New FDA Commisioner: Change Agent, not Bomb Thrower

12/15/2016 08:21 AM | Peter Pitts

From the pages of the Washington Examiner ...

Potential FDA chiefs eye faster drug approvals

Donald Trump's potential choices to lead the Food and Drug Administration have called for the agency to ramp up approval of new products, though in drastically different ways.

Two people have been floated as being under consideration to lead the agency: agency veteran and physician Scott Gottlieb and libertarian and investment firm director Jim O'Neill.

Both candidates reflect a desire by President-elect Trump to speed up approval of new products, albeit through different approaches. Trump didn't talk a lot about the FDA during the campaign, but he has said that the agency needs to cut red tape to get new products approved.

O'Neill is the managing director at the investment firm Mithril Capital, which was co-founded by Trump donor and Silicon Valley billionaire Peter Thiel. O'Neill also served as the deputy administrator in the Department of Health and Human Services during President George W. Bush's administration.

He previously has called on the FDA to approve drugs based solely on safety and not on effectiveness, a radical departure from the current approach.
The agency currently approves drugs based on whether they are safe and effective. However, it threads a fine line at times, balancing the risk of a drug versus the expected benefit, especially if it is a new or experimental treatment.

The agency this year approved an experimental therapy called Sarepta for the rare and deadly disorder Duchenne Muscular Dystrophy, but came under fire from consumer advocacy groups who say the agency should have rejected it because of serious safety concerns.

Gottlieb has called for a different regulatory approach at the agency, but hasn't gone to the same extremes as O'Neill.

In July, he advocated for clinical trials for drugs that treat rare diseases. He pointed to the 21st Century Cures Act, which Obama signed into law on Tuesday and would enable the agency to approve drugs using a different clinical endpoint called a surrogate measure.

"These are interim endpoints that can be used to more quickly gauge a medicine's benefit, such as measuring its ability to shrink a patient's liver rather than having to wait for kids to accrue enough disability to see if a drug can help them walk or breathe better," he wrote in the Chicago Tribune.
He also said the law nudges the FDA to make wider use of "adaptive" trials that test a drug on a smaller group of patients.

An agency veteran who worked with Gottlieb said that having support from the agency's career staff is vitally important to getting goals accomplished.
"It is important for the commissioner to be a change agent, not a bomb thrower," said Peter Pitts, a former associate commissioner at the FDA and the president and CEO of the Center for Medicine in the Public Interest. "If you bring in someone who is aggressively contrary to agency culture, those [career staff] will simply wait him out."

However, if a commissioner can get buy-in from career staff who actually review products, it can "help him accomplish it," Pitts said.

Public Citizen, a consumer advocacy group, has problems with both potential picks.

"I don't know if there is any reason to guess that the president has a real vision for the FDA besides the broad brush deregulate," said group President Robert Weissman. "I think that both of these potential candidates are in line with that. Both of them on the pharma side particularly aim to lower the standard of review for new drugs, presumably for existing drugs as well."

It is not clear who Trump will pick for the FDA. However, several other Cabinet picks have shown that Trump is willing to tap people who aim to radically shake up the agencies they are set to lead.

For instance, Trump tapped former Texas Gov. Rick Perry to lead the Energy Department, an agency he pledged to eliminate while running for president in 2012.

He also chose Oklahoma Attorney General Scott Pruitt to lead the Environmental Protection Agency. Pruitt sued the agency on multiple occasions over several regulations and said that people "are tired of seeing billions of dollars drained from our economy due to unnecessary EPA regulations."

Whomever Trump chooses, Pitts said that he is heartened that names are at least being floated early in the transition.

"A lot of times it is left as an afterthought," he said.
   Read More & Comment...

​21st Century Cures could be the tipping point for Alzheimer’s research

12/14/2016 05:35 PM |

Note:  Today's blog is from the very talented Nicole Gray, formerly a reporter for BioPharmaDive and now an independent journalist who is covering and commenting on the passage and implementation of the 21st Century Cures Act in terms of how it will affect the patient groups that supported it.   Of note is the role The Critical Path Institute will play in ensuring that many of the objectives enshrined in the legislation are realized. 



Yesterday the Alzheimer’s Association was one of hundreds of patient/disease advocacy groups celebrating passage of the Cures Act. From the beginning, when Representatives Fred Upton and Diane DeGette introduced the bill in May 2015, the association rallied long and hard for this legislation, driven by the sense of urgency around Alzheimer’s disease (AD)—the leading cause of death from a disease that can’t be prevented or cured; the most expensive disease in the U.S. and a disease associated with a tremendous personal burden borne by patients and their families.

When Lilly canceled the solanezumab development program last month, it was disappointing, but not a complete surprise. Unlike oncology, AD drug development has been a battlefield where there have been very few victories. 

Between 2000 and 2012, there were 413 AD trials, including 83 phase III trials. While some of these studies tested disease-modifying or immunologic drugs, most focused on treating symptoms. The overall failure rate was 99.6%. There hasn’t been a new drug approved for AD since 2003 when Namenda was approved for symptomatic treatment of moderate-to-severe AD. 

Despite the high level of risk associated with AD drug development, committed companies continue to pursue R&D in this space, but it’s still not enough. As of December 2016, there are 23 drugs in phase 3 development for AD and 134 active trials---a mere pittance compared with oncology in which there are close to 5,000 active drug trials in process, and more recruiting. 

As Jeffrey Cummings from the Center for Brain Health at the Cleveland Clinic noted earlier this year, “Overall, the ecosystem of AD drug development must be altered to yield more targets and more candidate therapies if a robust pipeline of therapies is to be established.”
That’s where the Cures Act comes in. The AD research community stands to benefit in many ways from this eleventh-hour bipartisan feat, especially from the $1.6 billion Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative and the funding of the EUREKA prize competition to spur innovation in AD research.  

Cures is being hailed as groundbreaking legislation, but for AD researchers, many of the law’s built-in initiatives reflect current best practices in Alzheimer’s R&D---large-scale data-sharing, innovative trials design and mega-collaboration. The day after Cures passed in the Senate, the AD research community convened in San Diego at CTAD to listen to a post-mortem recap from Lilly on sola, as well as more encouraging updates from companies like Biogen, which presented phase 1B data showing that adacanumab successfully reduced beta-amyloid plaques in the brains of AD patients; EIP Pharma, which highlighted positive phase 2A data on neflamapidmod in patients with mild cognitive impairment; Eisai with positive phase 1B data on its BACE inhibitor and Sangamo Biosciences, which presented positive, very early-stage data on its gene therapy.

On the last day of the conference, Anavex Life Sciences, a small company with a first-in-class small-molecule, sigma-1 receptor agonist in phase 2A development for mild-to-moderate AD, presented safety and exploratory efficacy data from a 32-patient study on ANAVEX 2-73.  Phase 2A, 57-week data demonstrated a favorable safety and tolerability profile, in addition to positive functional and behavioral outcomes. There were significant improvements in insomnia, depression and agitation, and patients reported feeling happier, being able to play golf again, enjoying international travel and even having more compassion for children.

The presentation’s high point was the cognition data. The data showed early signs of a disease-modifying effect when ANAVEX 2-73 was compared with the current standard of care, with drug-related improvements in attention, working memory, verbal learning and other cognitive domains, compared with declines in the standard-of-care population. And when treated patients were tracked based on MMSE/ADL/CogState scores, after 57 weeks, the scores hovered right around baseline, suggesting cognitive stability.

“This is the first drug to demonstrate statistically significant improvement in cognitive domains. We were able to learn from the vast data available from other AD trials,” said Christopher Missling, PhD, CEO of Anavex.  “We learned from others’ failures and we were able to factor everything that we know about this disease into our development process.”

As a small company, Anavex has been able to leverage data made available through the Critical Path Institute’s Coalition Against Major Diseases (CAMD) to inform clinical trial design. CAMD facilitates sharing of precompetitive patient-level data from legacy clinical trials, and supported development of a clinical trial simulation tool for AD. 

Because of collaborative culture of the AD research community, and the groundwork laid by CPI and other stakeholders, Anavex was able to successfully use adaptive clinical trial design to test their drug in 32 patients and show a statistically significant effect sufficient to justify moving into phase III. 

The Cures Act is intended to create more opportunities for companies to find methods to determine early on whether a drug has what it takes to cross the finish line---and when a drug shows real potential, and meets rigorous safety standards, new drug-development tools will be available to make the pathway to approval more straightforward. 

“I think the legislation is extremely important because it helps to allocate resources. Time is always lost in the interfaces between companies and the FDA. Every day counts,” said Missling.

In reality, implementation of Cures will be slow-moving. Nonetheless, the additional funding and adoption of more innovate trial design could move the target 2025 date for approval of a disease-modifying AD treatment up a year or two, possibly more. 
That’s what twenty-first century victories are made of---pragmatic, collaborative and relentless research that uses new technologies and reserves of knowledge to accelerate drug development and approval. 
  Read More & Comment...

Gray Goose

12/14/2016 09:08 AM | Peter Pitts

My letter to the NY Times ...

To the editor:

Clyde Haberman, in Lives and Profits in the Balance: The High Stakes of Medical Patents (NYT, December 11, 2016) raises an important issue – and then gets it wrong. Patents save lives and enhance the value of medicines. As Abraham Lincoln said, “Patents add the fuel of interest to the passion of genius.” Mr. Haberman points to the Bayh/Dole Act, and suggests that the innovator pharmaceutical industry is getting a free ride on R&D but, according to an article in Health Affairs, drugs with public-sector patents accounted for only 2.5 percent of US prescription drug spending. Also, Haberman refers to the Hepatitis C medicine Sovaldi as costing $1000 per pill. This is incorrect. Every major insurance company and pharmacy benefit manager (PBM) receives significant double-digit discounts from the manufacturer and now, with competition from other innovator companies, prices are dropping even further. That's the power of patents in a free market. The more important question is, why doesn't this result in lower co-pays for consumers? “Facts,” as John Adams said, “are pesky things.”
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"Elusive" RWE

12/08/2016 10:10 PM | Peter Pitts

Pre PDUFA and post 21st Century Cures vote, BioCentury reports that ...

FDA cautious about real-world evidence

A great deal of work will be required to pave the road for the use of real world evidence in regulatory decisions, wrote FDA Commissioner Robert Califf and 14 other FDA staff members in a commentary published Thursday in the New England Journal of Medicine. The article sets a tone of caution just as the 21st Century Cures Act and PDUFA reauthorization goals commit the agency to create a framework for the use of real-world evidence to make decisions about post-approval studies of drugs and their approval in supplementary indications.

The article describes the definition of real-world evidence as “elusive.” The authors believe it refers to healthcare information "derived from multiple sources outside typical clinical research settings, including electronic health records (EHRs), claims and billing data, product and disease registries, and data gathered through personal devices and health applications.”

It warns that the “allure of analyzing existing data may lead to flawed conclusions," and says this “concern is especially salient in light of the growing proliferation of precision molecular medicine and treatments for rare diseases, many of which are anticipated to undergo review in accelerated approval programs.”

Real-world evidence could play an important role in reviewing such applications, the authors note, which adds to the urgency of developing rigorous methods for collecting and analyzing such information. The authors express optimism about "long-term prospects for the evolution of mature, robust methodologic approaches to the incorporation of real-world evidence into therapeutic development and evaluation," but emphasize that "caution is still needed, and expectations of 'quick wins' resulting from the use of such evidence should be tempered accordingly.  Read More & Comment...

So-called Progressives vs Medical Progress

12/08/2016 10:05 PM |

Progressives Against Patients



This week the House and Senate overwhelmingly passed the 21st Century Cures Act.  The legislation increases National Institutes of Health funding, maintains the Cancer Moonshot and Precision Medicine initiatives and provides additional funding for the Food and Drug Administration to support the greater use of information from precision medicine and patient reported outcomes in determining the benefits and risks of new medicines and medical devices.

According to an article by Ed Silverman at STAT: “some consumer advocates and academics warn the legislation contains a provision that may usher in a new era of lower approval standards. 

Here’s why: The bill requires the Food and Drug Administration to develop a program for evaluating the use of so-called “real world evidence” for approving additional uses of medicines, as well as for any follow-up studies that may be required.”

Huh?  How does capturing evidence about the actual clinical risks and benefits of medicines in specific groups of patients translate into lower approval standards.  

Let’s give those who opposed the bill a bit of credit and presume they are uninformed instead of just crazy.  They have no evidence to show that randomized controlled trials guarantee safety or are better at demonstrating effectiveness.  On the contrary, most safety problems are discovered in a haphazard way through adverse event reporting after thousands of uses.  And real world use of medicines provides not information that can be matched against thousands of other data points that randomized trials do not capture.  

In opposing the bill, Public Citizen proclaimed “later-stage “Phase III” trials that have long been the gold standard for drug approval. Well-designed randomized controlled Phase III clinical trials are critical for weeding out bad drugs; more than a third of the drugs that enter Phase III testing fail to gain FDA approval.”

But the “failure” of Phase III trials have little to do with whether or not the drug is safe or even effectiveness at time.  On the contrary, “failure” is a product of being unable to identify reasons for ineffectiveness that would be more accurately and quickly discovered in observational studies.  

Public Citizen has used the gold standard as apolitical tool when convenient.  Michael Carome, MD director of Public Citizen's Health Research Group opposed the approval of Exondys 51 for Duchenne Muscular Dystrophy claiming “It would be a mistake for the FDA to approve this…. It would be giving in to political pressure and essentially eviscerating their standard for approval.... To put out a drug that’s not effective isn’t helping anyone.”   This from a group that has recommended not use ANY new diabetes drug introduced over the past 20 years. 

Ironically, Public Citizen, which now claims randomized trials are the gold standard had fought against their use in testing the effectiveness of HIV drugs in pregnant women living in developing countries.  And some of the groups that were part of the anti-Cures act cabal like Annie Appleseed have pushed for using alternative treatments for cancer that of course undergo no FDA testing at all.  

Similarly, Cures opponents deliberately mislead and misrepresented the truth when they claimed surrogate endpoints -- physical changes or measures that are reasonably likely to predict clinical benefit – leads to ineffective drugs.  Such surrogates are used mostly in a serious or life-threatening disease that lacks good therapies.  As FDA’s Janet Woodcock noted in congressional testimony: “During the last five years (2010-2014), out of a total of 197 novel drugs and original biologics approved across FDA, 84 (43 percent) relied upon a surrogate endpoint for approval. Most of these surrogates have gone on to be well-established tools for measuring drug response or the foundation for biomarkers.”   The talking about weaker standards is as devoid of evidence as it is full of malice. 

The newly found support of randomized trials has nothing to so with watering down FDA standards. It has everything to do with the belief that real world evidence and patient involvement will lead to an increase in the development and use of new medicines and – by extension – benefit drug companies who have a financial interest in getting drugs approved.  

Diane Zuckerman, the President of the far left foundation and trial attorney funded National Center for Health Research -- a woman with little insight and even less expertise about drug development -- pretends to stand up for patients.   She is part of a smear campaign against the hundreds of patient groups that supported Cures Acts, accusing them of being tools of the drug industry.   I will write more on this slander in a future blog.  But for now, let me note that Zuckerman and others like her believe patients can’t be trusted to make such decisions because hope (or pharma funding) clouds their judgment. 

Increasingly medical advances determine not only whether we live or die, but how we will live and die.  Ordinary citizens, those who are potential patients and the friends and relatives of such have as much of a right to determine a drug’s approval as any trial attorney or far left funded lobbying organization.   The anti-Cures Act cabal is more interested in hurting drug companies than in saving lives.   
  Read More & Comment...

Who's next for the White Oak corner office?

12/07/2016 10:09 PM | Peter Pitts

Via Stat News …

President-elect Donald Trump is weighing naming as Food and Drug Administration commissioner a staunch libertarian who has called for eliminating the agency’s mandate to determine whether new medicines are effective before approving them for sale.

“Let people start using them, at their own risk,” the candidate, Jim O’Neill, said in a 2014 speech to a biotech group.

O’Neill, has also called for paying organ donors and setting up libertarian societies at sea — and has said he was surprised to discover that FDA regulators actually enjoy science and like working to fight disease.

A source close to the Trump transition team told STAT that Peter Thiel, the billionaire Trump donor who is helping shape the new administration, is pushing for the FDA appointment for O’Neill, his managing director at Mithril Capital Management.

Trump’s focus on O’Neill was first reported Wednesday morning by Bloomberg.

O’Neill would be an unusual choice. He is not a physician, and lacks the strong science background that nearly all former commissioners have had in recent years.

A graduate of Yale University, with a master’s degree from the University of Chicago, O’Neill went to work at the Department of Health and Human Services in 2002, after a stint as speechwriter at the Department of Education. He worked his way up to principal associate deputy secretary, where he advised the HHS Secretary on all areas of policy, according to his LinkedIn page.

O’Neill first worked with Thiel at Clarium Capital Management, and also ran the Thiel Foundation and Breakout Labs, which funds early-stage companies in areas ranging from food science to biomedicine to clean energy. He is a promoter of anti-aging treatments and technology.

O’Neill also serves on the board of the Seasteading Institute, an organization that aims to create its own sea-based floating communities, on the theory that existing governments are woefully ineffective. “Obsolete political systems conceived in previous centuries are ill-equipped to unleash the enormous opportunities in twenty-first century innovation,” the Seasteading website notes.

O’Neill is not well known in Washington, but has been a frequent speaker on the biotech circuit.

In 2014, in a talk to a group gathered to discuss regenerative medicine, he recalled his days at HHS and expressed disdain for the FDA’s process.
“As a libertarian, I was inclined to believe that the regulatory costs that the FDA impose kill a lot of people and provide a lot of harm to the economy, and I don’t deny that… but one thing that surprised me is that the actual human beings at the Food and Drug Administration like science; they like curing disease and they actually like approving drugs and devices and biologics.”

The problem, O’Neill told the group, is the overall structure and incentives of the regulatory system.

“Every time the FDA commissioner approves something and someone gets sick who used it, the commissioner is summoned to a congressional committee that also controls his budget and forced to testify under oath, why he made this rash decision…It’s a miserable process,” O’Neill said.

O’Neill has proposed that the FDA only require companies to prove drugs are safe before they are sold – not that they actually work.

O’Neill has also said that organ donors should be allowed to be paid. “There are plenty of healthy spare kidneys walking around, unused,” he said in a speech at a 2009 Seasteading conference.

His participation in the Seasteading movement might be a sensitive topic, too. The video of his speech was available on The Seasteading Institute’s website in the afternoon, but by evening, it had disappeared.

In the speech, which is still available elsewhere, O’Neill said that “we can all wish that existing governments will somehow stumble into freedom, but if we want to achieve freedom, seasteads are by far the best prospect.”

Neither O’Neill, Thiel or Trump transition team staffers returned calls seeking comment.

Also under consideration for the FDA job: Dr. Scott Gottlieb, a former FDA deputy commissioner.

Gottlieb, a resident fellow at the American Enterprise Institute, was a senior adviser to the presidential campaign of Wisconsin Governor Scott Walker.  A clinical assistant professor at the NYU School of Medicine, he is a venture partner at the venture capital firm New Enterprise Associates, and a senior principal at TR Winston, a healthcare focused merchant and investment bank. He has testified before Congress 18 times on health and regulatory issues.

Gottlieb was recently named to the transition team.  Read More & Comment...

WSJ Gets It Half Right On Drug Prices

12/07/2016 11:25 AM |

Thomas Sowell observed: “A cynic is said to be someone who knows the price of everything and the value of nothing. The same could be said of economic illiterates, many of whom are in politics and the media”.

But often what is perceived as illiteracy is really confirmation basis or just not understanding.  An example of the latter is WSJ reproter Jonathan Rockoff’s article “Drugmakers Find Competition Doesn’t Keep a Lid on Prices”.  Rockoff's article does transcend the usual narrative:that drug prices don’t decline in the face of competition because only drug companies can defy market forces and pass added costs onto consumers.  Rockoff acknowledges that drug companies are not the only culprits.  In making this point, he still implies competition should reduce drug prices without regard to the costs associated with producing goods or services.   In doing so, he perpetuates the meme that drug companies are so profitable they can cut prices and generate new medicines. 

Rockoff apparently has not looked at the relationship between competition, prices and production costs in other industries.

For example, when has Apple or Microsoft or Google engaged in a price war leading to lower prices over the long run? Have cable rates fallen in response to other ways of watching movies, tv shows, etc?   On the contrary, they have not.  Similarly, has Netflix or Amazon or Hulu reduced their prices as the battle for broadband viewership heat up?  

Have the prices hospitals and insurance companies charge fallen?  How about the cost of college? Or closer to home, why has the Wall Street Journal continued to raise its newsstand and digital subscription prices?  Heck, WSJ is laying off a bunch of high paid writers. Shouldn't prices go lower, not higher?   And why is the renewal price higher than the introductory price.  Shouldn't the $99 price be standard? 

The fact is prices are more than a response to competition.  And competition is rarely only about prices.  WSJ increases prices because the costs of staying in business and putting out a good product increase.   Netflix could have continued to charge 6.99 if it didn’t want to invest in new movies and original programming.  Would people be satisfied watching reruns of Law and Order?  

This dynamic is separate and apart from the increase in list prices that fuel higher rebates for insurers and PBMs.    But not totally.  List prices rise in response to the added cost of rebates and other discounts drug companies must give to get market share.  

As Sowell points out (should he really have to?) “Costs are not just prices arbitrarily put on things. Whether the economic system has prices or not, there are real costs for everything. Whether under capitalism, socialism, feudalism or any other system, the real cost of building a bridge are all the homes, factories and other structures that could have been built with the same labor and materials that went into building the bridge.’

To be sure, rebates and discounts don’t mostly flow to the consumers of the drugs generating rebates and discounts.  But that is due to the control insurers and PBMs have over retail pricing.  This is a huge problem as I have pointed out time and again.  Until recently most reporters were unaware of how rebates worked.  (Credit due to me and Peter for doing the explaining!) 

None of the above changes the fact that lower prices can often lead to less innovation across industries or that prices do reflect value in market economies. Generic drug companies don’t innovate and often stop producing essential medicines that go off patent because prices are often drop below increasing production costs. 

Rockoff, like many of us, seek explanations when competition doesn't lead to lower prices.   The key is to look deeper into how competition sustains innovation.  Companies compete on quality, on novelty and on value.  Prices reflect what those qualities or values are as well as the cost of making them.   If we want 1990s prices for anything, college, cellphones or drugs, be prepared for 1990s technology.  
A footnote:  Rockoff’s piece is featured in a WSJ weekly business ethics course reviewed by OC Ferrel, a professor of business ethics at Belmont University.  Ferrel writes: “Students should understand that 'fair' competition should result in competitive or lower prices. This phenomena (sic) is causing increased burden on the health care system and should have public policy consequences.”

Maybe Sowell was not tough enough.  Read More & Comment...

21st Century Cures: PDUFA Jr. or PDUFA Plus?

12/07/2016 02:03 AM | Peter Pitts

The 21st Century Cures Act provides a legal foundation for regulatory innovations including approving supplemental indications based on real-world evidence and approving antimicrobial drugs for limited populations. The bill also would help FDA recruit and retain staff by creating mechanisms for it to pay salaries that are competitive with those offered in the private sector.

Other key provisions include:

* Real World Evidence. Require FDA to establish a framework for use of real-world evidence to approve supplemental indications and satisfy post-approval requirements. Timeframe: Within 2 years

* Healthcare Economic Information. Clarify ability of manufacturers to discuss pharmacoeconomic data with payers, formulary committees and others. Timeframe: Immediate

* Limited Population Pathway. Allow limited approval of antimicrobial drugs for life-threatening infections; require labeling and advertising to include “Limited Population” language. Timeframe: Immediate

* Summary Level Review. Allow approval of new indications based on data summaries from sponsors (sponsors must also submit full data). Timeframe: Immediate

* Accelerated Approval for Regenerative Advanced Therapies. Create regenerative advanced therapy designation that allows accelerated approval and use of clinical evidence, clinical studies, registries or other real-world evidence to satisfy post-approval requirements; require FDA to explain decision not to grant regenerative advanced therapy designation. Timeframe: Immediate

* Qualification of Drug Development Tools. Establish review pathway for biomarkers and other drug development tools to shorten development and reduce failure rate. Timeline: Draft guidance within 3 years; final guidance 6 months after end of comment period

* Reauthorization of Program to Encourage Treatments for Rare Pediatric Diseases. Reauthorize the pediatric rare disease Priority Review voucher program until 2020; a drug designated by Sept. 30, 2020 could receive a voucher if approved before Sept. 30, 2022. Timeframe: Immediate

* Silvio O. Conte Senior Biomedical Research Service. Increase senior biomedical research service positions to 2,000 from 500, allow FDA to deploy biomedical research service members for product assessments, increase maximum salary to president’s salary. Timeframe: Immediate

* Hiring Authority for Scientific, Technical, and Professional Personnel. Allow FDA commissioner to set salaries for scientific, technical, or professional positions at up to the president’s salary. Timeframe: Immediate

* Patient Experience Data. Require statement upon drug approval about FDA’s use of patient experience data collected by patients, caregivers and their representatives; disease research foundations; researchers; and drug manufacturers. Timeframe: 180 days

* Patient-Focused Drug Development Guidance. Require FDA guidance on how to collect patient experience data for use in regulatory decisions, how patients can submit proposals and how FDA will respond to them, and how FDA plans to use such data. Timeline: Initial plan in 180 days; draft guidance within 18 months; revised or final guidance 18 months after end of comment period

* Expanded Access Policy. Require companies to have publicly accessible compassionate use policies for investigational drugs treating serious or life-threatening conditions. Timeline: 60 days

On the down side, the $500 million of funding is not mandatory. Stay tuned.

For an excellent recap of the legislation, have a look at BioCentury’s Steve Usdin’s excellent article. Per Usdin, “The political process has created a consensus bill that lacks the kind of paradigm-shifting changes its authors promised. But Cures would produce real, though modest, forward motion in several areas that are important for translating scientific advances into new therapies.”

And, importantly, “Critics of the 21st Century Cures Act have warned that it would erode approval standards by allowing FDA to approve drugs based on anecdotal evidence. This is a huge exaggeration. What Cures would do is start FDA down the long road toward relying on real-world evidence to support selected regulatory decisions.”

Bravo.  Read More & Comment...

Two Patients Overcome Illness To Take On ICER

11/20/2016 11:48 PM |

The best way to measure the value of medical progress is to find out what people fighting serious chronic illnesses do as they get stronger and healthier.   

When two people going on different journeys in overcoming potentially life threatening diseases and wind up on a common mission --  to battle against health care policies that deny well-being to others --  you know that value cannot be defined simply as what saves health insurers money. 

Don Wright was diagnosed with multiple myeloma in 2003 just ran his 100th marathon.   He has been taking one pill a day since then to keep the disease in check and now, with the latest addition of another medicine, he is making his centennial run without missing a stride.   When he not running or practicing law, Don provides other people with cancer support and guidance.  

Dani Yevsa was diagnosed with psoriatic arthritis. Denied newer medicines by her insurer, she had to try older drugs first. Unable to move, let alone work, her husband quite his job to care for their four children.   To get the care and medicine they needed to stay alive, went on welfare.   Medicaid where she was forced to fail on three treatments that made her sicker, not better.   
She is finally on medications her doctor prescribed.  

Both Don and Dani took different approaches to the same path.  They are making thousands of patients around America about an insurance funded organization called The Institute for Clinical and Economic Review (ICER).  ICER states it is “a trustworthy, independent source to help assess how valuable a new drug really is.”  And it claims its goal is to make innovative drugs affordable to patients and insurers.  

Except that ICER has decided Don and Dani should only get the older drugs that would have left him disabled or dead.

ICER is deciding for Don, Dani and millions of other patients how much their lives are worth, not the other way around.  And ICER has decided that the benefits new drugs provide healthy people are MORE valuable than life-years gained by those who are chronically ill or disabled. Similarly, Dani and Don are worth less according to ICER’s economic assumptions, because they are less likely to get as much benefit from medicines than people with more treatable conditions.  And finally, ICER assumes that future benefits are less valuable to Dani and Don than to others.   

So it’s no surprise that ICER concludes every new medicine isn’t worth paying for unless they are deeply discounted off retail price and save money by reducing the use of other medical services.  

ICER responds that it’s trying to find prices that patients can afford first and foremost.  But the deeper discounts they recommend don't make medicines affordable or free up cash. In the real world of how PBMs and insurers price drugs, the savings go to PBMs and insurers, not patients. At the same time, insures overcharge customers for prescription drugs by making them pay up to 50 percent of the retail price of the drug.  ICER has issued over a dozen studies and never once wrote or spoke about passing these savings to the patients.  

Additionally, ICER suggests that to save even more money, insurers limit the number of people who have access to these new life extending medicines.  ICER believes that spending more than $900 million a year on a new medicine should set off alarm bells that strong action – capping how many people can get the novel treatments – must be taken.   For psoriasis, ICER concludes that health plans can only cover about 35 percent of the 183000 people diagnosed with psoriasis could be treated with before potential budget impact reaches $904 million.  For multiple myeloma, ICER caps access at 25 percent.

That means they before they can get these new drugs, if ever, they have to take older drugs and get sicker.   That means, over 5 years, ICER would deny 44000 people with myeloma a second and third chance at life and cost 88000 life years. Over the same time period, given the mortality rate associated with older psoriasis drugs, about 52000 life years would be lost.   Dead patients cost nothing. 

Don and Dani and others already pay thousands in premiums and taxes only to be denied new medicines based on the kind of rationalizations ICER produces. They have ICER in their sights because the more its recommendations spread, the more money health plans make at the expense of people they often impoverish when they are most vulnerable. 

ICER defines value as what’s most profitable for PBMs and health plans. It devalues what makes medical progress so important: When you’re seriously sick, it’s hard to plan or hope. Our dreams our diminished and deferred.  We are forced to forsake our full potential. 

ICER claims such benefits can’t be counted because they can’t be quantified.  I think we can easily measure the value of medical progress: Value is what Don has achieved, what Dani has fought for and the path they are forging for everyone who is or may be forced to fight disease  Read More & Comment...

CREATES Act should be created equal

11/15/2016 08:28 AM | Peter Pitts

From today's edition of the Washington Times:

Taking risks with drug safety

Congress must remedy the Creates Act before passing it

Over 60 percent of Americans want the government to take action to lower prescription drug prices, according to a new Kaiser Family Foundation survey. Congress, for once, is listening to voters.

Lawmakers are pushing forward with the Creating and Restoring Equal Access to Equivalent Samples (Creates) Act. The bill’s sponsors hope a series of new legal provisions will make it easier for drug companies to introduce generic alternatives, thus spurring competition and bringing down prices. The bill is well-intentioned. Unfortunately, it’s also worded extremely poorly. Instead of bringing generics to market sooner, the bill could endanger patients’ lives and encourage costly, needless litigation.

The proposed law would address conflicts between innovator drug companies and their generic competitors. To protect consumers, the Food and Drug Administration requires that new drugs undergo a series of clinical trials to prove their safety and effectiveness before entering the market.

Generic drugs must also complete clinical trials, but only to prove they’re clinically similar to the already-approved brand-name drug. The generic drug creation process inherently requires that manufacturers obtain brand-name drug samples from innovators for comparative testing.

Many drugs are so potent, or have such dangerous side effects, that the FDA requires drug companies to develop and abide by specialized safety protocols called “risk evaluation and mitigation strategies,” when selling or dispensing these medicines.

For example, Soliris, a drug used to treat rare blood disorders, can potentially cause dangerous bacterial infections in the bloodstream. Because of these possibly fatal side effects, the FDA-approved risk evaluation and mitigation strategy requires that only specially certified physicians can prescribe Soliris, and that patients must be given an information card to help them recognize early warning signs of an infection.

Here’s where it gets complicated. Generic drug companies are accusing brand-name manufacturers of dragging out negotiations regarding these risk evaluation and mitigation strategies to avoid handing over drug samples. Without the samples for comparative testing, generic manufacturers can’t enter the market. And without competition, the brand-name manufacturers get to keep selling their medicines at inflated prices, even after the patent has expired.

That’s why some in Congress want to pass the Creates Act. The bill would allow generic drug manufacturers to sue brand-name manufacturers if they fail to hand over their drug samples for testing within 31 days, or if the companies do not reach an agreement on shared risk evaluation and mitigation strategies for risky drugs.

That sounds reasonable. Nobody wants brand-name companies to drag their feet and keep prices higher longer than necessary. But the Creates Act’s language is so imprecise that it could lead to potent medicines falling into the wrong hands, without adequate safeguards for patients.

The bill strips the FDA of its watchdog role. Under the proposed law, generic manufacturers aren’t required to outline testing and safety protocols for the FDA to approve. Even if a generic drug maker’s proposed risk evaluation and mitigation strategies are inadequate, the FDA has no authority to reject or halt the transfer of medicines to the generic company for testing.

The experts at the FDA would have no choice but to approve the transfer within 90 days, even if they think doing so would put patients in danger. The Creates Act would also be a trial lawyer’s dream come true.

Poorly worded liability provisions subject innovators to unfair legal risk. Generic drug companies often obtain brand-name drug samples and ship them off to third-party research firms to perform clinical trials. If the third party is negligent with the samples, patients could get hurt. Under the bill’s terms, patients would be able to sue the brand-name drug company, even though it had no control over the testing or safety protocols.

The bill also lets generic drug companies sue innovators for not handing over samples within 31 days of a request, even if both companies are actively negotiating the terms of the sample distribution and safety protocols.

And though the proposed law requires innovators and generic companies to strike transfer deals on “commercially reasonable market based terms,” the law doesn’t clarify what that means. Such subjective wording is music to trial lawyers’ ears.

Congress deserves praise for trying to bring generic medicines to market faster, thereby relieving consumers from high drug prices. Yet good intentions don’t change the fact that the Creates Act, as constructed, is deeply flawed. Congress could help consumers by reworking the law to ensure it stops isolated bad behavior without gutting safeguards for patients or enabling unscrupulous trial lawyers to file costly, pointless suits.

Peter J. Pitts, a former FDA associate commissioner, is the president and co-founder of the Center for Medicine in the Public Interest.
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The PBM Sky Hook

11/08/2016 03:35 PM | Peter Pitts

From today’s edition of the East Bay Times …

Patients threatened by new drug coverage limits

Kareem Abdul-Jabbar’s toughest fight wasn’t on a basketball court.

In his early 60s, the six-time NBA champion was diagnosed with leukemia, the deadly blood cancer. Fortunately, Abdul-Jabbar had access to state-of-the-art medications, including the advanced drug Tasigna, which paralyzed his cancer cells and prevented further growth. Today, eight years after his initial diagnosis, Abdul-Jabbar is thriving and cancer-free.

Unfortunately, many of today’s leukemia patients won’t be so lucky. CVS Health, the nation’s second-largest pharmacy benefit manager that oversees 65 million Americans’ drug plans, recently rescinded coverage for Tasigna –— and 130 other specialty drugs.

As a result, millions of people could be denied access to drugs that could save their lives. Instead of prescribing the medicines best-suited to patient needs, physicians will be forced to recommend lower-quality treatments.

Pharmacy benefit managers, or “PBMs” for short, administer the prescription drug plans used by health insurers and employers. In recent years, these organizations have gotten stingy about which drugs they cover.

Back in 2012, the nation’s largest PBM, Express Scripts, excluded no medicines from its list of covered drugs, while CVS Health left off about 30. Today, they exclude more than 200, including an array of popular treatments for arthritis, Hepatitis C, and various skin conditions.

PBMs have also stopped paying for cutting-edge cancer treatments. In addition to Tasigna, CVS won’t cover the revolutionary prostate cancer treatment Xtandi. Meanwhile, Express Scripts just stopped covering Zyclara, a cream that can help prevent skin cancer.

PBMs are restricting drug access in other, more devious ways as well.

CVS is also steering patients away from ultra-complex “biologic” drugs, forcing them to switch to lower-cost treatments the company claims are medically equivalent. But in many cases these less expensive therapies, known as “biosimilars,” aren’t approved by the FDA to be interchangeable with their brand name alternatives.

Consider one study that compared the effectiveness of a Crohn’s disease treatment and its biosimilar. An alarming eight in 10 patients who took the biosimilar required a hospital readmission for additional treatment, compared to only one in 20 who took the original drug.

Despite these disturbing results, PBMs are comfortable forcing patients to use biosimilars and generic medications. That’s because their only concern is bringing down short-term drug spending — even if those savings come at a cost to patients’ well-being.

Ironically, this strategy will end up raising health care costs in the long-run. If doctors can only prescribe less-effective treatments, folks will get sicker, be hospitalized more frequently, and require more expensive care. That demand will drive up overall healthcare costs and overwhelm doctors and hospitals with waves of new patients.

That doesn’t matter to PBMs, though. A dollar saved by avoiding top-notch drugs is a dollar that goes into PBMs’ pockets — even if the patient becomes sicker on less effective treatments and racks up much larger hospital bills for insurers and patients to pay down the road.

PBMs coverage denials are a deadly prescription for America’s patients. By shrinking coverage for cutting-edge treatments, PBMs are forcing sick people to use substandard drugs. It’s about time patients mount a full-court press against this callous behavior.

Peter J. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.  Read More & Comment...

Alta Vista

11/04/2016 08:14 AM | Peter Pitts

As they say, everything you read in the newspaper is true -- except for those things you know about personally.

According to the latest report from the Altarum Institute, “moderate 2016 health spending growth continues a slow downward trend.” Unfortunately this doesn’t fit the narrative of those who want to talk about runaway trains – especially for pharmaceuticals.

Here are the numbers: Hospital spending represents 32% of American healthcare spending, 20% goes to physician and clinical services, 15% goes to “other health spending,” and 10% is for prescription drugs.

If the media had covered this story -- which they have not -- the headline would have been, "Pharmaceuticals represent 10% of American healthcare spending. A dime on the dollar. A smaller percentage than almost every nation in Europe."

And here’s the subhead – Spending on pharmaceuticals is growing at a slower rate (under 4%) than either hospital (just under 5%) or physician costs (just over 5%). This breakdown is based on the Bureau of Economic Analysis monthly spending data, including its most recent update released on August 29th of this year.

While pharmaceutical spending seems to be the only issue of interest to the media and politicians, the Altarum account isn’t the one they’re telling. Almost every story and every speech on the drug sector focuses on price without the context of value, using a few bad actors to represent the entire industry. Unfair? Sure -- but life is unfair. There is, however, no excuse for slanted stories and untrue, accusatory political oration.

Disease is the enemy. Practicing physicians know this, but their professional association – the American Medical Association – seems in need of some education. The AMA’s new program, “truthinrx.org,” is entirely silent on the actual metrics of healthcare spending and the value of pharmaceutical innovation. Ignorance is not bliss.

Healthcare innovation saves lives, saves money, promotes economic growth, and provides hope for hundreds of millions of people (both patients and care-givers) in the United States and around the world. It deserves respect – or at least honest reportage.

Does this sound naïve? Perhaps, but as Schopenhauer said, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.”

The complete Altarum report can be found here.
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Insurers to CMS, Congress: We Want More Rx Rebates So Give Us Total Control Over Medicare Drug Benefit

11/02/2016 12:54 PM |

A recent article in MedPage - Insurers to CMS, Congress: For Lower Rx Costs, Hand Us the Reins – needs a bit of translation to help people under stand what handing insurers the rein over what drugs and how much to spend really means.   For instance, the headline should actually read "Insurers to CMS, Congress: We Want More Rx Rebates So Give Us Total Control Over Medicare Drug Benefit" 

According to Medpage: “Congress and the administration can help rein in rising drug costs through a few key regulatory and legal fixes, said insurers and pharmacists at AHIP's National Conference on Medicare, Medicaid and Duals on Tuesday.”

"I think plans need to be given a little bit more leeway to truly assess the value of drugs to make a decision: does this drug at the cost really provide any additional value?" said Sarah Marche, PharmD, vice president of pharmacy services at Highmark, a Blue Cross affiliate in Pennsylvania.

Translation:  We already limit access to life saving medicines for the most chronically and seriously ill seniors based on our current value assessment.   But we want even more control over what patients get.   And by ‘additional value’ we mean increasing the 35-40 percent price discounts we get and what consumers are charged.  We want more. 

Marche noted that not every drug Medicare covers adds value.
"Glumetza [a branded version of metformin] provides no value above and beyond what's available, and if you look at a lot of the commercial formularies, it's blocked," she said. "Nobody's dying. Nobody has any huge issues with that, but we don't have that same flexibility within the Medicare space. So, you're covering a drug that really provides no additional value, just increasing the cost."

Translation:  After Valeant got hammered for hiking Glumetza by more than 800% in 2015, the list price of  stood at $10,020 for 90 tablets, up from $896 in January 2013,.  For the longest time, insurers didn’t complain  .  Half of Glumetza’s price is  given back in discounts, rebates, chargebacks, and the like to wholesalers, managed care organizations, pharmacy benefit managers, federal and state healthcare programs, and others. 

 Under pressure to reduce prices, Valeant gave Walgreens’s an exclusive deal to sell Glumetza as generic prices.  So Express Scripts, the company running our drug benefit decided it could turned around an blocked Glumetza and cutting a deal with a company making a generic version of the drug to make up for the lost rebate revenue.  So we would have covered it if had provided additional profit… I mean value to us regardless of cost.  It really depends on the rebates Express Scripts can share with us.  

Another panelist, Mark Owen, MBA, president of government programs for the the Blue Cross-affiliated Health Care Service Corp., power “to limit beneficiary access to specialty pharmacies.” 

While Owen noted that critics of the idea have said such a change could pose access challenges, he argued that allowing plans to direct beneficiaries towards only certain pharmacies could lower costs and increase adherence.

Translation:   Limiting access allows us to pocket more money because it  ensures  patients have no choice but to take the drugs that we give them.  That way we make the biggest profit margin whether they like it or not.  And we know that charging patients about 40 percent of the retail price of products is a good way to force them to use drugs what give us the biggest margin.   We will work really hard to increase adherence, but only with drugs that fatten our bottom line regardless of whether the drug works for that patient or not.




 
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Abusing the Privilege?

11/02/2016 07:37 AM | Peter Pitts

From Medpage Today ...

FDA, Industry Focus on Abuse-Deterrent Opioids

No consensus immediately apparent after 2-day meeting

FDA officials and representatives from both the generic and branded drug industries spent two days hashing out next steps for development of abuse-deterrent opioids.

The two topics on the table: reviewing a draft guidance for the development of generic versions of abuse-deterrent opioids, and developing standard in vitro testing methods to characterize a drug's abuse-deterrent properties.

The meeting was in line with FDA's strategic plan for mitigating the opioid epidemic, which it released in February 2016, said Douglas Throckmorton, MD, deputy director of regulatory programs at the FDA's Center for Drug Evaluation and Research. That includes incentivizing the development of "progressively better" abuse-deterrent opioids and supporting a transition to these products, he said.

Throckmorton acknowledged the tension between generic and branded developers, but advocated working together to come up with a solution that benefits all parties.

"If you all came up with a single approach that suits the best product development, we would be delighted and take it very seriously," Throckmorton said. "It would move the field a great deal. It would require careful collaboration, but it's been successful in other fields, like drug-eluting stents, which had a similar challenge but the industry pulled together and made suggestions we all make use of."

FDA released its draft guidance for evaluating generic abuse-deterrent formulations last March, with the goal of ensuring that a generic is no less abuse-deterrent than the brand-name opioid. No generic abuse-deterrent opioids are currently approved.

In general, an ANDA applicant isn't required to provide independent evidence of the safety and effectiveness of the generic drug; instead it relies on the FDA finding that the previously approved product is safe and effective and must demonstrate that the generic is "bioequivalent" to the reference drug, primarily on the basis of pharmacokinetic studies.

Robert Lionberger, PhD, director of the office of research and standards in the FDA CDER's office of generic drugs, noted that the ANDA for any generic abuse-deterrent opioid would cover all routes of abuse: oral, nasal, injected, and smoked. It would also evaluate the drug in comparative in vitro studies and, in some cases, in relevant pharmacokinetic or other studies to show it is no less abuse-deterrent.

But some industry voices -- particularly from the branded industry -- said these assessments did not go far enough.

"I am concerned that this draft guidance is not sufficient to ensure that generic versions will be no less abusable than the reference drugs," said Alexander Kraus, PhD, of Grunenthal USA in Morristown, N.J. "It does not do enough to ensure that the generic meets therapeutic equivalence. It can't be based solely on in vitro testing. I encourage the FDA to require not only Category I in vitro tests, but Category II pharmacokinetic and Category III human reference studies as well."

Those Category I in vitro tests for abuse-deterrent opioids have their own issues to be worked out, which was why they were also a focus of the meeting.

Xiaoming Xu, PhD, a senior staff fellow at the FDA's division of product quality, said in vitro testing for abuse-deterrent opioids has not been standardized, making both comparisons with other drugs and overall assessments challenging.

Ideally, that testing should assess each potential route of abuse -- oral, injectable, nasal, and smoking -- starting with simple and gentle mechanical and chemical manipulations, progressing to complex and more destructive manipulations. It should also address mechanisms by which abusers can be expected to attempt to overcome abuse-deterrent properties as well as the ways that patients may alter the formulation to change the amount of of drug that gets released, Xu said.

The challenge is that the design of these experiments is complex: any single product can have more than a dozen possible methods to achieve a desired manipulation; scores of different solvents; different reactions to various temperature conditions; different volumes released, and so on. Indeed, the number of experiments can run into the thousands, Xu added.

The problem garnered unique observations about the automobile industry and coffee grinders. Richard Lostritto, PhD, acting associate director in the office of policy for pharmaceutical quality at FDA's CDER, noted that the auto industry standardized the type of hammer it would use in safety tests; Karsten Lindhardt, PhD, of Egalet Corporation, noted that he's had to buy several different types of coffee grinders to do proper in vitro testing.
"You end up with each material behaving differently," he said. "One grinder may be optimal for one drug but not for another."

Throckmorton acknowledged the tension between developing standardized versus individual tests for these types of analyses: "We've seen that even small changes in some formulations can have a large effect on product performance."

Although it was not a point of the meeting, critics at past FDA advisory committee meetings for abuse-deterrent opioids have called for epidemiologic data on whether or not these formulations can actually reduce abuse and the more serious consequences of addiction, overdose, and death.

Also, the meeting did not address patent issues, which generally fall outside FDA's jurisdiction. Although the major opioid drug compounds are now off-patent, it may be many years before patents expire on the specific abuse-deterrence technologies now in use.  Read More & Comment...

Lancet Oncology takes on Pharmacovigilance

11/01/2016 11:24 AM | Peter Pitts

The November issue of Lancet Oncology focuses on pharmacovigilance and drug safety. The lead editorial drives home some key points:

At a time when the number of biological agents due to come off patent is increasing, and in the face of a market fuelled by escalating drug prices and pressure from pharmaceutical companies and patient groups alike for expedited drug approval, issues surrounding the safety and efficacy of agents such as biosimilars and generics are paramount.

Substantial variation exists between high-income and low-to-middle-income countries with regards to manufacturing and supply chain regulation of generic drugs, despite countries such as India providing a large market share of generic drugs worldwide. Moreover, bioequivalence—a key consideration when comparing generic formulations with their trademarked counterparts—can vary substantially, making appropriate regulation particularly important. Issues of safety and regulation are further compounded when approving biosimilars: despite nearly 10 years’ of experience in dealing with biosimilar agents, regulators still need to streamline and expedite approval processes, and improve ways of reducing cost. Thus, taken together, the importance of pharmacovigilance has never been greater.

Given that multiple health-care systems encourage or enforce generic and biosimilar prescribing, sometimes without physician knowledge or consent, coupled with further potential complications created by generic or biosimilar switching during a course of treatment, pharmacovigilance needs to evolve beyond merely the uncovering, monitoring, and reporting of adverse events, to continual pre-marketing and post-marketing surveillance.
Although a focus on regulatory and policy issues is key to monitoring safety and     efficacy, especially for newer agents, there are other ways in which drug safety can be improved.

The November issue also includes my new paper, 21st century pharmacovigilance: efforts, roles, and responsibilities.

Here’s the abstract:

In an era when the number of expedited and conditional review pathways for newly available brand-name drugs and biosimilar medicines to treat serious and life-threatening diseases is increasing, defining pharmacovigilance has never been more crucial. 21st century pharmacovigilance is not merely about uncovering, reporting, and addressing adverse events associated with already approved and marketed agents, but can be described as the systematic monitoring of the process of pre-market review and post-market surveillance, which includes the use of medicines in everyday practice. Pharmacovigilance identifies previously unrecognised adverse events or changes in the patterns of these effects, the quality and adequacy of drug supply, and should ensure effective communication with the public, health-care professionals, and patients about the optimum safety and effective use of medicines. In this paper, the first in a Series of three about drug safety in oncology, we discuss evolving challenges in the purview, roles, and responsibilities of the US Food and Drug Administration and the European Medicines Agency with respect to pharmacovigilance efforts, with a special emphasis on oncology treatment.

If you’d like a copy of this article, please contact me at ppitts@cmpi.org.  Read More & Comment...

ICER Counts Lung Cancer Patients as 2/3 of a Healthy Person

10/26/2016 01:01 PM |

ICER released a report claiming that at retail prices,  immunotherapies (Tecentrig, Keytruda and Opdivo)  for non small cell lung cancer (after a first line of treatment) are not worth using compared to a 20 year old drug (docetaxel) that is 3-4 times less likely to help patients and when it does work, is half as effective in extending life and generating a treatment response.   The table below shows the significant clinical benefits of new drugs that block PDL-1 and PD-1 protein expression, 
 

Drug	Ratio of Patients Likely to    Benefit from Immunotherapy Compared to Docetaxel	Expected Survival in Months	Differnce in Duration of Response in Months
Docetaxel		8.5
Acentriq	3.4	14.8	7.2
Opdivo	4.0	11.1	11.6
Keytruda	3.8	19.4	Not reached

  Source: Institute for Clinical and Economic Review, Evidence Report - Non-Small Cell Lung        Cancer, Table 6 page 36 and Table 10 page 45

ICER determined that the maximum amount of money to be spent on an additional year of life in perfect health -- a quality adjusted life year (QALY) is $150K.   Which means that most of the new drugs developed and to extend the life of lung cancer patients over the past ten years would not be used. 

Applying the ICER QALY calculations to lung cancer patients over the past ten years, I found that if ICER had its way 10 years ago, and denied access to new lung cancer drugs, today the death rate from lung cancer would be 23 percent higher.  And the cost of care will be more expensive, increasing hospital related costs by $3 billion a year.

ICER ignores indirect costs, such as lost productivity and caregiver salaries or the productive possibilities of being able to make plans to marry, raise kids, compose music, travel, go to school. ICER ignores the value of two additional years of life to a patient who has run out of options.

But the worst element of the ICER framework is how it devalues the additional months and years of life people with advanced lung cancer can get from newer medicines.  

At face value ICER’s QALY standard of value is arbitrary. Patients who live twice as long as those taking a generic drug should be credited with the total years of extended life.  ICER believes that an additional year of life for a lung cancer patient is really worth two-thirds of an additional year of life for a healthy person.  

        


Where has this metric been used before?    Article 1, Section 2, Paragraph 3 of the United States Constitution, which allowed slave states and their collective slave drivers to count each of their slaves as 3/5 of a white man.  

To mind the use of a QALY in determining access and drug prices violates the spirit, if not the letter of the Equal Protection Clause.

Worse (perhaps)ICER uses that same discriminatory rationale by assigning a lower value to patients and a higher value to insurers.   When it comes to patients, ICER uses the retail price of the drug to determine a QALY   When it comes to payors,  ICER uses the price or cost of the drug LESS any cost savings generated. 
 

Immunotherapy	Payer Cost per patient  net of drug generated savings	Cost used for patient QALY
Tencentriq	39000	102519
Keytruda	73900	108841
Opdivo	44500	180489

ICER is the worst example of how economic analysis has been applied to health care.  In the end, it is not about numbers. It is about people and the additional years and vitality medical innovation generates.  ICER is not alone in failing to factor in the economic value of hope or the virtue of forward looking, of having a project.

Modern medicines are extending lives, improving lives and saving lives. Setting an arbitrary limit on what that is worth is simply closing the door on medical progress, increasing the death rate and driving up costs at the same time.  And it also forecloses the possibilities of life that, while intangible or uncounted, adds more to our well-being than consumption.  As the great economist Irving Fisher noted: The true “wealth of nations” is the health of its individuals. And greater health through the diffusion of medical innovation is the most important way to eliminate inequality and eliminate barriers to people battling disease. ICER's value framework diminishes the value of longer life as part of an effort to show most new drugs are NOT cost effective.   In doing so, it is violating the civil rights of people because they have lung cancer.   



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Bernie's Terrible Tweet

10/23/2016 08:34 PM | Peter Pitts

In a recent tweet, Senator Bernie Sanders made it clear he’s upset about high drug prices. Less clear is that his righteous wrath will put patients in harm’s way.  He proved yet again he’s uninformed about the facts and unconcerned about the unintended consequences of his actions.

The target of Senator Sanders terrible tweet was a small innovative pharmaceutical company (Ariad Pharmaceuticals) and its innovative drug Iclusig (for chronic myeloid leukemia treatment). The company raised the price – and Senator Sanders can’t see why. He should open his eyes.

A few facts that are worth sharing. The first is that Iclusig serves a population of approximately 1,000 to 2,000 patients. And these patients have limited options. Ariad Pharmaceuticals, works to ensures that no patient is prevented from treatment due to price. (They provide a robust support program for patients who have accessibility and affordability concerns.)

Second, these types of ultra-orphan disease cancer patient population programs require large investments and face tremendous odds.  Ariad sure doesn’t look profitable. They’ve invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion since the company was founded. But they’re betting on innovation. In 2015, Ariad generated $119 million in total revenue and invested $171 million, or 143% of revenue, in R&D alone.

Third and most importantly, Iclusig works.  It significantly increases 10-year survival rates for patients with no other hope or option except for expensive stem cell transplants and draconian radiation treatments.

Attention Senator Sanders. It’s not just a question of an ecosystem-driven price. It’s also about investment and value – precisely the rationale behind the Orphan Drug Act -- to encourage investment in treatments for small and in this case, tiny, populations. “Facts,” as John Adams quipped, “are pesky things.
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Fact Checking Hillary on Drug Pricing

10/23/2016 08:30 PM | Peter Pitts

As seen in the Daily Caller

Fact Checking Hillary Clinton On Drug Pricing

Both Donald Trump and Hillary Clinton get a lot of flak for lying. But in Secretary Clinton’s latest speech on healthcare reform, she didn’t lie — she just got all her facts wrong.

Clinton used her speech to demonize pharmaceutical companies. She argued that greedy firms are gouging consumers and that government-imposed price controls are needed to protect us from them. Her rhetoric ignores reality and her proposals would harm the patients she wants to help.

According to Mrs. Clinton, Americans are “paying the highest price” for medicines, compared to citizens of other developed nations.  She implied that drugcompanies are overcharging Americans just because they can. It’s not so simple.

The real reason medicines are more expensive in the United States is that the socialized medicine systems in other countries cap prices on innovator drugs, while also rationing their use. Many foreign governments threaten to break ‘drug patents if firms don’t agree to sell their products at below-market rates. As a result, American consumers shoulder a disproportionate share of the world’s research and development burden. That’s “free-riderism” and it’s not fair. It’s also important to note that generic drugs, which account for 85 percent by volume of all the medicines used in the United States, are cheaper here than in Europe or Canada.

 But the answer isn’t to impose our own price caps. That would only discourage research into new medicines. Here’s a fact that Clinton didn’t mention — America invents more than half of new medicines in the world.  Stifling U.S. research would lead to vastly fewer medicines here and across the globe. It’d be smarter economically, and better for patients, to negotiate stronger trade protections to prevent other nations from freeloading off American investments.

Secretary Clinton told her audience that their tax dollars fund drug safety evaluations. They do not. All of the complex and costly clinical trials that must be done to bring a new medicine to market are fielded and funded — 100 percent — by the pharmaceutical industry. They are then reviewed by the Food and Drug Administration. And industry pays for that privilege through “user fees” the FDA collects from pharmaceutical companies.

She also slammed the Medicare Part D drug benefit, touting a doctor’s claim that he “can’t prescribe certain drugs that [his] patients need” because government health programs won’t pay for them. But when it comes to Medicare, that assertion is simply false. Medicare’s prescription drug plans cover, on average, 191 of the 200 medicines most used by seniors.  That’s more than most Obamacare exchange options.

In her assault on capitalism and private enterprise, Secretary Clinton singled out the price of hepatitis C drugs. She claimed that makers of these cures — which are vastly more effective than previous therapies — are gouging Americans.

The truth is radically different – and highly documented. Hepatitis C drugs are now cheaper in the United States than in Western Europe, thanks to a price war between competing manufacturers.  Clinton inadvertently picked an example that proves the free market yields better, cheaper medicines than socialist systems and fix prices and ration care.

Bashing the companies that research and produce the world’s most groundbreaking medicines might give Clinton a bump in the polls. But her reality-free rhetoric has dangerous consequences.

Clinton’s attacks on drug makers have prompted a sell-off of biotech stocks multiple times over the past year.  If companies can’t raise funding from investors, they’ll have to limit new research projects. That means fewer drugs down the road. What’s political expediency worth?

And if Clinton reaches the White House and actually implements price controls, it’s statistically certain Americans will lose out on lifesaving drugs. Price controls in other countries depress research spending by up to $8 billion each year — the equivalent of three or four new drugs, according to a Department of Commerce study.

For a super policy wonk, Secretary Clinton got an awful lot wrong in her recent speech. If she really wants to help patients, perhaps she should pay a little less attention to her focus groups and a little more attention to the facts.

Peter J. Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest. 
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Clinton Campaign Considered Targeting FDA's Califf

10/21/2016 02:45 PM |

The Wikileaks disclosure of John Podesta's emails reveals that the Clinton campaign considered attacking FDA Commissioner Robert Califf for ties to drug companies as part of a broader effort to divert attention from Secretary Clinton's email scandal.


FDA Commissioner and Clinton Campaign Target Robert Califf, MD


It start with an email from long-time Clinton adviser Mandy Grunwald to Clinton policy adviser Ann O Leary.  The email contains a link to a NY Times article on acting FDA Commissioner Rob Califf who had been nominated by President Obama to become the full time commish.  

On Sep 21, 2015, at 10:33 PM, Mandy Grunwald sent an email to Clintion policy advierse Jake Sullivan and Ann O'Leary,  Joel Benenson a strategist and pollster for the presidential campaign., press secretary Brian Fallon and Communications Director Jennifer Palmieri and asks: Do we want to weigh in on this?

Jake Sullivan responds:   What do you think?

On Mon, Sep 21, 2015 Mandy Grunwald replies: I don't know anything about the guy. If we weren't hitting the Administration with Keystone this week, I might be tempted, but I think that probably makes it a bad idea. Lets keep an eye on it and see about those Pharma ties. 

Then Anne O Leary:  Interesting. I'll do some asking around to see what folks in the public health world think.

On Sat, Sep 26, 2015 at 12:53 PM, Brian Fallon :  Any update on this? As we consider fights that fit into the larger themes we are trying to promote, this seems like a good fight to have. Plus, the VP would be in a box of having to support this nominee.

On Sat, Sep 26, 2015 at 12:59 PM, Jake Sullivan wrote: This is ultimately a political call, not a policy call. I don't really like the idea of bashing this White House's nominees, knowing their vetting process and standards.  But if you guys want to do it, I cannot identify a policy reason not to -- you all know the facts. Ann, any other intel?

On September 26, 2015 at 1:13 pm  Anne O'Leary wrote:

Califf the Obama nominee does have real ties to the drug industry - Chris Jennings is calling a few people for me to learn more so we don't tip our hand directly. We are clean on Clinton Admin FDA Commissioner - it was David Kessler, an academic who had run a teaching hospital - and best known for taking on big tobacco. We could certainly signal that we want someone willing to stand up to Pharma (in the same way Kessler stood up to Tobacco). BUT - I want to do a little more digging and due diligence before we hit this guy. Having been through a nomination fight with my husband (in which he lost), this is personal and messy and horrible on the person nominated and their families - so I don't take attacking this guy lightly. Do you want to do it on Meet the Press? 

That was follwed by an email from Podesta on Sep 26, 2015, at 2:27 PM,  who wrote: " I think we will pay a huge price with the WH on this one. Worries me."

Nothing transpired.   But the back and forth about whether to trash Califf came down to politics, not policy differences.  And it had NOTHING to do with Califf as a person, a physician, a researcher and public servant.  It was clear that Team Clinton was interested only in dirt that was newsworthy.  It was simply a matter of whether attacking Califf on Meet The Press would be worth the headache of taking on an Obama nominee.   How lovely. 

Rob Califf should remain FDA commissioner regardless of who is elected president because of his qualifications and commitment to accelerating access to safe and effective medicines.   I am concerned that the Clinton team -- which exults about going to war against Pharma -- will seek to replace Dr. Califf.  That will trigger a prolonged political war that will undermine the FDA.    

The emails reveal a Team Clinton eager to find ways to smash up people for short term political gain without tipping their hand that they are behind the hit job.   Like it's war on pharma, it has less to do with policies and more to do about the benefits of creating and attacking enemies. 


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​Limiting co-pay assistance is against medicine’s tradition of benevolence

10/14/2016 04:43 PM |

Written by Rafael Fonseca MD and Robert Goldberg PhD

Two recent articles in the NEJM (1) e) and Annals of Internal Medicine (2) propose that restrictions or eliminations of co-pay assistance programs by pharmaceutical companies are needed since they distort the market and therefore, while few benefit, many suffer in the form of higher healthcare expenditures. They are factually correct but the conclusions point to a larger problem; the third party payer system in health care. When consumers (in this case patients) are detached from the price consequence of transactions they will be less careful in their selections. However, the proposal presented in these articles are, at least in the short-term, patient unfriendly and immediate implementation of their recommendations would limit, severely, access; particularly for patients with serious or life-threatening conditions. The Annals article is notorious in that it fails to mention the increased cost-sharing pressure that patients are facing from the payers.

So what are the solutions?  Ideally, healthcare should be divided between the routine care and the catastrophic care.  Routine care should involve much more “skin in the game.”  In my view, regular care should not be covered under traditional heath insurance but be bought directly, with compassionate support tools for those in need.  In this type of care I could envision more direct pressure in the selection of older medications for which many alternative exist. There are many options for anti-hypertensive medications, statins, etc.  In the absence of a third party payer system the Epipen would never cost $600.  This is where consumer pressure, with co-pay requirement as a discriminator, should be employed; vigorously, if you may.  I would not disagree that if an equivalent generic exists, a true equivalent, then having the patient paying more for a branded product is fine.  This is not to say that branded products and generics are always the same.  Sometimes production quality may suffer or sometimes an alternative may not be the same as the original, similar and yet not the same product.  But if you want the branded statin maybe you should pay a bit more.  Who could argue with that?

However, for more expensive medications, medications used for serious, chronic severe or catastrophic illnesses the pressure seems misguided.  For instance preventing co-pay assistance for patients with cancer seems inhumane.  Dusetzina and colleagues have documented that lack of supplemental insurance delays initiation of treatment for CML (3). Should we disincentivize the use of medications that can be lifesaving for a cancer patient so they consider inferior treatments?  Should we place additional burdens in someone who is at high risk for bankruptcy? Someone who cannot work or whose caregiver cannot work?  That seems inappropriate.  Furthermore, for many of these newer and expensive medications there are no suitable alternatives (4).  Dr. Bach and colleagues were able to reduce the price of a competing monoclonal antibody, but that is a rarity in oncology and more of an exception. Should myeloma patients forgo lenalidomide in favor or thalidomide and face certain peripheral neuropathy?  Or should a diabetic myeloma patient be forced to be treated with bortezomib instead of carfilzomib and again face neuropathy? To create a disincentive as this for people facing serious medical illness appears to me as a fundamental violation of medicine’s stance of benevolence. Rather this has the appeal of altruism, sacrifice the few for the benefit of the many.

Lastly, government regulations that eliminate this co-pay assistance are demonstrably patient unfriendly. Commercially insured patients can receive this directly and in another study by Dusetzina she shows that the average co-pay for specialty medications is only $35 (5). In another study it was shown that 90% of myeloma patients pay less than $100 per month for lenalidomide, a backbone for the treatment of this disease. In the meantime, Medicare beneficiaries struggle to find indirect support with funds provided by the pharmaceutical companies to third parties. I’ve written about this topic before, but again is a built-in disincentive to lessen the use of medications (6).  What if these medications save dollars by preventing hospitalizations and decreasing expenses elsewhere?  Once again it is pound foolish to only concentrate on the price of drugs.

References
1.    Dafny LS, Ody CJ, Schmitt MA. Undermining Value-Based Purchasing - Lessons from the Pharmaceutical Industry. The New England journal of medicine. 2016. Epub 2016/10/13. doi: 10.1056/NEJMp1607378. PubMed PMID: 27732125.
2.    Ubel PA, Bach PB. Copay Assistance for Expensive Drugs: A Helping Hand That Raises Costs. Annals of internal medicine. 2016. Epub 2016/10/11. doi: 10.7326/M16-1334. PubMed PMID: 27723893.
3.    Winn A, Keating N, Dusetzina S. Factors Associated With Tyrosine Kinase Inhibitor Initiation and Adherence Among Medicare Beneficiaries With Chronic Myeloid Leukemia. Journal of Clinical Oncology. 2016;10.1200/JCO.2016.67.4184.
4.    Fonseca R. 2016. Available from: https://tmblr.co/Z0_1wo2CgPnw1.
5.    Dusetzina SB. Share Of Specialty Drugs In Commercial Plans Nearly Quadrupled, 2003-14. Health Aff (Millwood). 2016;35(7):1241-6. Epub 2016/07/08. doi: 10.1377/hlthaff.2015.1657. PubMed PMID: 27385240.
6.    Fonseca R. 2016. Available from: https://tmblr.co/Z0_1wo2D7lHbj.
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