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CVS’ ballyhoo that they “reduced the rate of drug spending” in 2015 is barely half the story. And as my grandmother used to say, “A half-truth is a whole lie.”
CVS, which manages drug benefit plans for more than 75 million Americans, kept costs down in 2015 by negotiating discounts from big manufacturers and carefully managing its list of covered drugs – and by denying patients the medicines prescribed by their physicians.
Yes, they decreased RX expenses but they haven’t any clue what happened to overall healthcare costs, out of pocket costs and, more importantly, patient outcomes.
In a nutshell, CVS removed some drugs from formularies and limited access to others – and asthmatics are in the emergency room. That’s not a public health victory. Read More & Comment...
At a crucial moment in American (indeed global) healthcare, he brings a vision for FDA as an innovation accelerator, steward of post-market safety, guarantor of quality, and first among equals when it comes to leading the agency’s intramural partnerships on a plethora of issues with its many constituencies. Perhaps most importantly, is Califf's role as agenda-setter and cheer leader at an agency comprised of highly educated and dedicated (and career) public servants.
The past is prologue. Read More & Comment...
Now policymakers want to make sure you don't have to be an ex-President to get the best treatment immediately:
Georgia Bill Inspired by Jimmy Carter's Cancer Treatment
Georgia lawmakers have approved a bill inspired by former President Jimmy Carter's cancer treatment.
The bill prevents insurance companies from limiting coverage of drugs for stage 4 cancer patients.
Carter, now 91, announced in August that he had been diagnosed with skin cancer that had spread to his brain and would begin receiving doses of Keytruda. The newly approved drug helps his immune system seek out cancer cells appearing in his body.
Carter said in December that a scan of his brain detected no sign of cancer cells. He has continued treatment.
Republican Rep. Mike Cheokas from Americus is the bill's sponsor. Cheokas said no one facing cancer that has spread should have medical treatment options limited by insurance providers.
The bill now goes to the state Senate for review.
In introducing the bill, Representative Cheokas said something that should be a campaign slogan nation-wide: "Cancer is a non-partisan issue. It affects young and old, black and white, rich or poor; It really doesn't matter."
Read More & Comment...
But the real heroes in the ‘battle’ to reduce what are always referred to as skyrocketing drug costs are people like Nicole who are denied access to new medicines in order to pad the profits of CVS and other PBMs:
Nichole, a 25-year-old living with Hepatitis C, was desperate when she reached out to WBZ-TV.
“A week ago, I didn’t feel any hope,” she told the I-Team.
She had been struggling with the disease since she was abducted four years ago. The fatigue and jaundice, plus the stigma made it hard to get on with her life.
Making matters worse, the man who victimized her had received a life-saving cure in prison.
Nichole was left only with multiple denial letters from her insurance company, Tufts Health Plan.
“Aside from the physical, emotionally, this has been horrible,” she told WBZ in January.
Nichole’s doctor prescribed it saying she was a perfect candidate. It would help rid her of the disease and move on. However, a full treatment of Harvoni is priced at a whopping $84,000. That’s $1,000 per pill. Tufts Health Plan denied Nichole coverage of the drug, saying she isn’t sick enough yet. “The insurance company wants me to be in Stage 3 liver scarring,” she said.
Let the record show that this denial comes from CVS, the hero of drug pricing critics. And the rationale for rationing Nicole is courtesy of our friends at the Institute for Clinical and Economic Review. These drug price watchdogs, as their acolytes in the media has hailed ICER, has recommended that HCV patients like Nicole be denied cures until there “is some evidence of liver fibrosis.” More on this media anointed (as well as health plan and Enron billionaire funded) arbiter of price and the value of a human life in a future post.
And don’t forget that CVS has an exclusive deal with Gliead to make it the only HCV drug on their formulary. But even then, you have to fail first or get liver damage to try another drug.
Nicole is one of the lucky ones. According to Camilla Graham, MD, assistant professor of medicine at Beth Israel Deaconess Medical Center in Boston. Every single Viekira Pak scrip she has written for her Medicaid patients has been denied. “Things aren't going so well, and Massachusetts, I will say, has the best access of any state. Our Medicaid doesn't have ridiculous restrictions,” she says. “I'm calling them restrictions, but it's really rationing. We're seeing rationing of care for hepatitis C like I've never seen in U.S. medicine.”
CVS’ chief medical officer, Troyen Brennan, said that without Sovaldi being introduced, the 11.8% growth might have been about 10%, and that this year’s spending growth would have remained at about 5%.
But wasn’t Solvadi going to increase premiums by 30 percent? Brennan co-authored a piece in JAMA in which he asserted. “ The simple math is that treatment of patients with HCV could add $200 to $300 per year to every insured American's health insurance premium for each of the next 5 years,"
That’s BS obviously. Even worse, it was BS used to justify rationing drugs and cutting exclusive deals with drug companies so that sick patients would have to beg for cure.
Meanwhile, the “fine-tuning” as Matt Herper happily describes is more like a blitzkrieg against access. As Adam Fein dryly notes:
Express Scripts has 66 products on its 2015 formulary exclusion list, compared with 48 in 2014. CVS Caremark’s 2015 list has 95 products, including 72 carryovers from the 2014 edition. Nostalgic readers will recall that CVS Caremark removed a mere 34 drugs from its 2012 standard national formulary. I guess there ain't no valley low enough, either.
Adam’s right. CVS and other PBMs haven’t reach their low point in limiting access, cutting deals and using ICER as a price fixing front in order to maximize the spread between the net cost of a drug (often up to 40 percent of average wholesale price) and how much they force patients to pay out of pocket for medicines that are right for them.
As Stacy Trooskin, MD, PhD, assistant professor in the division of infectious diseases and HIV medicine at Drexel University College of Medicine in Philadelphia points out: “I get a little bit concerned when we have exclusivity deals and none of these price cuts that the payer is receiving from the pharmaceutical company translate to ease of access.”
The decline in drug costs is a result of the increased success of PBMs extracting rebates and denying access. A Credit Suisse analyst report found that: “For 2014, our 20 company universe has shown net US drug sales of $202bn and reported total rebates of $98bn. We conclude that in 2014 US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures. “
Which means that 2015 was a great year for PBMs because it was worse for patients.
Read More & Comment...
The most important outcomes are steps that are intended to improve FDA’s ability to recruit, hire and retain scientific staff, measures to improve the agency’s financial transparency and accountability, and extensions of ongoing efforts to integrate patient perspectives and real-world data into regulatory decision making.
Completion of the goals letter, expected in March, and review by HHS and the White House over the summer, will mark the end of the first phase of the PDUFA reauthorization process. But it only will launch the start of the much more arduous portion of the PDUFA reauthorization journey: congressional approval.
I. Fixing HR
FDA’s ability to meet user fee review goals, and to go beyond them by implementing new regulatory ideas and proactively supporting product development, depends almost entirely on its ability to recruit, retain and develop talented and dedicated staff.
At the start of PDUFA VI negotiations, PhRMA and BIO told FDA that industry would not support increases in user fees to hire new staff unless CDER demonstrated that it had put procedures in place that would fill staffing holes and provide confidence it could hire to fill new positions funded by PDUFA VI. According to industry negotiators, CDER and FDA have met the challenge, in part by taking some steps that are common in the private sector, such as hiring external head hunters.
Unlike previous user fee agreements, which paid for FTEs even if they were never hired, the agency will only receive the additional money if it meets recruitment and retention goals. FDA has also agreed to hire an external organization to assess and continuously evaluate its hiring and retention efforts.
Other nuts-and-bolts activities covered in PDUFA VI include improving the reliability of the electronic filing process for new drug applications, steps to improve the management of meetings between FDA and sponsors, and revamping a formula that is used to increase user fee payments based on estimated workload.
II. Breakthroughs and Biomarkers
Some of the new hires will work on improving FDA’s review of products that combine drugs and devices, and on the breakthrough therapies program. The breakthrough process is resource-intensive, and the largest allocation of new staff in PDUFA VI, about 60 employees, will be dedicated to breakthrough reviews. PDUFA VI will also include additional money and mandates for FDA to review drug development tools, including surrogate endpoints, biomarkers and patient-reported outcomes (PROs).
Alas. industry dropped attempts to establish review time goals for biomarker qualification.
Advancing FDA’s patient-focused drug development (PFDD) initiative is another priority for patient groups as well as for industry and FDA. FDA has already started expanding PFDD by encouraging patient groups to hold their own meetings modeled on meetings the agency has held. PDUFA VI will include a series of guidance documents that are intended to lead to PFDD version 2.0, which could include establishing standards for conducting and analyzing patient-preference research, and taking steps to formally integrate patient preferences into regulatory decisions.
FDA created structured benefit-risk frameworks during PDUFA V, and will expand their use in PDUFA VI.
Advancing the use of real-world evidence to make regulatory decisions will be another major emphasis of PDUFA VI. This will include enhancing the Sentinel Initiative, a system that allows investigators to monitor and query electronic medical records, health claims databases and other sources. Projects under consideration for Sentinel include monitoring the safety of biosimilars, and broadening its focus from safety to efficacy.
Biopharmaceutical companies are looking to PDUFA VI to open legal avenues to communicating with payers and possibly other parties about real-world data on off-label uses of approved drugs.
Finalization of the draft PDUFA VI goals letter will set in motion a series of reviews by HHS and the White House Office of Management and Budget that are slated to be completed by September. Following publication of the draft agreement in September, and a final public meeting in October or November, the deal should be formally submitted to Congress in mid-January.
PDUFA VI AT A GLANCE
* Improve FDA recruitment, hiring, retention: Implement HR improvements, hire outside HR contractors, contract for external analysis and monitoring of progress
* Funding for about 200 additional full-time employees (FTEs): Funding contingent on FDA meeting recruitment, retention goals
* Increased funding for breakthrough reviews: Largest portion of new FTEs
* Modification of the “workload adjustor” formula used to increase user fee payments based on anticipated submissions: Annual user fee increases expected to be smaller; FDA to gain more predictable funding
* Patient-focused drug development 2.0: Issue a series of new guidance documents on patient-focused drug development
* Research on the integration of real-world evidence into product reviews: Expand Sentinel Initiative, a system for postmarket monitoring and querying of electronic health records, insurance claims and other records to track medical product safety; Implement other efforts to use real-world evidence to study and communicate about safety and efficacy
* Increased funding for review of drug development tools: Add resources to qualify surrogate endpoints, biomarkers, patient-reported outcomes; Expand use of benefit-risk framework to guide drug development activities; Enhance FDA capacity to analyze innovative clinical trial designs
* Increased transparency regarding spending PDUFA funds
* Information technology improvements: Increase reliability of the electronic submissions system, upgrade CDER's IT system Read More & Comment...
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.” Read More & Comment...
Take this story from Minneapolis.
A major company has rolled back the price of a potentially life-saving prescription drug after a KARE 11 News investigation.
But the decision has some people asking how often we’re being overcharged on other medicines.
It started with Curt Burshem.
Back in November he told us CVS Caremark had jacked up the price for a prescription drug a family member needed for a kidney disorder.
Curt Burshem discovered that CVS was overcharging him on prescription drugs.
"When I see a company doing this crap, it makes me insane,” he said.
But, now, CVS has reversed the price high.
"Justice had been served,” Curt told us.
When Curt originally went to the CVS pharmacy in Maple Grove last Spring, the initial 30-day supply cost about $.87 per pill.
But when he followed his insurance company’s advice and ordered a 90-day supply through the mail, CVS Caremark increased the price to more than $6 a pill.
After KARE 11 called CVS they rolled the price back and gave Curt a refund.
Which raises the question: If transparency proponents were intellectually honest (some are, most are not) they would demand the same openness from every health care institution that shapes access to and the price of medicines.
Will PBMs and insurers reveal how they move from drugs that they acquire at 40-60 percent below pharmacy retail prices to charging consumers 30 percent of that retail price?
Will PBMs and insurers reveal how and why they decide when their customers are forced to fail first on medicines?
We need to know. They claim drug costs are climbing at an unsustainable rate. That doesn’t square with data since 2000, spending on drugs has remained at 9-10 percent or HHS projections that overall drugs will remain at about 9 percent of total health spending through 2030. So why are copays and co-insurance rates increasing??
Will hospitals reveal how they go from drugs acquired at the same rate to charging up to 700 percent of retail prices? And while they are at it, will they explain why charges for hospital care increased faster than drugs, even as the use of these new medicines reduce hospital costs? Why has hospital spending increased 6 times faster than drug spending between 2010-2013?
If I am a pharmaceutical company, I’d be for transparency for everyone. I’d show them mine, if they showed theirs. Let’s have the Full Monty for all. Read More & Comment...
In a cramped Mumbai paediatric ward, third-year pharmacology student Nitin Shinde opens the boy's file and notes the vaccine, his age and the doctor's diagnosis of a skin infection. That information is later logged into a computer programme linked to a national database, part of India's fledgling efforts to track, analyse and ultimately warn patients about unknown side effects of drugs on the market.
India's six-year-old pharmacovigilance programme, which collects and submits suspected adverse drug reactions to a World Health Organisation (WHO) database, is key to improving drug safety in a country where medicine consumption is high, experts say.
But insufficient staff and equipment, and a lack of awareness among medical professionals mean many potentially dangerous drug reactions go unrecorded, hospital personnel across India told Reuters.
Gaps in the system mean the government has less data to determine whether drugs might have harmful side effects. Also, relatively little information flows from one of the world's largest pharmaceutical markets to the WHO database of over 12 million suspected adverse drug reactions.
"In a country of 1 billion people consuming so much medicine, obviously safety is a concern," said G. Parthasarathi, dean of the pharmacy school at JSS University in Mysore, adding the pharmacovigilance programme is still gaining traction. "We've made a good start," he said.
Last year, India contributed 2 percent of the 2.1 million suspected reactions added to VigiBase, the WHO's global database. China, with a comparable population, contributed 8 percent.
Indian health officials say the monitoring programme is a "high priority" and a $14.5 million annual budget is sufficient.
"We are going to develop a better pharmacovigilance system in India in due course," said G.N. Singh, India's drug controller. "Patient health will be assured."
Regarding doctors' lack of engagement, "the culture of reporting is improving," said V. Kalaiselvan, principal scientific officer at the Indian Pharmacopoeia Commission.
The full Reuters article can be found here.
Read More & Comment...
Much of what passes for journalism or commentary about the biotechnology/pharmaceutical industry is click driven hate mongering. Want to write about drug companies. Start with this theme: Everything drug companies do is disgusting. Nothing they do is beyond reproach. Use h one example of unseemly behavior and claim every company does the same thing. Add some anger and sarcasm.
Pharma sucks. Ha-ha.
Press send or post.
Here’s some recent examples in order (mostly) of idiotic magnitude:
Here’s what White House Chief of Staff Denis McDonough said in the wake of a Super Bowl commercial to raise awareness of opioid-induced constipation run two companies marketing a drug to treat it: “Next year, how about fewer ads that fuel opioid addiction and more on access to treatment.” commercialized and misused pharmaceutical knowledge,” he told a United Nations agency.
Apparently McDonough never got the memo that people – including millions of cancer patients and individuals with digestive tract paralysis who safely use opioid based drugs to control searing pain – should have the same right to poop as White House staffers.
Bill Maher tweeted (and this is evidence of why humor should be left to humorists) “Was that really an ad for junkies who can't shit? America, I luv ya but I just can't keep up.”
In between the harsh sarcasm of the White House and Maher’s tweet is the much needed gap created by Samantha Allen of the Daily Beast:
Martin Shkreli Is Just One of Many Pharma A-Holes
Nancy Retzlaff is not Martin Shkreli. She won’t inspire hundreds of news articles nor will she become the subject of any Internet memes. She won’t threaten Ghostface Killah and it seems unlikely that she will ever flirt with a minor on a YouTube livestream.
But the chief commercial officer for Turing Pharma is just as responsible for keeping the price of the life-saving drug Daraprim 5,000 percent higher than it used to be. And as long as the public eye is still trained on the Shkreli sideshow, she’ll get away with it.
….There are more Martin Shkrelis out there, and not all of them are acting like assholes on Twitter. And if the Shkreli Show overshadows the people who still need easy access to a once-affordable treatment, everyone loses. The Pharma Bro started out as a poster child for a pressing problem. He may end up being a red herring.”
Samantha Allen seems eminently qualified to cover the relationship between being an asshole and drug pricing. She has a PhD in Ph.D. in Women’s, Gender, and Sexuality Studies from Emory University. She In 2013, she received the John Money Fellowship for Scholars of Sexology from the Kinsey Institute. She used the money to “research a wide range of media (books, photos, videos, graphic art, tabloids, etc.) on several different sexual fetishes (shoe, foot, nylon, pantyhose, breast, spanking, hair, etc.) dating from across the 20th and 21st centuries.”
Is this a great country or what?
But Dr. Allen is also an asshole expert because she is a misandrist. In case you are wondering, that means she hates men:
“i hate men because it’s not my job to fix masculinity; it’s my job to heal from it and to be together with my sisters as we try to make it through a hostile world. and yet i am expected to patiently educate men on how not to be an asshole. here’s my only tip: stop spending so much time around men. they’re assholes.”
Finally, here’s someone attacking drug companies for changing all human and cultural concepts in the world so widely that treatment is completely considered as a business in the world today..We should revive our traditional medicine which is in harmony with our culture and is naturally cheaper and more useful.”
That last statement is from former Iranian President Mahmoud Ahmadinejad who blamed “Zionist medicine” for polluting our planet with profitable but useless medicines.
You knew it had to come down to the Jews controlling Big Pharma this:
“Martin Shkreli (pictured) is a Jewish businessman (he has relatives living in Albania, and is often referred to as an Albanian). Though his Wikipedia page says he is Albanian and Croatian, he was born and raised in Brooklyn, went to Baruch College, worked for uber-Jewish hedge fund manager Jim Cramer in his teens — and had his own hedge fund by the time he was 21.
When the Jews want to profit more from selling a drug needed to treat sick people, who otherwise would die, they don’t just raise the price by a factor of five or ten. They send someone to raise it by a factor of fifty, wait for the reaction to hit the press, then they pretend to back down… yessir, all the way down to where they had planned to put the price from the beginning.
… This is a Jewish business strategy. Whenever they want to do something that they know will antagonize the public, they have one of their own, or someone under their control, do something even worse, and then they pretend to “correct” their own agent by telling him to stop doing it, and start doing something that isn’t quite so bad instead.”
Or as Dr. Allen put it:
Martin Shkreli became the public face of price gouging because he was so transparent. But Retzlaff’s cool, calm, and collected attempt to spin the same exorbitant price increase for an HIV drug as a net good is arguably more dangerous because it is less obvious.”
There’s no underlying similarity binding these anti-pharma and anti-Semitic rants except varying degrees of paranoia and this observation by George Orwell: “If thought corrupts language, language can also corrupt thought.”
Read More & Comment...
From the very beginning of the hearing, it was clear the expert members of the committee didn’t understand what biosimilars really are, nor the pathway the agency uses to review them.
And yet, at the end of a long day they were asked to vote on this question:
Does the Committee agree that based on the totality of the evidence, CT-P13 should receive licensure as a biosimilar product to US-licensed Remicade for each of the indications for which US-licensed Remicade is currently licensed and CT-P13 is eligible for licensure (RA, AS, PsA, PsO, adult CD, pediatric CD, adult UC)?
Despite open public comment from patients and physicans concerned about extrapolation issues, the vote was 21-3 in the affirmative. It was the vote the FDA wanted. And they got it.
Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified as potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
What does the FDA know that our European and Canadian regulatory cousins do not?
There was also much chatter amongst the panel members about this vote helping to lower prices. Maybe so. Maybe not. Either way it’s not an appropriate discussion for an FDA panel.
Read More & Comment...
The event’s lead-off hitter is Dr. Doug Throckmorton, CDER’s Deputy Director for Regulatory Programs and the FDA’s point-man for opioids. His talk, “The Future of Abuse-Deterrent Formulations,” is a timely must-hear presentation.
Read More & Comment...
Does Califf’s Opioid Announcement Go Far Enough?
Sens. Joe Manchin (D-W.Va) and Edward Markey (D-Mass.) will maintain their holds on the nomination of Robert Califf for the top job at the FDA, despite the agency’s announcement Thursday that it would overhaul its opioid policies.
Specifically, the FDA said it would reexamine its approval, REMS and postmarket policies for opioids in response to a growing abuse epidemic and calls to action from lawmakers.
The senators — along with Sen. Bernie Sanders (I-Vt.) — in January placed holds on Califf’s nomination, with all three citing the FDA’s handling of approving prescription opioids.
A spokeswoman for Manchin tells DID that the senator’s plans have not changed, and he still plans to filibuster and hold Califf’s nomination. Manchin said the FDA’s announcement that it would re-evaluate its risk-benefit framework for the drugs will only “slightly improve” the agency’s response to the opioid epidemic, and that “sweeping changes” are still necessary.
Markey said in a statement that the FDA’s actions are “some important steps” but “fall short of what is needed.”
Andrew Kolodny, director of Physicians for Responsible Opioid Prescribing and the chief medical officer of Phoenix House, tells DID that many of the FDA’s “speaking points” are “meaningless.”
He criticized the agency’s announcement that it would convene an advisory panel before approving any new opioids that lack abuse-deterrent properties, asserting that these meetings should be held for all approvals regarding opioids.
Senator Markey also made that point: “By refusing to convene advisory committees to inform all of its opioid approval decisions, the FDA continues to ignore outside experts who could help stem the tide of tragic deaths and overdoses plaguing the country,” Markey said in a statement. He also said he would continue to hold off on Califf’s nomination “[u]ntil the FDA commits to convene advisory committees of outside experts for all its opioid approval decisions.
Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, tells DID that he thinks the FDA’s approach could make a difference, saying it will make the approval process “more complete.” “I think there will be a higher evidentiary standard on the one hand, but on the other hand there will be a clearly explained pathway as to how to achieve it. They're taking ambiguity out of the process.”
Pitts added that the approach is going to provide guidance on how to develop abuse-deterrent opioids and how to use real-world data to impact post-approval labeling. Read More & Comment...
Celltrion conducted clinical studies of CT-P13 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and is seeking extrapolation of CT-P13 across all seven of Remicade's approved indications including Crohn's disease, pediatric Crohn's disease, ulcerative colitis (UC), pediatric UC, psoriatic arthritis and plaque psoriasis.
In the briefing documents, FDA reviewers said the preclinical, clinical and manufacturing data submitted by Celltrion suggest that it is "highly similar" to Remicade. Agency officials noted that while there were differences in the binding of the Fc regions between Remicade and CT-P13, "it is reasonable to extrapolate conclusions regarding the similar efficacy and safety of CT-P13 and U.S.-licensed Remicade to IBD."
In brief, the FDA recommends approval for all indications mostly based on analytical studies along with some clinical (primarily for RA and AS data). Emphasis on analytics is not surprising based on the FDA biosimilar pathway – but what is interesting (and disturbing) is the absence of available real world data. More on this important patient safety issue shortly.
Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified as potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
AdComm members will be asked to discuss the similarity of CT-P13 to Remicade, whether there are clinically meaningful differences between the two mAbs, and whether there are sufficient data to support extrapolation to the approved indications beyond those studied in clinical trials. The panel will vote on whether CT-P13 should be approved as a biosimilar of Remicade for each of the seven indications.
Interestingly, the FDA has will not ask the panel to discuss any of the comparative real world data available that speaks to relevant clinical outcomes. This is particularly disturbing since (on page 11 of the briefing package) the agency FDA made statements on switching (per RA and AS) that would support the safety of a one-time switch from innovator to biosimilar. This is particularly important since Celltrion is NOT seeking interchangeability.
Should “defacto interchangeability” be an acceptable regulatory pathway?
Specifically absent from the FDA AdComm package is data from a study, from Mercy University Hospital, University College Cork, Centre for Gastroenterology, Mercy University Hospital, Cork, Ireland, which studied the clinical impact of both the innovator product (Remicade) and CT-P13, the Celltrion biosimilar. The findings are important. Specifically, the rates of surgery of the groups were significantly different.
80% of biosimilar patients required hospital readmission versus 5% of the Remicade) group. (p=0.00004). 60% of patients in the biosimilar group needed steroid augmentation of standard steroid tapering protocol with 50% requiring multiple increases in steroid dose versus 8% of those patients on Remicaide (p-value = 0.0007). Over the course of 8 weeks, 93% of patients in the biosimilar group had an increase in CRP with 7% remaining unchanged whereas 100% of patients in the Remicade group had a decrease in CRP (p=<0.001).
The study’s conclusion is not ambiguous, “Our results suggest that biosimilars may not be as efficacious as the reference medicine. The results found reflect the ECCO statement position that the use of most biosimilars in IBD will require testing in this particular patient population and cannot be extrapolated from other disease populations."
The complete poster can be found here.
An American College of Rheumatology abstract of CT-P13 data shows important differences between adverse events in patients with rheumatoid arthritis and those with ankylosing spondylitis depending on whether or not they were switched.
The ACR abstract can be found here.
The efficacy data was good. But the safety data is concerning. But the FDA AdComm won’t be discussing this study either.
Biosimilarity and measurement of efficacy is only one dimension. Attention must be paid to effectiveness relative to real-world patient outcomes data. Regulatory sins of omission are dangerous when it comes to the public health. Read More & Comment...
The FDA has announced a far-reaching action plan to reassess the agency’s approach to opioid medications. The plan will focus on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief.
Importantly, the FDA’s strategies and tactics are not adverse to the well-being of pain patients and avoid measures (such as mandatory advisory committees for abuse deterrent formulations) that would have the negative consequence of chilling investment in the science of abuse deterrence.
The FDA will:
• Re-examine the risk-benefit paradigm for opioids and ensure that the agency considers their wider public health effects;
• Convene an expert advisory committee before approving any new drug application for an opioid that does not have abuse-deterrent properties;
• Assemble and consult with the Pediatric Advisory Committee regarding a framework for pediatric opioid labeling before any new labeling is approved;
• Develop changes to immediate-release opioid labeling, including additional warnings and safety information that incorporate elements similar to the extended-release/long-acting (ER/LA) opioid analgesics labeling that is currently required;
• Update Risk Evaluation and Mitigation Strategy requirements for opioids after considering advisory committee recommendations and review of existing requirements;
• Expand access to, and encourage the development of, abuse-deterrent formulations of opioid products;
• Improve access to naloxone and medication-assisted treatment options for patients with opioid use disorders; and
• Support better pain management options, including alternative treatments.
As one of the cornerstones of this plan, the FDA will seek guidance from outside experts in the fields of pain management and drug abuse. For example, the FDA has already asked the National Academy of Medicine to help develop a framework for opioid review, approval and monitoring that balances individual need for pain control with considerations of the broader public health consequences of opioid misuse and abuse.
“We are determined to help defeat this epidemic through a science-based and continuously evolving approach,” said
Per Rob Califf, the FDA’s Deputy Commissioner for Medical Products and Tobacco “This plan contains real measures this agency can take to make a difference in the lives of so many people who are struggling under the weight of this terrible crisis.”
In addition, the FDA will convene independent advisory committees made up of physicians and other experts when considering for approval any new opioid drugs that do not contain abuse-deterrent properties. The FDA will also convene a meeting of its standing Pediatric Advisory Committee to make recommendations regarding a framework for pediatric opioid labeling and use of opioid pain medications in the pediatric population.
The FDA is also strengthening the requirements for drug companies to generate postmarket data on the long-term impact of using ER/LA opioids. The agency expects this to result in the most comprehensive data ever collected in the field of pain medicine and treatments for opioid use disorder. The data will further the understanding of the known serious risks of opioid misuse, abuse, overdose and death.
The FDA’s full announcement can be found here.Read More & Comment...
On February 9th, the FDA’s Arthritis Advisory Committee will discuss biologics license application (BLA) 125544, for CT-P13, a proposed biosimilar to Janssen Biotech Inc.'s REMICADE (infliximab), submitted by Celltrion, Inc.
If the Adcomm gives a thumbs up and the agency approves the product, this will be the second biosimilar approved in the U.S., but the very first monoclonal antibody, a much more complex molecule than filgrastim.
Apart from the product issues, there are many important policy issues that should be discussed. For example:
Labeling, naming, coding, substitution, non-medical switching and interchangeability are all-important policy issues that FDA has the authority to impact and are appropriate to raise at a high level AdComm.
While extrapolation was allowed for filgrastim, the questions of extrapolation for this product are not as simple or straight forward for the following reasons:
Complexity and Stability
Filgrastim is generally not used as a long-term product for a life-long, chronic disease like infliximab and is much less complex than infliximab, which is nearly eight times larger. Monoclonal antibodies are used in patients with moderate to severe diseases like Crohn’s or ulcerative colitis and disease stability is critical. With biosimilar entry the risk of switching the patient to a new, similar product must be carefully considered due to the complexity of the product and disease state.
Regulatory Authorities Split
Because biosimilars are not identical copies of their reference products, even slight differences in structure can affect the biosimilar’s mechanism of action. Without clinical data in each therapeutic area, it may be challenging to understand the impact of these differences on clinical outcomes. Infliximab is particularly relevant to the overall conversation regarding indication extrapolation because structural differences have been identified which are thought to be potentially related to the treatment of inflammatory bowel diseases. The EMA has granted the product full extrapolation including inflammatory bowel diseases, while Health Canada did not, citing uncertainty regarding the clinical impact of observed structural differences.
Biosimilar sponsors compare the structure and function of their products to the reference product using a range of laboratory (i.e., analytical tests) tests. Because of the complexity and uncertainty with regard to monoclonal antibodies, we can’t always tell which product attributes (or parts of the structure) will be relevant to ultimate clinical outcome and which won’t be. This is why it’s critical that FDA take a conservative approach and ensure that the biosimilar and reference product are as highly similar as possible, across a wide variety of structural and functional attributes.
Studies Suggest Different Response in Different Disease States
An American College of Rheumatology abstract of infliximab biosimilar data shows difference between adverse events in patients with rheumatoid arthritis (RA) and those with Ankylosing Spondylitis (AS) depending on whether or not they were switched with a 22.5% difference in AS patients that were switched:
* Ankylosing Spondylitis (AS) TEAEs - 48.9% on biosimilar; 71.4% switched from innovator to biosimilar
* Rheumatoid Arthritis (RA) TEAEs – 53.5% on biosimilar; 53.8% switched from innovator to biosimilar.
Regulatory authorities recognize the importance of robust post-marketing safety monitoring for all drugs including biosimilars. What make biosimilars different from other drugs however is that unlike generic small molecule medicines where safety can be assumed to be identical as its branded counterpart, a biosimilar is not identical to its reference drug. Another defining difference with biosimilars is that all biologic medicines may trigger the human immune system to react in undesirable ways such as rendering the medicine ineffective. Small difference between products may result in different effects on the body’s immune system.
* Post-marketing safety monitoring is heavily dependent upon voluntary reporting of adverse events by health care professionals and patients. Unfortunately, this system does not have the capability to effectively monitor and accurately identify adverse events as a result of triggering the body’s immune system. It is unclear how regulators can or will implement robust ways to compare the safety of a biosimilar to its reference product once approved.
It may be February in Maryland – but the heat is on the FDA.Read More & Comment...
BIO released a set of voluntary principles that include a set of commitments by the trade group and its member companies to support "comprehensive and sustainable solutions to improve patient access to and affordability of innovative medicines." The principles include a commitment to work with payers, healthcare providers and policy makers to maximize patient benefit and drive "smarter" healthcare spending via "value-based and outcomes-based contracting arrangements, patient adherence and education programs, alternative financing and payment mechanisms, or other similar options."
Thee BIO PRINCIPLES ON THE VALUE OF BIOPHARMACEUTICALS begins as follows:
BIO member companies are committed to investing in, developing, and delivering innovative biopharmaceuticals that are transforming how we treat and cure patients with once-devastating diseases – giving them hope, extending survival, and saving millions of lives. The value that these innovative medicines offer to patients and their caregivers, the healthcare system, and society at large is truly a game-changer. The critical issue is how best to ensure that these medicines are accessible to patients in need, while continuing to foster the risk-taking required to sustain the promise of future treatments and cures. This issue is the subject of vigorous public policy debate, and we welcome it.
Per a report in BioCentury, Ron Cohen, president and CEO of Acorda Therapeutics Inc. and chairman of BIO, the trade group is putting the final touches on a media and lobbying campaign emphasizing the value of biopharmaceuticals and the high costs of other healthcare products and services. BIO's new principles also include a commitment to work with policy makers to "remove legal barriers that currently limit the ability to engage in value-based contracting and communications."
Stakeholders also told BioCentury that regulatory barriers to outcomes-based pricing contracts include FDA's prohibition on discussion of off-label uses of drugs and agency regulations that prevent companies from working with payers prior to approval to develop creative payment strategies. The FDA has listed these issues as key topics for the agency to address in its 2016 guidance agenda process.Read More & Comment...
Well sort of. As Adam Fein has noted, most generic drug price increases are a response to shortages, of which we have way too many. In most cases, the price increases can be blamed on drug shortages. "For example, the NADAC per unit for doxycycline hyclate (100 mg tab) increased from 5.6 cents to $3.65 (+6,351%). The increase is most likely due to a nationwide shortage. I presume there’s also an active gray market, as in generic injectables. For context, see Drug Shortages and Gray Market Profiteering."
And the retail price, once again, is not the real price. Again, Adam (drug)channels Mr. Spock in his logical analysis of the gap between retail and acquisition cost.
Adam's columns on pricing are more educational and authoratative than the turgid reports from some members of Congress.
Read More & Comment...
Two new lows were hit by Robert Langreth (with Rebecca Spalding) at Bloomberg and USA Today's Jane O’Donnell.
Langreth and Spalding wrote a predictably predictable article on the eve of Martin Shkreli’s no show congressional flogging. Predictable and derivative since it recycled the same stuff written by other low achieving reporters. The headline says it all: Shkreli Was Right: Everyone's Hiking Drug Prices.
So I will respond by recycling a previous blog on a ‘me-too’ pricing article in noting that Langreth fails to put drug price increases (net price or otherwise) into perspective. Langreth states that U.S. prescription-drug spending rose 12.2% in 2014, accelerating from 2.4% growth in 2013. But “price increases for protected brands increased spending by $26.3 billion, contributing 8.2% to total market growth on an invoice price basis; estimated net price growth was substantially lower as rising off-invoice discounts and rebates offset incremental price growth and reduced net price contribution to growth to 3.1%.”
That’s an increase in spending of about $7.1 billion. Total US health care spending increased by $100 billion from 2013-2014. So brand drugs were 7 percent of that amount.
O’ Donnell takes reporting on drug prices to a new low in "Patient groups funded by drugmakers are largely mum on high drug prices" She accuses patient groups that receive support from biotech firms from blocking efforts to impose price controls. The headline is the tipoff. To be more precise, she let’s Zeke Emanuel do the smearing. If you want a job done well, hire a pro:
"It is worrisome because it is a conflict of interest even if you can’t prove it changes their position," says Ezekiel Emanuel, an oncologist and professor who chairs the University of Pennsylvania's department of medical ethics and health policy. "The patient voice carries a disproportionate amount of weight."
So if someone alleges it changes your position, that’s a conflict of interest.
By that standard, the patient groups she cites as conflict free should also be suspected of conflict. More specifically, the Patient Voice Institute works with the Leapfrog Group which also gets money from large employers, health purchasing groups and AARP. All three are quoted in the article. But applying Zeke’s conflict benchmark, the fact that I can’t prove any connection means it is a conflict.
The j’accuse of getting funding from corporations is a diversion. O’Donnell, like many of her colleagues fail to look at the cost of new drugs relative to what insurance companies spend. It’s about 3 percent. And that spending makes treating illness less expensive by reducing hospitalization, saves lives and improves quality of life.
The question O’Donnell ignores is the one the Leukemia and Lymphoma Society answered about a year ago: How much would it really cost to pay for the drugs insurers scream are too expensive?
They commissioned a Milliman study and found that it would cost on average about 50 cents per patient per month. If drugs were driving up overall costs (as opposed to reducing them, which they do) why such a small increase to make people whole?
O’Donnell had the opportunity and column space to look at this issue. Instead she went down a darker, more deceptive road. What a shame. Then again, it's not surprising. Read More & Comment...
Mark Baum’s self-serving op-ed in the Wall Street Journal (New Prescription for Lower Drug Prices) that compounded-drug makers can bring inexpensive, off-patent medicines to market, “if the FDA will let them” omits a key issue in the debate – public safety.
Just last week, two Alabama pharmacists agreed to plead guilty to criminal charges in connection with the 2011 deaths of nine Birmingham-area patients who allegedly received a contaminated compounded drug.
According to federal prosecutors, the drugs were contaminated from being prepared, packed or held in unsanitary conditions. The Centers for Disease Control and Prevention found the same bacteria on a water faucet in an open container of amino acid powder, and on the surface of mixing equipment that had been used to make the drug, according to federal prosecutors.
Also last week, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said she has ruled out the use of compounding to combat spikes in generic drug prices.
Woodcock told the U.S. Senate Health, Education, Labor and Pensions (HELP) Committee that "there are very great risks" from FDA allowing mass production of compounded drugs to reduce the cost of a generic drug. Woodcock said that while recent legislation gives FDA additional power to enforce quality standards on pharmacies that compound sterile injectable drugs, FDA has limited oversight authority over compounding of tablets and pills. She said FDA has recently withdrawn compounded vitamin and hormone products after pharmacies distributed potentially fatal super-potent formulations.
Despite Mr. Baum’s rosy commercial projections, compounded drugs may be sub- or super potent, contaminated, or otherwise adulterated. Additional health risks include the possibility that patients will use ineffective compounded drugs instead of FDA-approved drugs that have been shown to be safe and effective.
His company, Imprimis, has had challenges with its compounding facilities in New Jersey and Southern California, both of which have been issued letters from the FDA citing Common Good Manufacturing Practices (CGMP) violations that could call into question the safety and effectiveness of the drugs compounded there.
Putting price before patient safety is bad medicine and worse policyRead More & Comment...
Sleeping with the Enemy? Hardly. Eli Lilly & Co. has announced an important collaboration with an unlikely bedfellow – their Hoosier neighbor, Anthem. The goal is to help develop common ground on policy solutions related to cost and value. Finally – two important players understand that they are, in fact, on the same team.
More information can be found here.Read More & Comment...