jazz Pharmaceuticals. After Caronia was caught talking to physicians about various off-label uses of the narcolepsy drug Xyrem, the court said the First Amendment protected truthful and non-misleading off-label speech. Key words, “truthful and non-misleading.”
That’s a good off-label equation: Truthful + Non-Misleading = Trustworthy.
Although the agency said that the decision wouldn’t impact it’s views and practices concerning the regulatory oversight of off-label communications, the decision, combined with increased pressure from industry, forced the FDA to put the issue of off-label communications on the front burner.
Unfortunately, it was put on the front burner on a low flame.
Between Caronia and Amarin, the FDA issued some very valuable draft language on the issue. Under the proposal, FDA would not “object to the distribution of new risk information that rebuts, mitigates, or refines risk information in the approved labeling.” The studies must be “well-designed” and “at least as informative as the data sources” that the FDA used in generating the official warning.”
The new FDA draft guidance opens the door for companies to share truthful, scientifically accurate, and data-driven information with healthcare professionals to inform treatment decisions. For example:
Observational data and “real world evidence”
¡ Information on the safety and effectiveness of medicines taken from medical records based on actual use of approved medicines.
¡ Information on the safety and effectiveness of medicines in sub-populations including gender and race. Such information can help healthcare professionals tailor their treatment to meet the needs of individual patients.
Observational and comparative data
¡ Information from the use of a medicine outside of randomized clinical trials, especially comparisons between two or more therapies.
¡ Healthcare economic data and information on the economic value of medicines can improve the efficiency of patient care.
Information on medically accepted alternative uses of medicines
¡ Information on new uses of approved medicines that are listed in major compendia and/or routinely reimbursed by the federal government and major payers.
Things seemed to be moving ahead and the FDA seemed to be driving the conversation – and then came Amarin and it’s drug Vascepta – approved by the FDA for treatment of patients with “Very High” triglycerides.
In April, the FDA rejected Amarin’s claim for “Persistently High” triglycerides and also decided Amarin couldn't include clinical trial data in Vascepa labeling about the extent to which the pill may effectively treat people with slightly lower levels of triglycerides.
In May Amarin filed a lawsuit in Federal Court claiming it “finds itself in a bind,” since it “may not freely communicate truthful and non-misleading information about Vascepa to health-care professionals…without fear of criminal prosecution and civil liability.” In its lawsuit, Amarin included a list of medical journal articles it would like to distribute to physicians.
In June, the FDA sent a letter to Amarin saying the types of materials the drug maker would like to distribute to doctors actually would not be a problem and “would not consider the dissemination of most of that information to be false or misleading.” Then the FDA suggested that Amarin might have known this if the drug maker had discussed the issue before filing its lawsuit, “as other pharmaceutical companies sometimes do.”
Earlier this month the court agreed Amarin materials are truthful and took the government to task for essentially arguing that speech alone can be the basis for liability and that the agency’s action is at odds with the Caronia holding and the First Amendment.
Post-Caronia and pre-Amarin, hoping to maintain its ability to apply “regulatory discretion, “the FDA signaled it was going to loosen the reins on off-label communications. And, in fact, this was part of the government’s argument in the Vascepta case. The Judge asked when the FDA would be issuing further guidance on off-label communication, asking if it would be in 2015 or afterwards, or before Labor Day. The government’s attorney said she had “no idea” when the agency would act or if more speech will be permitted when it does. Bad answer.
So what happens now?
I predict that the FDA will continue to develop its new thinking on off-label (informed and influenced by both the Caronia and Amarin decisions). It will then issue a more complete draft guidance and collect feedback via a Federal Register docket. That’s the way the system works and rules must be follows.
I further predict, barring overly ambiguous and wimpy language from the agency, that most pharmaceutical companies will declare victory and follow the FDA’s lead. That being said, the agency will need to carefully monitor i’s off-label oversight – and his means a lot more than the usual and customary OPDP review. It means senior management attention to how the agency views “trustworthy” and a very careful eye on any actions it considers taking.
All this to say that off-label communications is now on the agency’s front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”
Can the FDA recapture a leadership role in the off-label conversation? I believe it can – and will. But it will require the agency to trade ambiguity for predictability because, when it comes to trustworthy off-label communications, predictability is power in pursuit of the public health.
Stay tuned.Read More & Comment...
Dr. Jack Kevorkian
Lowell Schnipper, the chairman of the ASCO Value Framework Task Force was also part of a group that supported Dr. Jack Kevorkian and pushed to legalize physician-assisted suicide.
It raises the question: Does the Value Framework recycle the arguments and assertions Dr. Schnipper made in pushing euthanasia as an option for cancer patients in determining how to value drugs and why?
To my mind, it does.
Schnipper, who is also Chief of Hematology/Oncology at Beth Israel Deaconess Medical Center in Boston, has been a driving force in making ASCO focus on the costs and value of cancer care. His support of Kevorkian and assisted suicide legislation are relevant. Specifically, just as Schnipper believed that hastening death when further treatment could only add a few months of life was legitimate, the Task Force he leads asserts that a few months or weeks of life have no clinical value and that further treatment is a waste of money at that point.
In 1998 Schnipper was part of “a high-powered collection of area doctors, academics and lawyers has been meeting privately, working to draft a model bill allowing physician-assisted suicide. "We'd like to get this bill introduced in Massachusetts and elsewhere," says Boston College law professor Charles H. Baron.
The group includes James Vorenberg, former dean of Harvard Law School; Judy Johnson, associate general counsel at the New England Medical Center; Dr. Lowell Schnipper, chief of oncology at Beth Israel Hospital; and Dr. Sydney Wanzer of the Harvard Law School health services. Most of the 10 members, says Baron, support legalization "in the hopes that this will make relief from suffering more readily available and in a less discriminatory fashion and with greater patient autonomy."
Schnipper’s Working Group Supported Dr. Jack Kevorkian
Dr. Wanzer noted: "If Dr. Kevorkian does it a little outside the niceties of proper practice, I can't condemn him for that. If I do this privately and quietly and discreetly, it doesn't force the issue. But he does. I think it's a good combination of the quiet people who go ahead and do what they think is right and the Dr. Kevorkians who do it more flamboyantly."
"Kevorkian is a result of failures of our medical system in caring for someone with intractable or chronic problems," says Dr. Lowell Schnipper, chief of cancer treatment at Boston's Beth Israel Deaconess Medical Center. "But Kevorkian is becoming more and more marginalized as legitimate groups begin to weigh in with the resources and sensitivities the problem demands, which to me is good news."
Schnipper also described hastening death as "consistent with the highest goals of the physician as healer and must be an option in a pluralistic society."
Today Schnipper Believes Cancer Treatment That Adds ‘Only’ Three Months of Life is Not Worth It.
In 2010 Schnipper was the lead author of an article that argued:
“Patients' high expectations of cancer therapy may be another cost driver
In a culture that favors treatment and has an overly optimistic view of what medicine can offer, it is an uphill battle for cost-conscious oncologists to communicate the true value of various forms of therapies, particularly when curative treatment options are lacking.”
He also notes:
“This problem may be particularly American one; other cultures do not seem to view the postponement of death by a few months as holding an equivalent importance. Culturally, are we entirely honest in our assessment of what a few months, particularly spent in illness, can accomplish?”
Value Framework Also Embraces Notion That A Few Months More Of Life Is Not Worth It
Schnipper, writing for the Task Force concludes:
“Cancer drug spending is being driven by “sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.”
Patients “ also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all.
Schnipper Established A Cut Off Point For Value Measured By a 20 percent increase (3 months) in yearly survival
Over the past two decades Schnipper has advanced an economic argument for cutting off cancer treatments. Initially, he maintained that survival time should be increased beyond a specified amount of time:
“On average they (cancer treatments) may delay death for only a very short time, for example 3 months. Although some patients may live for more than 3 months, others will not necessarily live even that long. The drug only slows the progression of the patient's cancer by a few months; it does not “cure” the cancer. The psychological force of the rule of rescue should be much weaker in the context of this cancer care than in mine collapses. It should not make it impossible to resist providing the treatment, and certainly does not justify doing so. “ (In this regard, applying Schnipper's logic to everyone means stopping treatment for every patient that does not gain more than 3 months on average, including babies, HIV patients and children with rare diseases. )
The Task Force Cutoff for Value Is The Same As Schnipper’s
Under his leadership of the Value Task Force, the 3 month cut off was turned in to a specific increase in survival as a percentage of a year of life: “It was generally agreed that relative improvements in median overall survival of at least 20% are necessary to define a clinically meaningful improvement in outcome. “ On average, 20 percent ranges from weeks to a few months. This is a value judgment that applies to all patients with all forms of cancers with all different tumor types.
Schnipper believes that below a certain increase in survival money spent on dying cancer patients should be spent elsewhere to ensure resources are distribution ‘fairly.’
He claims: “The result of abandoning reasonable value standards in the face of urgency would be the use of much very high-cost, marginal-benefit care for dying patients. This situation is arguably our current practice in much care, including cancer care, of dying patients. But it is neither a rational nor ethical use of limited resources. The money spent on this very expensive, but marginal benefit, end-of-life care, could produce greater benefits if spent elsewhere either within or outside the health care system.
Schnipper goes on to state a cut off level:
“A cancer treatment that postpones death on average for 3 months at a cost of $100,000 does not produce…a large benefit. The opportunity costs of securing that treatment are much too great.”
Schnipper has argued that spending on overage increase of three months comes at the expense of other uses of money.
“A life-saving treatment like an appendectomy generally produces a very large benefit; it prevents the patient's death and returns him or her to a healthy life. But a cancer treatment that postpones death on average for 3 months at a cost of $100,000 does not produce such a large benefit. The life extension is short, and the quality of life during it is often poor. It is not a large enough benefit to trump the greater benefits to many that would have to be foregone to provide it.”
Similarly, the Value Framework declares:
“Oncologists should be aware of the value of an intervention in terms of societal cost. Clearly, increasing health care costs are eventually transferred to the consumers of health care, if not in the form of out-of-pocket costs, then in the form of higher insurance premiums, higher taxes, or limited wage increases as employers confront the escalating costs of providing health care to their employees."
What Schnipper and The Task Force Ignore
The task force asserts that spending on new cancer drugs bankrupts individuals and our healthcare system. But the benefits to patients are palpable. Drugs that emancipate our immune system to attack tumors or target specific genetic cancer causing mutations have transformed cancer care. These cancer drugs are expensive no doubt. Yet they account for only account for 0.7 percent of the $2.9 trillion we spend on health care. Cancer spending has increased in 1995 from $42 billion to about $130 billion today. But its share of total health spending declined from 4.7 percent to 4.4 percent during the same time period.
New medicines reduce the cost incurred by a cancer diagnosis, for instance in part by reducing hospitalization. In 1996 drugs were 3.7 percent of cancer spending and 62.4 percent went to hospitalization. By 2012, drug spending was 9.3 percent of cancer costs while the share going to hospital stays dropped to 41.3 percent. If we were allocating the same proportion of money to hospitals today, as we were in 1996, we’d be spending about $18 billion more a year on cancer. And we have yet to see the full benefit of the cancer drugs not yet included in these estimates.
As the price and number of new treatments increases, their value increases too. A recent Bureau of Economic Analysis study found between 2000-2010 that “medical technology (for treating cancer and other costly illnesses) is improving over time, leading to better health outcomes at a lower cost per patient.” A lot of that has to do with medicines displacing less effective and more costly oncology services. Why does the ASCO Value Task Force ignore that.
Between the time Schnipper was pushing for assisted suicide until the time that he has begun pushing to limit the use of cancer drugs for people with “only” three months to live cancer survivorship has surged from 10 million to 14 million people and life span expressed by 36 million life years worth about $3 trillion.
If Schnipper’s vision had become common practice how many of those survivors would not be alive today? How many will not live because of his current plans?
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