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Per a report in BioCentury, PatientsLikeMe Inc. has granted FDA access to its patient-reported data, which the agency said it will use to identify risks and benefits of drugs. The agency said PatientsLikeMe's adverse event data have the potential to supplement existing sources, including data that sponsors are obligated to report and data from FDA's Adverse Event Reporting System (FAERS), to address safety issues that arise postmarket. PatientsLikeMe said FDA will have access to more than 110,000 adverse event reports on 1,000 different drugs at no cost. The data include information on drug tolerance, adherence and quality of life. PatientsLikeMe President Ben Heywood told BioCentury the collaboration "may lead to FDA-sponsored research projects designed to understand how patient-reported data might be used to enhance post-market surveillance, support regulatory decision making and inform regulatory science." FDA also operates the Sentinel system, with which it can query electronic health records to identify and monitor postmarket safety concerns.Read More & Comment...
From the pages of the Houston Chronicle:
Pitts: Obama's drug crusade comes at high price
Medicare Part D program, which provides affordable drug insurance, needs to be emulated, not reformed
A new federal report misleadingly estimates the cost of the Medicare Part D program at $103 billion. That figure is bunk. Nonetheless, it will give President Barack Obama more ammunition for his assault on Part D - a program that provides affordable prescription drug insurance to more than 2 million Texas seniors.
Already, the president has pushed for government controls on drug prices in Part D - a "reform" he endorsed in his 2016 budget.
But Part D doesn't need to be reformed - it needs to be emulated. The program is a historic success. Federal interference in Part D drug pricing would destroy that success and drive up the cost of medications, reduce enrollee choice, and harm patients.
Part D drug coverage is affordable for seniors and taxpayers alike. The average monthly premium for a Part D plan is around $32 - and hasn't changed much over the last five years.
Nearly a decade after Part D was created, the program's overall costs are almost $350 billion below initial estimates, according to the Congressional Budget Office.
Unsurprisingly, the program is enormously popular. Among beneficiaries, Part D's satisfaction rate is roughly 90 percent.
Yet the Obama administration wants to tamper with the program by bargaining directly with drug manufacturers for rebates on Medicare prescriptions.
Currently, the law that established Medicare Part D prohibits federal officials from interfering "with the negotiations between drug manufacturers and pharmacies and [prescription drug plan] sponsors."
The Obama administration views this lack of government negotiation as a shortcoming that boosts Part D's cost. But non-interference is actually essential to the program's success.
Indeed, the reason the program is able to deliver satisfactory coverage at such a reasonable cost is its competitive structure. Under Part D, Texas beneficiaries are free to choose from 32 different private coverage plans.
In order to win customers, plan providers compete with each other to offer the best policies at the lowest cost, driving down prices in the process.
This arrangement works because private insurers are able to secure their own drug rebates through private negotiations with pharmaceutical firms. These rebates frequently amount to a 20 or 30 percent discount. And those savings are passed on to beneficiaries.
If the federal government intrudes on private Part D negotiations, the competition driving the program's success will collapse. Drug prices will go up. Quality of plans will go down.
Worse, federal interference in the negotiations wouldn't result in lower drug prices, as the Obama administration claims. Researchers from the Congressional Budget Office have concluded that government officials "would be unable to negotiate prices across the broad range of covered Part D drugs that are more favorable" than the prices achieved by private insurers.
Unfortunately, the administration's rhetoric against Part D ignores these existing discounts. The $103 billion figure, which comes from a Center for Medicare and Medicaid Services report, doesn't account for the discounts either. CMS simply tallied up the market price of all drugs dispensed through Part D.
Factoring in those privately negotiated rebates paints a more accurate picture of Part D annual costs, which are closer to $62 billion.
Federal intervention won't lower Part D's total cost, but it will make it harder for seniors to get the medicines they need. According to Douglas Elmendorf, the former head of the Congressional Budget Office, negotiating for a lower drug price on a given drug carries "the threat of not allowing that drug to be prescribed." Beneficiaries could loss access to treatments they now depend on to stay healthy.
Sadly, none of these facts have stopped the Obama administration from trying to interfere in Part D price negotiations. But it's important to ask: What does the president hope to accomplish with his proposal?
If the president's aim is to expand access to affordable prescription drugs, he should be celebrating Part D - not trying to destroy it.
Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.Read More & Comment...
To that point, a new op-ed from today's edition of the Wall Street Journal.
The Patent Trial and Appeal Board was supposed to make the system better. It hasn’t.
BY: Peter J. Pitts
When Ultratec, a manufacturer of closed-captioned phones for the deaf, realized that a rival had created a knockoff using its patented technology, the company filed a patent-infringement lawsuit. A Wisconsin federal jury ruled for Ultratec in October, ordering rival Sorenson Communications to pay $44 million in damages.
But Ultratec may never receive a cent. In March a little-known but hugely powerful federal body called the Patent Trial and Appeal Board (PTAB) invalidated Ultratec’s patents, on grounds that the designs were too obvious to be patentable.
The PTAB, created by the 2011 America Invents Act, was intended to strengthen the patent system. Lawmakers hoped to avoid the need for patent lawsuits by giving patent holders and challengers a quick and inexpensive way to resolve disputes as an alternative to the courts.
But the board uses looser standards than a federal court to evaluate a patent’s legitimacy. Courts assume that a patent is valid until a challenger provides “clear and convincing” evidence to the contrary. The PTAB requires only that challengers show that it’s more likely than not (i.e., a “preponderance of the evidence”) that a patent is too broad.
In recent months the board has overturned patents on a computer memory technology, a popular videogame, and a system for monitoring car tires. The PTAB has invalidated at least one “claim”—or part—in almost 80% of the patents it has ruled on, according to a study in the University of Chicago Law Review. Some patent experts such as Randall Rader, former chief judge at the U.S. Court of Appeals for the Federal Circuit, have referred to the 300-odd administrative judges, attorneys and legal aids on the board as “patent death squads.”
Patent challengers have jumped at the chance to exploit the board’s lax standards. Since it began to operate in September 2012, the PTAB has received more than 2,600 patent challenge requests—three times more than it expected.
Many of these challenges—such as one against Combigan, an eye-drop medicine that prevents blindness in patients with glaucoma—seek to overturn patents that district courts have already upheld. In many other cases, the patents have also been challenged in federal courts—but courts have stayed the litigation until the PTAB has ruled. The patent may be invalidated without facing a court’s stricter standard.
The PTAB could devastate innovation-intensive industries. Consider pharmaceutical developers, which spend about $51 billion a year researching new treatments. But less than 12% of drugs that reach clinical trials ever make it to market.
Patents give firms the financial incentive to fund challenging research and development projects. In the event that a huge upfront investment results in a popular new product, the developer can recoup its costs in sales.
The PTAB jeopardizes this process. Since an overturned patent means that rival companies could create knockoff products, firms will lose the confidence that they’ll reap the rewards of innovation.
Some financiers have started using the PTAB to make a quick buck. Kyle Bass is a hedge-fund manager, not a pharmaceutical developer, but he recently challenged six drug patents. His strategy, which has been widely reported, is to bet that the challenges would drive down the patent owners’ stock prices.
The strategy is working. Early this year Mr. Bass challenged Acorda Therapeutics ’ patent on Ampyra, a medicine that uses a re-engineered bird poison to help multiple sclerosis patients walk. The claim: Medical experts would have been able to deduce the effectiveness and proper dosing of the re-engineered molecule. The challenge caused the company’s stock price to drop almost 10%.
If hedge funds and copycats continue to take advantage of the PTAB’s bias against patent holders, it will choke off funding for lifesaving medicines.
The Patent Trial and Appeal Board will make it harder to create the products that improve lives and fuel the economy. To avoid this dangerous outcome, Congress has to reform the PTAB so that it operates under the same standards as a regular court.
Mr. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest. Read More & Comment...
(Some animals are more equal than others.)
It's an important, timely, fun -- and a must read pre BIO and DIA.
Enjoy. Read More & Comment...
What does the FDA think of Amarin's plan for off-label communication?
Here's the letter the agency sent them. And, from the pages of the Wall Street Journal,the latest on Amarin's lawsuit and the FDA's counter-strategy.
FDA Tries to Blunt Amarin’s Free-Speech Lawsuit Over Off-Label Info
By Ed Silverman
Last month, a small drug maker called Amarin AMRN -4.82% caused a stir by filing a lawsuit against the FDA to argue that its right to distribute information about unapproved uses of a medicine is protected by the First Amendment.
Now, in an unusual move that appears designed to blunt the impact of the lawsuit, the FDA has written 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 the FDA suggests that Amarin might have known this if the drug maker had discussed the issue before filing its lawsuit.
The lawsuit is being closely watched for its potential to determine whether the FDA can prohibit drug makers from distributing off-label information. The issue has been widely debated after a federal appeals court in 2012 overturned a criminal conviction of a sales rep for promoting off-label uses. The court ruled his speech was protected, since the information was truthful and not misleading.
As we reported previously, Amarin wants to be able to provide doctors with information that does not directly pertain to the approved uses of its Vascepa prescription fish-oil pill. The FDA endorsed the drug to treat people with very high levels of triglycerides, a type of fat in the blood that can lead to heart disease.
But two months ago, the FDA rejected an Amarin bid to market its pill to patients with slightly lower triglyceride levels and denied its plan to add effectiveness data to the Vascepa product labeling. Amarin then filed its lawsuit, arguing it has a constitutional right to distribute the information, even though such a move would be considered by the FDA to be off-label promotion.
In its lawsuit, Amarin included a list of medical journal articles it would like to distribute to physicians. However, the FDA writes that none of these are problematic. The agency “does not have concerns with much of the information you proposed to communicate” and the FDA “would not consider the dissemination of most of that information to be false or misleading,” the FDA letter to Amarin states.
As it turns out, the FDA says that Amarin never approached the agency about the issue. In her letter, FDA official Janet Woodcock makes a point of writing that Amarin “did not ask for our views before filing” its lawsuit “as other pharmaceutical companies sometimes do.” A spokesman for Amarin says the drug maker would not comment.
Moreover, Woodcock also reiterated FDA plans to release a so-called industry guidance for governing the dissemination of off-label information. In effect, the letter amounted to a pre-emptive move that might slow the progress of the lawsuit, according to regulatory experts.
“I think Amarin is frustrated by the results of its dealings with FDA and has resorted to the courts instead of trying to maintain a constructive dialog with FDA,” says Ira Loss, senior health care analyst at Washington Analysis, a consulting firm. “Woodcock’s letter undercuts their case. Not talking to FDA before filing the suit will likely result in a summary judgment for the agency.”
Adds Peter Pitts, a former FDA associate commissioner for external affairs, who now does policy consulting for the pharmaceutical industry: “Amarin got some bad regulatory advice. The FDA has loudly signaled that it is going to act with increased regulatory discretion on off-label communications. This was either missed or ignored by Amarin.
“… A meeting with the agency would have addressed their concerns. [As for the FDA], “exercising regulatory discretion is a smart move as it takes the matter out of the hands of a judge. A free speech ruling would make things much more difficult for the agency. The FDA opted for strategic retreat rather than face a potential sledgehammer legal decision.”Read More & Comment...
Now, innovation is NOT invention. Here's Sir Harold Evans, another very smart person on this issue: innovation is bringing an invention to use (i.e. commercialising it)...a scientist will have understanding, an inventor will have a solution but an innovator will have a universal solution.
An invention without innovation is a past-time. Essentially, many inventors are hobbyists, since an MIT study has shown that fewer than 10% of patents granted have had any commercial application.
Evans says that few scientists are able to turn ideas into a commercial impact.
Which leads me to the NIH' foolish foray into drug development.
Innovation is about commercialization. Commercialization especially today requires something that is in large supply in the private sector and short supply at the NIH:
Experience in commercialization, which includes constantly learning from failure in the development of a product that one hope's will have mass appeal and consumption.
Further, as a Fast Company article notes: ln a world of rapid disruption, having a core competency—that is, an intrinsic set of skills required to thrive in certain markets—is an outmoded principle of business. Just as Google needed Android to attack mobile and Apple needed Siri to pursue search, thriving businesses need to constantly evolve, either through partnerships, new talent, acquisitions—or all three. Nike, No. 1 on Fast Company's 2013 list of Most Innovative Companies, proves this idea more than most. Last year, it launched FuelBand, a high-end electronic wristband that tracks your energy output and signaled Nike's growing strength in the digital realm. "Think about it: Nike is now included in conversations around technology—it's shifted into an adjacent industry, breaking out of apparel and into tech, data, and services," says Forrester Research analyst Sarah Rotman Epps. "That strategic shift is incredibly important to Nike's future."
NIH has been throwing little bits of money to keep up with the furious pace of evolution and the rapid shift of life science firms into related industries. It looks a little desperate but there's no choice because most of what NIH does and spends money on are discoveries and technologies developed outside it's walls.
Thus, while it was great to see that the NIH and FDA is looking for an entrepreneur in residence (for database analysis), I had to laugh since the idea of an entreprenuer locked inside government regulations and surrounded by people who's job longevity depends on avoidng risk and stifling others has the makings of a great comedy sketch.
Add to that the fact that entrepreneurs commercialize.. How can you do that when you have little experience scaling up clincal trials with safe and consistent and ample supplies of the materials you need to make something.
Ask people at the FDA what they think about the ability of NIH bureaucrats and researchers to engage in drug development. It's a good way to get them to laugh for a change.
I won't go into the demise of government run vaccine development facilties. I will mention that even before NIH contaminates samples that it is not very good at deciding what to develop or not.
Further, the NIH is horrible at clinical trial recruitment and management. Just ask cancer patients who on average wait 800 days for NIH sponsored trials to get up and running. Here's what Vince DiVita, the former head of the NCI said in 2008. Sadly, it is still relevant today.
"The requisite talent to know the right way to design and modify an ongoing study does not reside on remote review committees at the NCI or the FDA, yet those are the places where the delays are greatest. Too many cooks are spoiling the broth."
As John LaMattina points out When NIH was asking for funding for the National Center For Advancing Translational Science (NCATS) Dr. Roy Vagelos, the legendary former Merck CEO and now Chairman of the Board of Regeneron Pharmaceuticals. Testifying before the subcommittee as an adviser to the American Society for Biochemistry and Molecular Biology, he made the following point:
“Does anyone in the audience believe that there is something that NCATS is going to do that the industry thinks is critical and that they are not doing? That is incredible to think that. If you believe that you believe in fairies.”
In fact, what NIH has done has pull funding from the Molecular Libraries Program which supported has made a contribution to the development of drug discovery tools. These tools have, in the hands of Hugh Rosen, who runs a lab at Scripps, revolutionized drug discovery. Rosen's work only led to the development of biotech startup Receptos which has several drugs under development and as well as the development of a drug to control the cytokine storms that cause sudden death in people with the flu. So what did NIH do? It not only rejected future grant requests from MLP participants it pulled the money that would have supported improvements and next generation tools and it put it into the NCATS, the government's drug company. That's not what entrepreneurs do unless they want to waste money. As one advisor to the Molecular Library Program noted the kind of spinoff for which Receptos is the poster child is “something that has come from this and is probably going to disappear.”
Think of NIH as a $30 billion business that has strayed from it's core competency: funding outside the box research and ideas and supporting small groups of researchers who contribute to and interact with anyone that seems to be solving key research questions and wants to turn them into products. The way back is to democratize and de-routinize grant giving and break up the cartel of research centers that rely upon NIH money for overhead. Craig Venter's suggestion should be taken seriously:
"The academics might not like it, but peer review is like the prisoners running the prison. They're not going to vote for change. Universities like this system because it helps support the universities. We have to change it so that 25%, 30%, 40% of the money is set aside for true risk research with independent parties to do that. That's going to disrupt a lot of things. I argue that the American public should be outraged that there's not 10 times to 100 times more breakthroughs in medicine every year over what we're getting, particularly for the money that's being spent."
Congress is likely to increase NIH funding. Unfortunately, the influx of cash will go to waste without the kind of mission change Venter has suggested. Read More & Comment...
From the pages of the Orange County Register
The FDA has patients playing a dangerous name game
What's in a name? In medicine, it could be the difference between life and death.
A new class of drugs is coming onto the U.S. market. Unfortunately, Congress is standing by as the Food and Drug Administration prepares to allow marketers to sell these imitations under the same name as the original drug.
The only problem is that the drugs aren't the same. The differences between the drugs, although subtle, can have serious consequences for patients' health. Lawmakers should instruct regulators to acknowledge these differences by establishing a naming system that distinguishes between the knock-offs and the originals.
The new drugs are "biosimilars." They're inexact copies of biologics – a type of complex drugs derived from living cells. Because living cell strains can't be replicated exactly, the biosimilar drug grown from these cells is also impossible to copy exactly. They're similar, but not identical – and that's the problem.
Biosimilars produced by different manufacturers have similar properties but are not identical to the original or each other.
The medical field rightly values precision, and the ability to trace side effects back to a specific drug is a crucial patient right. To protect that right, Congress should instruct the FDA to develop a clear-cut naming system that calls different medications by different names.
A study conducted in Ireland revealed important distinctions between biosimilars and the biologics on which they were based. The study found variations when Inflectra, a biosimilar that treats rheumatoid arthritis and Crohn's disease, was tested against the biologic it tried to copy. While only 5 percent of patients who received the biologic required hospital readmission, 80 percent of the Inflectra group did.
In addition, just 8 percent of the biologic patients needed multiple bumps in steroid dosage for effective treatment, but 50 percent of Inflectra patients required them. The authors of the study concluded that biosimilars might be less effective than the original biologics.
The FDA itself noted that it's first-ever commercially approved biosimilar, Zarxio, has a lower protein content than filgrastim – the original biologic. The agency dismissed the difference as a manufacturing flaw. But because biosimilars don't undergo extensive clinical trials, drug defects or harmful side effects will be detected only after they enter the market. When side effects do occur, calling different drugs by the same name would subject patients to an impossible guessing game. Did Patient A take the original filgrastim or biosimilar Zarxio?
Fortunately, the FDA's naming system is trying to address this problem. The FDA is calling Zarxio "filgrastim-sndz."
That suffix, representing the drug's manufacturer name "Sandoz," is better than no distinction, but it's still problematic. That's because a suffix shouldn't be tied to the manufacturer's name.
If Sandoz changes its name, or merges with another drug company that makes its own knockoff version of filgrastim, the four letter suffix would lose all meaning. "Sndz" is not a clear-cut differentiator that would follow a drug from patient to patient, year to year. A constant alpha-numeric suffix like "aaa123" would be considerably more effective.
The FDA must recognize that Zarxio and filgrastim are different products and have different side effects. Common sense dictates they should have different names.
Congress and the FDA need to recognize this and implement a distinct naming system before patients get hurt. Zarxio and filgrastim are almost copies of each other. But giving them the same name is akin to almost healing a patient or finding almost the right diagnosis. It's just not good enough.
Peter J. Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest.Read More & Comment...
From FDA Law Blog:
Return of the Scarlet Letter? AbbVie Petitions FDA to Require Biosimilar Labeling to Include Disclaimers and a Description of Data Differences
It was just a few weeks ago that concerning FDA’s recently finalized guidance document on “” that the Agency removed from the of the document any requirement that the labeling of a biosimilar biological product licensed under PHS Act § 351(k) indicate that it is biosimilar to a reference product, and also to call out whether or not it is interchangeable with a reference product. As we commented then, “[w]hile such designations may not have made a biosimilar feel like Hester Prynne, it does seem that mandating such terms be present may have led to some shunning in the marketplace that is today’s town green.”
It seems that AbbVie Inc. (“AbbVie”) – which, interestingly, starts with the letter “A” – took note of the Scarlet Letter change as well. In a June 2, 2015 (Docket No. FDA-2015-P-2000) that popped up on regulations.gov earlier this afternoon (June 3rd), the company requests FDA to require the approved labeling for biological products licensed under PHS Act § 351(k) to contain (if applicable) certain statements and descriptions that would differentiate biosimilars from their reference product counterparts. Specifically, AbbVie wants biosimilar labeling to include:
A clear statement that the product is a biosimilar, that the biosimilar is licensed for fewer than all the reference product’s conditions of use (if applicable), and that the biosimilar’s licensed conditions of use were based on extrapolation (if applicable);
A clear statement that FDA has not determined that the biosimilar product is interchangeable with the reference product (if applicable); and
A concise description of the pertinent data developed to support licensure of the biosimilar, along with information adequate to enable prescribers to distinguish data derived from studies of the biosimilar from data derived from studies of the reference product.
Biosimilars, which came about with the March 23, 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“”), “are not generic drugs and should not be labeled like generic drugs,” says AbbVie in its petition. Including in biosimilar labeling the items above “is necessary to enable rational and informed prescribing decisions regarding these complex products, to avoid potentially unsafe substitution of biosimilars and reference products, and to combat widespread misconceptions among prescribers about biosimilars and their relationship to reference products,” writes the company. Furthermore, without such differentiating statements and description, “biosimilar labeling will not reflect the unique licensure provisions established by the BPCIA and will be materially misleading in violation of the FDCA and FDA regulations.” And, in what might be a signal of future litigation, AbbVie alleges that FDA’s “about-face” reversing, without explanation, what the Agency proposed in the 2012 draft guidance is a violation of the Administrative Procedure Act (“APA”). (Though, keep in mind that the last time Abbvie – then Abbott Laboratories – petitioned FDA on the BPCIA back in 2012 – concerning Reference Product Exclusivity – we though a lawsuit might be looming – see our previous post . That didn’t happen – at least it hasn’t yet.)
Pointing to FDA’s March 6, 2015 approval of for Sandoz Inc.’s (“Sandoz’s”) ZARXIO (filgrastim-sndz), a biosimilar version of Amgen Inc.’s NEUPOGEN (filgrastim), AbbVie says that FDA long ago made the decision to apply the “same labeling” requirement under FDCA § 505(j) (applicable to ANDAs) for small-molecule generic drugs to biosimilars licensed under PHS Act § 351(k):
Publicly available materials from FDA’s review of Zarxio confirm that FDA followed a “same labeling” approach. According to the action package for Zarxio, in November 2013, Sandoz proposed and FDA agreed that the biosimilar and reference product labeling “should be essentially the same.” In February 2015, FDA provided the labeling for Neupogen to Sandoz for use “as a template” in developing the labeling for Zarxio, and instructed Sandoz to track any changes made to the Neupogen labeling and provide annotations to explain and justify any such changes. That is essentially what FDA regulations require of applicants seeking to market generic drugs under section 505(j). Indeed, in the media briefing announcing the approval of Zarxio, the Director of the Office of New Drugs in the Center for Drug Evaluation and Research (CDER) acknowledged that the “approach” taken with respect to the labeling for Zarxio was “not that different from the approach . . . taken in the past . . . for generic applications.” Consistent with that approach, the approved labeling for Zarxio is nearly identical to that of Neupogen . . . .
According to AbbVie, however, applying the FDC Act’s ANDA “same labeling” approach to to biosimilars is legally unsound. AbbVie then ticks off the reasons why such an approach doesn’t comport with the law.
“First, a ‘same labeling’ approach is flatly inconsistent with the BPCIA, which—unlike the [ANDA] provisions in section 505(j)—includes no ‘same labeling’ requirement and recognizes that biosimilars are different from their reference products. . . .” (Emphasis in original). Here, AbbVie compares and contrasts the BPCIA and the FDC Act, noting, among other things, that the BPCIA specifically amended the FDC Act (at FDC Act § 505B, concerning required pediatric studies) to provide that a non-interchangeable biosimilar biological product “shall be considered to have a new active ingredient” (at least for purposes of FDC Act § 505B).
“Second, a ‘same labeling’ approach to biosimilars would result in labeling that omits material information necessary for safe and informed prescribing, and would exacerbate, rather than dispel, misconceptions among prescribers regarding biosimilars.” Here, AbbVie argues that applying a “same labeling” approach to biosimilars violates the FDC Act’s misbranding and misleading labeling provisions at FDC Act §§ 502(a) and 201(m), respectively.
Third, AbbVie argues that “FDA has not provided the reasoned explanation required by the APA for its decision to abandon the approach taken in the Draft Scientific Guidance, which stated that the labeling of a biosimilar product should disclose that the product is a biosimilar, the scope of its approval, and whether it has been found to be interchangeable, on the ground that this information is ‘necessary’ for informed prescribing.” Going through the record of FDA meetings and comments leading up to and on the draft guidance, AbbVie asserts that “FDA’s decision to reverse course and adopt a same labeling approach for biosimilars is arbitrary and capricious.”AbbVie’s petition includes a certification under FDC Act § 505(q), which was made applicable to petitions affecting pending Section 351(k) biosimilar applications under the 2012 FDA Safety and Innovation Act. This is, by our count, the second citizen petition involving the BPCIA containing such a certification. FDA denied the first 505(q) biosimilar petition earlier this year (see our previous posts and ). If FDA tags AbbVie’s petition as a 505(q) petition – which seems probably given the likley pending status of Section 351(k) applications at FDA that could be affected by the petition – then we can expect some sort of response within 150 day Read More & Comment...
It is true that out of pocket costs discourage use and force many to choose between food and medicine. The culprits in this instance are health plans and pbms that have increased cost sharing on new drugs by thousands.
AARP -- being an insurer as well -- participates in this immoral activity. The claim that drug prices and drug costs drive up premiums -- including those of AARP -- is false. New medicines for life threatening illnesses are less than 2 percent of total health spending. A Milliman study concluded it would cost about 50 cents per person to cap copays at $250 a year.
So instead of just publishing studies about drug prices, AARP should do the right thing and close the co-pay gap.
Read More & Comment...
Going to BIO? Join me on June 16th for “Public Sector Biotech Initiatives in Middle East and North Africa. I’ll be moderating a panel of experts and government officials discussing government and public sector initiatives designed to attract biotech research and development in the MENA region. We’ll discuss tax incentives, regulatory, reimbursement and IP policies as well as government investments that key MENA countries have implemented to attract biotech companies.
And here are the details:
WHEN: June 16, 2015, 3:30 PM–4:45 PM
WHERE: Room 119A
Marwan Abdulaziz Janahi, Executive Director of Dubai Biotechnology and Research Park (DuBiotech)
Samir Khalil, Executive Director of Middle East & Africa, PhRMA
Tarek Salman, Assistant Minister of Health and Population for Pharmaceutical Affairs in Egypt
David Torstensson, Senior Consultant, Pugatch Consilium
Jeffrey Kemprecos, Executive Director,Emerging Markets Public Policy, Merck
Peter J. Pitts (Moderator), President, Center for Medicine in the Public Interest
Hope to see you there.
The WSJ gave a lot of coverage to Leonard Saltz vitriolic attack on the cost of new immunotherapies for cancer. Saltz call the prices for immunotherapy for advanced melanoma insance and immoral, some the WSJ article: High Prices for Drugs Attacked at Meeting
Cancer specialist criticizes new-treatment costs in high-profile speech
Dr. Leonard Saltz bases his fear about the unsustainability of cancer drug costs on emotion, not fact. He claims that if we treated everyone with metastatic forms of cancer with treatments costing $295000, we would spend $174 million each year and that cost would be unsustainable.
Actually, it would be a bargain. Dr. Saltz is assuming everyone who dies of cancer each year (580000) would get a combination of immune therapies. The combination in question -- nivolumab (Opdivo) and ipilimumab (Yervoy) adds about a year of life to people with advanced forms of cancer. So let’s stick with melanoma in explaining the incredible amount of value generated and money saved by such therapies.
The most recent estimate of the direct cost of treating advanced melanoma is $160,000 per person. (The direct costs of treating metastatic colorectal, breast and lung cancer are about the same.) A good portion of this cost would be eliminated by using immunotherapy because the treatments displace the use of existing medicines and hospitalization. I don’t count the amount of money saved from avoiding surgeries to remove tumor masses since the immune therapy shrinks tumors by 80 percent. But if we treat everyone with such therapies in end stage cancers, we could save $92 billion a year on less effective forms of treatment.
Further, stage IV melanoma currently has two-year survival rate of only 15 percent when treated with conventional chemotherapy. Immune therapies allow 90 percent of patients to live 2 years.
If we assume that 90 percent of people who otherwise die of cancer in a given year lived two years that would add 1.1 million life years for each group of patients. An early study estimates the productivity loss of cancer death at about $250 billion. Thus adding 1 million life years would generate $500 billion. A more conservative estimate (valuing an additional life year at $150000) would be $150 billion. And even if we assume a 60 percent response rate under either scenario, our society more than breaks even with a jump in two year survival. Of course, if 90 percent of people who live two years, wind up living 5 years, both savings in medical spending and life year value soar.
Dr. Saltz said cancer drug prices are insane and immoral. I’d say the same about someone who said – given these benefits – we shouldn’t perhaps pay even a little more. Read More & Comment...
From the pages of Politico …
21st Century Cures up against FDA’s 20th century communication
When it comes to communication, the 21st Century Cures Act is stuck in the 20th century.
The sweeping biomedical innovation bill aims to speed up development of medical treatments by taking advantage of the latest in science and technology. But provisions meant to update the FDA’s regulations on drug advertising were dropped.
The agency’s current marketing and promotion regulations don’t even mention the Internet. They focus instead on brochures, file cards and, inexplicably, lantern slides — a mid-1800s invention that was supplanted decades ago.
In the era of Facebook, Twitter and YouTube, drug and medical device makers contend a social media reboot is critical.
The first draft of the House Energy and Commerce’s bill did make an attempt. Among other changes, it would have forced the FDA to let drug companies communicate truthful “introductory” information in character-limited settings such as Twitter so long as they hyperlinked to a webpage with more safety and efficacy information.
That “one-click” concept is gone from the legislation that cleared the committee on May 21 and is now headed to the House floor. Also gone is a measure directing FDA to revise all regulations and guidances that could apply to online communications so that drug and medical device makers can use the Internet “in a meaningful way” to disseminate truthful and non-misleading information.
In Rep. Billy Long’s view, these provisions would push FDA “to update its regulatory approach to communications to keep up with today’s technology.” The Missouri Republican quickly introduced them as a separate bill after they were cut from Cures, and an E&C staffer signaled late Friday that members remain supportive and that more work could take place later this year on proposals that didn’t garner a bipartisan consensus before the committee’s vote.
The social media debate involving FDA, the pharmaceutical industry and Congress is taking place in what is quickly becoming a free speech powder keg. Companies are pushing the agency to align its policies with recent court decisions that have upheld their right to communicate certain information regardless of whether it appears on an FDA-approved product label — the regulatory standard for what is widely marketable.
Without faster change, the industry warns, FDA instead risks a complete overhaul of its advertising and promotional regulations by the courts.
Richard Samp, chief counsel at the nonprofit Washington Legal Foundation, which defends the free enterprise system as its mission, has worked for decades on these issues. Though he doesn’t foresee the courts taking over FDA’s authority to set limits on pharmaceutical marketing, he does expect continued legal challenges that could complicate the regulatory environment.
“FDA has been on a pretty long losing streak when it comes to First Amendment issues, and the longer FDA continues to do nothing, the longer it will be that they continue to have these losses and the more confusion that will be created,” he said.
The agency should see the Internet as unique from older, static forms of communication, drug makers argue.
“Right now, FDA essentially treats a web page or even a banner ad or a tweet as if it were a print vehicle, when patients and health care professionals who are online treat the Internet differently,” said Jeff Francer, vice president and senior counsel at the Pharmaceutical Research and Manufacturers of America.
Unlike a print ad, the web allows a company to constantly update information. It also lets consumers quickly jump from one page to additional product details or third-party content, and companies want to know how much they’re on the hook if a third-party site later adds information about a drug’s unapproved use.
Social media triggers other scenarios. Companies say they need more guidance on when they must report adverse drug experiences patients share with them through a posting on their Facebook page, for example.
At the same time, FDA is itself engaging online — in ways that only accentuate the gap between its lack of guidance for industry, critics say.
While the agency uses Facebook and Twitter to make short announcements on medical products, companies that do the same risk legal repercussions for not including enough risk and efficacy specifics in their post. Even retweeting the FDA’s own communication would be in violation of the agency’s advertising policies.
“The FDA uses Twitter to link its announcements to more comprehensive information. It is commonsense for the federal government to allow drug manufacturers to use these platforms in a similar fashion,” Long told POLITICO.
FDA first held a public meeting to discuss promotion of agency-regulated products on the Internet nearly two decades ago. Joy Liu, who specializes in drug advertising and promotion at the Washington law firm Ropes & Gray, remembers officials discussing the use of chat rooms and news groups, “sort of a precursor” to social media, she said.
But that 1996 meeting failed to translate into substantial policy changes. In 2009, Liu said, the agency reconvened another public meeting, asking how drug makers could fairly balance benefit and risk information for consumers, how they could embed hyperlinks and how they should correct inaccurate information on the Internet about a product.
Not until last year, however, in response to the FDA Safety and Innovation Act of 2012, did the agency release a pair of Internet-specific draft guidances.
“Is this as important as curing cancer? Maybe not, but it is I think important,” Liu said. “Getting information out about your products, understanding what are the rules of the road, have become critical to companies because they have been prosecuted for allegedly doing the wrong thing.”
Others maintain that the FDA has given industry sufficient direction. The agency’s former associate commissioner for external relations, Peter Pitts, says its current guidance on the Internet and social media is fairly good — but that industry has chosen not to pay attention.
“I think it’s a bit of an excuse for industry not to engage,” he said, adding that companies may find it “very frightening” to take part in such immediate, two-way communication with consumers and do the 24/7 monitoring that social media can require. “It takes guts and chutzpah” to engage online, Pitts said.
FDA did not respond directly to a question about its pace in adapting advertising regulations to evolving technology, instead highlighting its two recent guidances and the projected release of further regulations this year.
“FDA sees social media as an important resource for industry and is committed to developing additional guidance for drug and device manufacturers that outline the agency’s current thinking,” a spokesperson said. “We do all of this work with the best interest of patients in mind.”
The 21st Century Cures bill does expand what industry can say about its products when communicating with health insurers and asks for FDA to issue specific guidance on communication related to a drug’s off-label use.
Yet even as the 2014 draft documents make their way forward, the technology continues to evolve and trigger new questions, said Mark Senak, a lawyer who focuses on pharmaceutical and device marketing at the communications firm FleishmanHillard.
For instance, given that many people use a cell phone as their primary means for accessing the Internet, do companies have to make sure any website advertising is optimized for a mobile device? Senak says it is unclear whether a site that’s fully compliant with FDA regulations when it appears on a larger computer screen could face FDA enforcement because of how mandated information displays differently, and perhaps far less accessibly, on a small device.
One of FDA’s hurdles is that “they are an organization that’s really into understanding data,” Senak said. FDA wants to fully research an issue in a scientific manner before creating policy. “The whole process of them issuing a guidance document is just too slow for this environment.”
FDA’s drug center director, Janet Woodcock, testified at an April 30 congressional hearing on the 21st Century Cures legislation that the difference between FDA’s social media use and what industry is permitted to do stems from the different stakes each has — one is a government public health entity, the other markets drugs for profit.
What Woodcock didn’t note is how flexible FDA already is on direct-to-consumer drug advertising compared to the rest of the world. New Zealand is the only other country that allows drug companies to directly market to consumers.
There’s little chance that the U.S. public will stop using the Internet as a go-to resource on health concerns. According to a 2012 Pew survey, 72 percent of Internet users said they had looked online for health information within the past year. Much of that info is unregulated, a reality that also frustrates drug manufacturers.
Aaron Kesselheim, an associate professor of medicine at Harvard University, says FDA’s slow approach to releasing Internet and social media policy may be due to industry’s response to its past guidances on drug and device promotion.
After the agency issued guidance on print media in the 1980s, “investment in print media advertisement exploded,” Kesselheim said. The same thing happened after FDA put out guidance on broadcast media in the late 1990s, revising the parameters on the risk information companies had to include in TV ads. Virtually overnight, direct-to-consumer advertising spiked. It went from $579 million in 1996 to $1.3 billion in 1998. A decade later, it had again more than doubled to over $4 billion.
“You can understand why the FDA may be wanting to cover all of the bases … and is being deliberative about this,” Kesselheim said. “When these kinds of guidance do come out, they lead to a substantial expansion of advertising — which can have bad outcomes for patients because some drug companies take advantage of it.”Read More & Comment...
The latest post by Tracy Staton -- essentially a rewrite of an Express Scripts blog complaining about the cost of medicines -- lives up to that proud journalistic heritage. Staton once again obsesses about the amount of money spent on two or three cancer drugs without mentioning their impact. I think it’s because no matter the value of such innovative medicines, the profits and prices are too high for Staton.
"As the American Society of Clinical Oncology meeting approaches, the pharmacy benefits manager released some numbers on cancer drug spending. The top line? Spending on cancer meds grew by more than one-fifth last year, with a 9% increase in use and almost 12% increase in prices.
Prime suspects for that increase? The leukemia treatment Gleevec, from Novartis ($NVS), which boasts the biggest share of the market at 12.5%. Fellow blood cancer treatment Revlimid--the multiple myeloma therapy from Celgene ($CELG)--came in close behind with 10.8% of pharmacy benefit spending.
She will never be convinced. "
Let's take a look at those prime suspects and what they are guilty of.
All Gleevec did was launch a revolution in personalized medicine and an array of medicines that allow people with CML to live full lives. According to my colleague Tomas Philipson and his research group: The TKI drug class in CML therapy has created more than $143 billion in social value. Approximately 90% of this value is retained by patients and society, while approximately 10% is recouped by drug companies...
The introduction of TKI drugs to treat CML has generated significant social value as a result of survival gains, the vast majority of which has accrued to patients.
What about treatments for multiple myeloma developed by Celgene, Takeda and others since 1998:
Frank LIchtenberg concluded:
"(A)lmost two-thirds (0.99 years) of the 1997-2005 increase in the life expectancy of American myeloma patients was due to an increase in the number of chemotherapy regimens now preferred by specialists. Based on a back-of-the-envelope calculation, this means that the cost per US life-year gained from post-1997 chemotherapy innovation is unlikely to have exceeded $46,000. We also investigate the impact of chemotherapy innovation on the myeloma mortality rate using longitudinal country-level data on 38 countries during the period 2002-2012. Countries that had larger increases in the number of chemotherapy regimens now preferred by specialists had larger subsequent declines in myeloma mortality rates, controlling for myeloma incidence.
Put another way, people with myeloma added 360,000 life years since 1997, worth about $54 billion.
Finally, Staton ignores the contribtuion of cancer drug spending on total health expenditures.
As the amount spent on new medicines increases, the cost of treating such diseases has declined
In 2011, 11.4 percent of total cancer expenditures were for prescription medicines as compared with 3.6 percent in 2001
The proportion spent on inpatient hospital stays declined from 47 percent in 2001 to 35 percent I 2011.
Cancer spending as a percent of total health care spending and GDP actually has declined. Prescription drugs as a percent of total health care spending has remained at about 9 percent since 2000 and is projected to remain 9 percent for the next decade. All the while cancer drugs make up more and more of spending on drugs and cancer care.
So maybe the takeaway is that more spending on the newest and most expensive drugs is a good thing.. or at least not portrayed as a criminal activity by FiercePharma.
Fierce Pharma has to decide whether it has a responsibility to correct her bias by including other viewpoints or by providing greater editorial direction to include information that places the price and cost of medicines for cancer and other life threatening or disabling diseases in context.
My bet is that it will continue to demagogue an issue short on facts and chock fill of misplaced anger.
Read More & Comment...
NOTICE OF MEETING
Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee
The meeting will be held on July 7, 2015, from 8 a.m. to 5 p.m. and July 8, 2015, from 8 a.m. to 4:30 p.m.
FDA White Oak Campus, 10903 New Hampshire Ave., Building 31 Conference Center, the Great Room (rm. 1503), Silver Spring, MD 20993-0002.
The committees will discuss the results of post-marketing studies evaluating the misuse and/or abuse of reformulated OXYCONTIN (oxycodone hydrochloride) extended-release tablets, supplemental new drug application (sNDA) 022272, manufactured by Purdue Pharma L.P. The committees will discuss whether these studies have demonstrated that the reformulated OXYCONTIN product has had a meaningful impact on abuse of OXYCONTIN.
FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Background material is available at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee meeting link.
And most importantly
Persons attending FDA's advisory committee meetings are advised that the Agency is not responsible for providing access to electrical outlets.
The complete notice can be found here.
For example ESB would pay 5 times less to treat someone with pancreatic cancer with Tarceva than it does to treat lung cancer because the average survival benefit is less. ($1556 monthly compared to $6292)
My guess is that ESB would use $1556 as the reference price which means than any other company working on pancreatic cancer would see their good deeds penalized.
Similarly, ESB would price Erbitux for locally advanced squamous cell carcinoma of the head and neck at $10319 while it would pay only $471 for the much hard to treat metastatic forms.
That is not only economically peverse, it's immoral. If ASCO embraces this approach with it's value app it will kill innovation in cancer care overnight. There is still a lot of chatter from ASCO about paying for value, but also paying doctors more for using cheaper drugs.
This is disturbing. Lowell Schnipper,MD who runs the ASCO Value app project has made it clear that one goal of the app is to push down drug prices. And from Schnipper has said previously, the ESB pricing scheme is something he wants oncologists to endorse and discuss with patients. “My guess is that something like this can have a modulating effect,” he said. The increased transparency may make it more difficult for pharmaceutical companies to attach significantly higher price tags to drugs that confer only a small benefit.
Read More & Comment...
Those hot TV lights must be affecting Mike Huckabee’s cognition or, di minimis, his awareness of sloppy staff work.
"Americans should have the freedom to purchase safe drugs from Canada," Huckabee wrote in the Orlando Sentinel. "It just makes sense."
Let’s start here – there is a difference between the high quality, well regulated medicines Canadians get from their local pharmacies and those products sold to Americans via wildcat Canadian internet pharmacies.
Canadian internet pharmacies -- by their own admission -- are sourcing their drugs from the European Union. And while they may say their drugs come from the United Kingdom, let's not conveniently forget that 20 percent of all the medicines sold in the UK are parallel imported from other nations in the EU -- like Spain, Greece, Portugal and Lithuania.
Recently EU officials seized over 34 million fake pills in just two months. Irish drug enforcers confiscated over 1.7 million pounds of counterfeit and illegal drug packages. So if American customers start buying drugs over the Internet from Canadian pharmacies, they could easily wind up with tainted medicines of unknown European origin.
It’s also important to note that drugs from anywhere in Europe aren’t even legal for sale in Canada. So, when politicians say we can get “the same drugs” that Canadians get, they’re just plain wrong.
Even more worrisome is outright fraud — many “Canadian” pharmacies are actually headquartered somewhere else.
A 2005 investigation by the Food and Drug Administration looked at 4,000 drug shipments coming into the United States. Almost half of them claimed to be from Canada. Of those, a full 85 percent were actually from countries such as India, Vanuatu, and Costa Rica.
As part of another investigation, FDA officials bought three popular drugs from two Internet pharmacies claiming to be “located in, and operated out of, Canada.” Both websites had Canadian flags on their websites. Yet neither the pharmacies nor the drugs were actually from Canada.
As an FDA official told Congress, “We determined there is no evidence that the dispensers of the drugs or the drugs themselves are Canadian. The registrants, technical contacts, and billing contacts for both web sites have addresses in China. The reordering website for both purchases and its registrant, technical contact, and billing contact have addresses in Belize. The drugs were shipped from Texas, with a customer service and return address in Florida.”
And in laboratory analysis, every pill failed basic purity and potency tests.
The on-the-ground reality of state and local importation schemes have been dismal and politically embarrassing. Remember Illinois' high profile "I-Save-RX" program? Over 19 months of operation, a grand total of 3,689 Illinois residents used the program—which equals approximately .02 percent of the population.
And what of Minnesota's RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That's for the whole state. Minnesota population: 5,167,101.
Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well the city of Springfield has been out of the “drugs from Canada business” since August 2006.
And, speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”
The Canadian supplier for the program, Winnipeg-based Total Care Pharmacy, sent a letter to city officials saying the firm was terminating its agreement because there were so few participants. In 2006, Boston saved $4,300 on a total of 73 prescriptions. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.
And such programs won't do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation's spending on prescription medicines a whopping 0.1 percent—and that's not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally mentioned in foreign drug importation schemes.
Calling foreign drug importation “re-importation” is a clever way to sell the idea to the American people. But the term simply doesn’t fit with the facts. In reality, Americans would end up jeopardizing their health by purchasing unsafe drugs made in foreign countries – while not saving money.
Note to Governor Huckabee – Get better staff.Read More & Comment...
Yesterday the WSJ ran an article about how Express Scripts wants to tie the cost of cancer drugs to how well they work.
Let's deal with how hypocritical and self-serving this ploy is.
1. Health outcomes are a function of adherence to medication. Why doesn't Express Scripts tie what it makes in rebates to how well they help keep people on medicines. To do this, it would have to eliminate cost sharing for specialty medicines that are shown to discourage compliance.
2. Health outcomes are a function of getting the right medicine at the right time as soon as possible. Why doesn't Express Scripts invest in precision medicine profiling and eliminate cost sharing for medicines that are best for patients? Why doesn't Express Scripts refund copays when drugs dont work under a fail first or step therapy approach?
The answer: all this would get in the way of their profits. Discrimination against sick people by designing benefits in way that put all meds in the highest cost sharing tier is good for business.
Next, what about the feasbility and clinical impact of the Express Scripts proposal to tie payment to impact in specific uses or indications. The company borrowed this idea from Peter Bach who has been noodling about ways to control drug prices for years.
"Express Scripts’ approach would be similar to that proposed by Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center.In an article published last year in the Journal of the American Medical Association, he suggested that in an indication-specific arrangement, the monthly price for Eli Lilly & Co.’s cancer drug Erbitux (cetuximab) would plummet from $10,320 a patient to about $470 a patient for its least effective use, treating recurrent or metastatic head and neck cancer. The drug also is used to treat locally advanced head and neck cancer, as well as colorectal cancer."
So let's look at how this would work. Not only does Express Scripts want to do use the Bach approach, the Amercican Society for Clinical Oncology wants to use the it in telling cancer doctors what medicines.
Bach claims that the use of Erbitux for head and neck cancer is a "least effective use". Let's set side the curious math used to arrive at the $470 figure. It is more important to note that Bach ignores not only individual differences in response but the impact of Erbitux relative to existing need and treatment protocols. Bach uses an average 2.3 months more of survival as his benchmark. The price controllers love to focus on that number because it sounds so small. Express Scripts and Bach dishonestly ignore context.
Here's what we know about pre-Erbitux treatment of recurrent, metastatic squamous cell carcinoma of the head and neck (SCCHN):
"None of the trials performed in the past, even those with a reasonable sample size, have shown that aggressive platinum-based combination chemotherapy leads to survival benefit when compared to single agent methotrexate, cisplatin or 5-fluorouracil.
What difference does Erbitux makes?
After decades without real progress, a recent European randomized trial showed that adding cetuximab, the first clinically available EGFR-directed monoclonal antibody, to a standard chemotherapy regimen (platinum/5-fluorouracil) leads to an important survival benefit and this, with support of an additional smaller study in the US, has changed practice." J. B. Vermorken and P. Specenier Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol (2010) 21 (suppl 7): vii252-vii261 doi:10.1093/annonc/mdq453
Hence, the Bach-Express pricing approach would whittle away payment for the hardest to treat cancers for patients that have had no real advances in care for decades. Maybe Bach supports paying doctors less for people who are the farthest gone because the relative health gains are well, not worth it??
Second, the use of Erbitux, which targets the overexpression of EFGR associated with poor outcomes in SCCHN has lead to the development of biomarkers that that identify individuals that will have 4 times greater survival than the one size fits all studies Bach and Express Scripts would use to price treatment
Thanks to research done with the drug, we now have assays measuring evidence that Hypermethylation of the p16 gene is associated with KRAS mutation and response to Erbitux .
So now we have groups of patients that Patients with p16-unmethylated tumors had significantly longer time to progression (TTP, median 9.0 vs 3.5 month; and overall survival (OS, median 44.9 vs 16.4 months than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy had markedly shortened TTP (median 2.8 months) compared to those with either KRAS or p16 aberrancy ... Cancer Res Treat. 2015 Apr 24. doi: 10.4143/crt.2014.314. [Epub ahead of print] p16 Hypermethylation and KRAS Mutation are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with mCRC.
Kim SH1, Park KH2, Shin SJ3, Lee KY4, Kim TI3, Kim NK4, Rha SY3, Roh JK3, Ahn JB2.
In the studya above, hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) which means an even smaller group of patients then the number of patients in one size fits all studies. Following the Express Scripts logic, using a drug for a smaller group of patients that have had no progress in treatments and limited 5 year survival prospects should be priced LESS than $470.
Heaven forbid looking at the effect of 'even' 3 months of survival -- or 25 months of survival in a small subgroup -- this way:
Each year 60000 people are diagnosed with head and neck cancer each year. Fifty three percent have recurrent metastatic types.
Running the numbers for the 28.6 percent of high responders with metastatic (31800 x.286=17160) we get 20008 years of additional life worth $3.01 billion.
For the benefit, Express Scripts and Bach would pay $17 million. Meaning that they think an additional year of life for such patients isn't worth more than $583.
I didn't get into how patients receiving Erbitux spend about 30 fewer days hospitalized or in nursing homes and hospice. Or that total costs per treatment is lower with Erbitux. I don't have the time or patience right now to walk people who don't care or don't want to know through the economics.
Too bad no one in the media has run the math instead of running with this as a novel way to deal with health care costs. This is madness. As Isaiah Berlin put it, ‘disregard for the preferences and interests of individuals alive today in order to pursue some distant social goal that their rulers have claimed is their duty to promote has been a common cause of misery for people throughout the ages.”
Considering the paucity of biosimilar-specific data on the label for Sandoz’s filgrastim-sndz biosimilar, should sponsors be able to discuss their products’ analytical and clinical data with health care providers and payers? And what about with physicians?
When it comes to biosimilars, is off-label now on the table?
Zarxio was approved with labeling that was almost identical to that of Neupogen except for some differences specific to the products’ formulation and presentations The Zarxio label contains all of the same clinical data as that found in Neupogen labeling but none of the clinical or analytical data that supported the finding of biosimilarity to the reference product. But neither the word “biosimilar” nor the name of the reference product are found on Zarxio’s labeling.
Here’s the rub – the FDA has posted on its website hundreds of pages of review documents detailing its findings that Zarxio is highly similar to Neupogen with no clinically meaningful differences. However, the data analyzed in those reviews is nowhere to be found in the Zarxio labeling. The argument is that the absence of such data will hinder a biosimilar sponsors’ ability to use their analytical and clinical data in marketing and promoting the products.
Is this contrary to existing guidance? Technically no. Per a 2012 draft guidance document on scientific considerations in demonstrating biosimilarity, FDA said biosimilar labeling should include all the information necessary for a health professional to make prescribing decisions. This would include a “clear statement” advising that the product is approved as a biosimilar to a reference product, and whether the product has or has not been deemed interchangeable with the reference biologic. BUT, the labeling-related language was from the final version of the scientific considerations guidance (issued in late April 2015).
That lack of granularity is particularly irksome to biosimilar manufacturers since being able to discuss the data underlying approved biosimilars will be critical to building support for biosimialrs amongst doctors, patients, and (critically) payers. Can you say FDAMA 114?
Beyond marketing and formulary concerns, there are also questions over who bears responsibility for updating a biosimilar’s labeling to reflect post-marketing adverse events. And what about the fact that the Sandoz product is not (at least not yet) deemed interchangeable by the FDA?
A side-by-side assessment of biosimilars and their reference product is a logical and appropriate exercise. Will it be considered violative, off-label communications?
Should it be specifically called out in 21st Century Cures? Should it await PDUFA VI? Or will the agency revise it’s current position of it’s own accord. And what will the impact of this issue be on biosimilar nomenclature?
Inquiring minds want to know.Read More & Comment...
I am putting in a lot of miles on behalf of international regulatory fraternity.
Over the last few months I’ve visited Egypt, Indonesia, Vietnam, Taiwan, Mexico, and Brazil, where I’ve had the distinct privilege to meet with regulatory and healthcare officials. (And boy, are my arms tired.) Many things were discussed and shared, but the red thread was the urgency of quality.
I’ve learned many things and met many remarkable people. Perhaps the most important thing I’ve come to appreciate is that we need to stop talking about regulatory “harmonization” and focus our time and attention on regulatory “convergence.” Just as every nation has it’s own unique culture and cuisine, so too must it design it’s own regulatory philosophy and structure. It’s not about replicating the USFDA or the EMA – it’s about converging towards best practices.
Beware the danger of regulatory imperialism. Expecting other nations with less experience and resources to “harmonize” with the USFDA or the EMA isn’t the right approach. Rather we should seek regulatory convergence, because that gives us a pathway to improvement – with the first step being the identification of specific process asymmetries that can be addressed and corrected.
And at the top of the list is quality.
Without quality, safety and effectiveness are non-starters. Without quality, healthcare spending is not just wasteful – but harmful. Without quality it’s al about price without any consideration for value. Without quality, regulation is a sham.
In April I spent three fascinating days in Sharm El Sheikh, Egypt at the Second Arab Conference on Food & Drugs. It was all business – and I didn’t even mind not getting any time to enjoy the Red Sea beaches.
Delegates from the Levant to Morocco had a lot to say and share. The fundamental take-away was that the Arab world is serious about coordinating their efforts in healthcare in general and in regulatory affairs specifically. “Convergence” and “harmonization” were the two key words of the event.
(The Middle East/North Africa Region – MENA – consists of 22 nations – but just 2% of global pharmaceutical sales.)
I was honored to present a plenary address on “Advancing Medicines Quality via New Strategies in Bioequivalence Regulations, Pharmacovigilance Practices, and the Identification and Management of Substandard Pharmaceutical Events,” as well as chair the event’s panel on pharmacovigilance, sharing the panel with governmental thought leaders such as Dr. Amina Tebba (Morocco), Dr. Amr Saad (Egypt), Dr. Emad Munsour (Qatar), and leading global policy experts Dr. Hisham Aljadhey (King Saud University), and Michael Deats (WHO). I also participated on a panel discussing the urgency of IP, as well as another on biosimilars – specifically calling out the vexing debate over nomenclature, physician notification, and therapeutic substitution.
With healthcare policy (as with life in general) – wherever you go, there you are.
Not surprisingly, much of the conversation centered on controlling costs – specifically pharmaceutical costs, without (alas) the appropriate balance of time spent on the pennywise/pound foolish consequences of many of these policies. The IP panel tried to add balance to that debate by strongly presenting the facts on the value of innovation.
Dr. Rasha Ziada (Egyptian Ministry of Health) made the important point that if a pricing authority doesn’t take outcomes into consideration, it will lead to overall price distortions. Amen. And Dr. Ola Ghaleb (Ministry of Health, United Arab Emirates), spoke about the UAE’s strategy of performance-based risk-sharing arrangements – but also how politics can derail any decision-making process. Her honesty was refreshing. Net/Net -- Outcomes is now capitalized and bolded in the international lexicon of healthcare policy.
While many of the presenters discussed the value of sharing pharmaceutical economic data across borders, there was not an equal counterbalancing discussion of the value of sharing clinical data for approvals and outcomes-based decision-making processes. But there was certainly an effort (both on many of the panels as well as during the breaks and after hours) to stress the urgency of this agenda. The good news is that many, many speakers (sometimes in passing and other times passionately) made the point that it mustn’t just be about “getting the lowest price,” but also appropriately pricing the most clinically effective treatments. Bravo.
Many of the delegates said (from the floor as well as in conversation) that the conference was useful – but that action is required. In short – talk is cheap. My feeling (speaking privately with senior government officials from many of these nations) is that there is serious momentum for change (and even reinvention). But only time will tell.
As Deming said, “Change is not required. Survival is not mandatory.”
At the closing plenary session came “The Sharm El Sheikh Declaration.” The full document (in English translation) can be found here, but let me focus on the aspects that pertain to quality:
· Investing in training and qualifying inspectors of pharmaceutical factories and ensuring the application of good manufacturing practice (GMP).
· Strengthening drug post-marketing regulation through the establishment and activation of pharmacovigilance centers, while working on qualifying and training their workforce.
· Urging Arab countries to invest in training inspectors of pharmaceutical factories to raise the quality of the inspection process and ensuring the application of current good manufacturing practice (cGMP).
· Urging Arab countries to authorize performing bioequivalence studies and ensuring that they conform to the technical requirements of Good Clinical Practice (GCP) through regular inspection visits.
· Urging international drugs regulatory authorities in the Arab world to activate drug post-marketing monitoring programs through establishing pharmacovigilance centers and equip them with trained pharmacists and doctors.
(Pleased and proud to say that many of these recommendations came from the conference panel I chaired on pharmacovigilance.)
In May my regulatory travels took me to Asia. In Jakarta I met with senior hospitalists to discuss the impact of Indonesia’s new legislation (designed to provide universal access to healthcare) – and its impact on both the quality of medicines available and a physicians right to choose both therapy and brand. Senior healthcare leaders are concerned that insisting that the lowest priced product be used will result in suboptimal outcomes for those patients unable to access private healthcare. They recognize that a system that provides broader access to low quality care is not a victory. Bioequivalent does not equal identical. Biosimilar does not equal identical. The stakes are high.
Next up was the Javanese capital, of Yogyakarta for a symposium on pharmacovigilance held by Ahmad Dahlan University. The senior Ministry of Health official shared the fact that for a nation of 250+ million, there are but 10 people focused on pharmacovigilance. Talk about the Java Jive! She spoke of the need to develop better risk-based assessment protocols and better coordinate efforts with other nations in the region in order to share information on adverse events, bioequivalence, API and excipient sourcing. Quality is a team effort.
Meetings in Hanoi and Ho Chi Minh City focused on quality with a more specific focus on the need for more regular bioequivalence testing on patients under treatment (as opposed to healthy volunteers) in order to better understand not adverse events, but the uptick in Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. In Vietnam they are beginning to understand and appreciate that Small is the new Big. The need to focus on the individual patient rather than the general population and on long-term care rather than short-term cost.
The last stop on my Asian tour was Taipei, where I had the opportunity to speak to a colloquium of oncology physicians. Their fear and frustration was similarly directed towards a government healthcare program that mandates the use of lowest cost products. Nowhere does this cause greater angst and anger than with healthcare professionals treating patients with cancer. The unintended consequences caused by short-term, price-driven government policies on quality and clinical outcomes cannot be underestimated. Those on the front lines (physicians and pharmacists) understand this. And recognizing there is a problem is the first step towards solving it.
What have I learned? The only thing that’s grown more than my frequent flyer miles is my respect and admiration for those over-worked and under-appreciated civil servants toiling on the front lines of medicines regulation.
It’s a global fraternity of dedicated (and generally under-paid) healthcare and health policy professionals devoted to ensuring timely access to innovative medicines and quality generics drugs. It’s not easy and it’s not a job – it’s a personal public health mission.
There are many languages, priorities, pressures, and impediments (social, political, cultural) to consider, but one thing everyone agrees on is that quality counts. But what does “quality” mean – and does it mean the same thing from nation to nation and from product to product both innovator and generic? The good news is there’s general agreement that lower levels of quality for lower cost items aren’t acceptable. But the bad news is that there are gaps and asymmetries in how “quality” is both defined (through the licensing process) and maintained (via pharmacovigilance practices).
Can there be a floor and a ceiling for global drug safety and quality? Even as we move toward differential pricing, should we allow some countries to have lower standards than others “based on local situations?” Can one man’s ceiling be another man’s floor? Can a substandard medicine ever be considered “safe and effective?”
Aristotle said, “Quality is not an act, it is a habit.” Habits are learned and improve with iterative learning and experience. And nowhere is that more evidently manifested than through the many and variable methodologies for generic medicines licensing and pharmacovigilance practices. From paper-only certification of bioequivalence testing and questionable API and excipient sourcing, the safety, effectiveness, and quality of some products are, to be generous, questionable.
Is this the fault of regulators; of unscrupulous purveyors of knowingly substandard products; of shortsighted, overly aggressive pricing and reimbursement authorities? While there are many different and important avenues of investigation, the most urgent area of investigation should focus on the asymmetries in how quality is defined, measured, and maintained. That which gets measured, gets done.
National 21st century pharmacovigilance practices must also take into consideration the realities of funding, existing staff levels, training programs, and existing regulatory authority. Accessing increased regulatory budgets is problematic. Should licensing agencies consider user fees for post-market bioequivalence testing of critical dose drugs? That’s a contentious proposition– but agency funding is an often-overlooked 800-pound gorilla in the room and deserves to be seriously discussed and openly debated.
Another uneven issue is that of transparency. While regulatory standards are undeniably an issue of domestic sovereignty, shouldn’t there be transparency as to how any given nation defines quality? “Approved,” means one thing in the context of the MHRA, the USFDA, and Health Canada (to choose only a few “gold standard” examples), but how can we measure the regulatory competencies of other national systems? Is that the responsibility of the historically opaque WHO? What about the regional arbiters? Should there be “reference regulatory systems” as there are reference nations for pricing decisions? And how would this impact the concept of regulatory reciprocity?
In our globalized healthcare environment of SARS, Avian Flu, and Ebola, it’s important to remember that a rising tide floats all boats.
And so home again, home again, jiggity jig to an American healthcare system debating many of the same issues – bioequivalence, biosimilarity, interchangeability, physician notification, substandard pharmaceutical events, patient/physician/pharmacist education, the price/value equation, short-term savings vs. long-term patient outcomes.
It’s a small world after all.Read More & Comment...
Reporting from The Hill ...
Bipartisan House committee leaders on Thursday announced a $13 billion deal to pay for the cost of a measure to speed the approval of new medical cures.
The 21st Century Cures measure, aimed at streamlining the FDA’s approval process for new drugs, has received bipartisan support in the Energy and Commerce Committee, easily passing a subpanel last week on a voice vote.
But the major remaining question was how to pay for the bill’s cost, most of which comes from more than $10 billion over five years in new funds for the medical research at the National Institutes of Health. The bill also includes $550 million over five years for the FDA, a key point for Democrats, who pushed to have the funds added.
Committee leaders in both parties worked intensely over the past few days to come to an agreement.
The deal puts the bill on track to be a rare bipartisan achievement. After a markup Thursday morning, committee leaders hope to have a full House vote in June.
“The policies in this package are long overdue and will pave the way for a new generation of health care innovation,” the bipartisan committee leaders said in a statement. “Too many patients and families have been waiting too long for cures — this bill will make a difference
The offsets include selling 8 million barrels of oil each year for eight years from the Strategic Petroleum Reserve, which the Congressional Budget Office says will bring in $5.2 billion.
A second change modifies the timing of government payments to insurance companies under the Medicare Advantage program so that the government can keep interest earned on the funds rather than the insurer. This measure will bring in between $5 billion and 7 billion.
A $2.8 billion change reduces Medicaid payments for certain medical equipment. It does this by lowering Medicaid payments to match the lower rates that Medicare pays for the same equipment. Medicare currently pays less because it uses a competitive bidding process.
The bill would also make $200 million by limiting payments for x-rays on film, incentivizing the switch to digital imaging.
The markup had been scheduled for Wednesday morning, but it was delayed for 24 hours at the last minute after Democrats asked for more time to review the offsets and work through changes.
Top Democrats on the committee had only seen the full offset proposals this week.
Rep. Jan Schakowsky (D-Ill.) said Wednesday that the offsets had been “sprung” on Democrats.
A Democratic committee aide pointed out it would be more customary to work out offsets later in the process after the bill passed committee, but attributed the faster timeline to Republican leadership wanting the bill to be paid for early on.
The committee’s chairman, Fred Upton (R-Mich.), said Wednesday that leadership wants “us to get our ducks in line,” and that offsets had to be worked out so that the bill could be scored by the CBO.
In a positive signal from leadership, the bill was given the number H.R. 6. Bill numbers 1-10 are typically reserved for the Speaker.
Committee leaders sent proposal back and forth this week, winnowing down a list of possible offsets.
Upton had a final meeting with the other leaders on the bill, Reps. Joe Pitts (R-Pa.), Frank Pallone (D-N.J.), Gene Green (D-Texas) and Diana DeGette (D-Colo.) on Wednesday before the group broke to brief the members in their respective parties.
Upton said Wednesday evening that committee Democrats had met at 5:30 p.m. that afternoon to go over the deal.
“We haven't heard any blowback, so I'm sensing that what we discussed earlier is going to hold,” he said. “So we're there.”Read More & Comment...