Latest Drugwonks' Blog

I've just returned from Singapore where I spent some quality time with Raymond Chua (the director of the Singapore HSA -- their version of the FDA) and his senior staff. We covered a wide variety of issues ranging from "what's new at the USFDA?" (Answer -- a lot!), global regulatory convergence, and much in between (such as Singapore as a regulatory “third way” in addition to the FDA and EMA).

The HSA directorate was particularly interested to discuss the USFDA's expedited review pathways (breakthrough therapy designation, accelerated approval, priority review, etc.) and some of the ways they’re impacting regulatory policy (i.e., adaptive clinical trial design, senior staff commitment, earlier sponsor/agency interaction). Per Raymond, the HSA is "pathway agnostic" -- an interesting concept that deserves more discussion and consideration in White Oak. He was also keen to learn more about the USFDA's new "Super Office" of Pharmaceutical Quality. (For more on this, see here.)

When it comes to 21st century drug and device regulation, Singapore is a place to study for best practices as well as innovation in both cogitation and action.

The Merlion roars loudly and proudly on behalf of it’s nation’s public health. And there's much the rest of the world can learn from both it's practices and world view.

(And the eats are pretty spectacular too. I recommend the Chili Crab.)

In his NYT oped "The Solution to Drug Prices" Zeke Emanuel claims price controls are a good thing as long as they are connected to the value of the drug.  I assume that he thinks longer life and reduced health care spending are measures of value. 

He thinks Australia and Switzerland are good examples of how to do price controls right. 

In fact, there are several studies of both pricing systems.  In Australia life expectancy increased by 11 months for people who had access to new drugs faster.  mean age at death increased more for diseases with larger increases in mean drug vintage.  Life expectancy for people who had older medicines didn't budge.In  Australia’s Pharmaceutical Benefits Advisory Committee recommended only  two of twenty-six drugs  with a cost per life-year saved greater than $57,000. Only one of twenty-six submissions with a cost per life-year saved less than $32,000 was rejected. Australia ranked 18th out of 20 comparable OECD countries in access to new medicines, with cancer patients waiting over two years after a drug is approved

In Switzerland a study concluded that 17000 life years were gained in 2012 due to the kind of cancer drugs Emanuel claims are NOT cost-effective.  In fact the cost per life-year before age 75 gained from cancer drugs was $21228.  Moreover, the study found that by delaying access to these medicines as part of the price control program, Swiss cancer patients died sooner than they had to.  Finally, another study concluded that Swiss heart patients  who  used  newer  cardiovascular  drugs  in 2003 lived longer than  people  who used older cardiovascular drugs. (Meanwhile, in the US generic versions of patent medicines are less expensve than the price controlled brand products in Europe.)

Americans with heart disease and cancer live longer than patients in other countries even though many spend more on on these diseases.  The price controls Emanuel pushes would save less than .5 percent of total US health spending.  They would drive up total costs and make life shorter and more painful for millions.


First there was Orphan Medical (Caronia), then Amarin. Now Pacira Pharmaceuticals has filed a lawsuit against FDA seeking declaratory judgment that the agency may not prohibit them from providing "truthful and non-misleading" information about the use of Exparel bupivacaine. 

Pacira is seeking preliminary and permanent injunctions to prevent FDA from taking action against them on the basis of proposed "truthful and non-misleading" speech. The suit was filed in the U.S. District Court for the Southern District of New York. 

FDA approved Exparel in 2011 for postoperative pain management. 
In September 2014, FDA sent Pacira a warning letter asking the company to stop promoting it for use in surgical procedures other than bunionectomies or hemorrhoidectomies. The agency letter also disputed Pacira's claim that Exparel provides pain control "that lasts for up to 72 hours" as an overstatement of efficacy that was "false and misleading."

Pacira argues that, even if the indications it promoted were considered off-label, they still have the right to promote "truthful and non-misleading" information about the drug under the First Amendment and cited the recent district court opinion allowing Amarin to engage in "truthful and non-misleading speech" to promote off-label use of Vascepa.

What do the Caronia, Vascepa, and Pacria cases have in common? Well, for one thing all the plaintiffs are small companies, largely dependent on the sales of a single product for their revenues. Suing the FDA used to be considered a high-stakes gamble, but recent rulings – and the lack of action on the part of the agency to put forward new draft guidance – seem to have changed the risk/benefit analysis. At least for small companies.

(And the odds-makers of Wall Street think so too. 
Pacira gained $2.71 to $60.18 on Wednesday.)

Can lawsuits by Big Pharma be far behind?

As far as anything from White Oak … Car 54 where are you?

Well Kyle Bass does have some people in his corner.   It's Don Seiffert of the Boston Business Journal who says: "The fact that he (Bass) also planned to profit off the scheme by selling short the companies he planned to target, he has said, is incidental to his real goal of knocking down inflated drug prices."

When did taking a hedge fund manager at his word become the hallmark of business journalism??

How about if reporters wrote that "the fact that the Ayatollah also planned to use funds to finance terror, he has said,  is incidental to the real of achieving world peace."

As for objectivity, Seifert has been a critic of drug prices over the years, claiming that "The free market approach is no longer working to ensure price competitiveness through generic drugs."

That leaves either price controls, which Seifert supports or Kyle Bass wiping out biotech valuations by using a factless assault on the patents of such company.

I can see how price contols would reduce prices.  But how exactly does shorting biotech stocks reduce drug prices?   Why not challenge patents directly under Hatch-Waxman?   

Because the alternative process is, in the right hands, a process that rewards extortion.  

The Inter Party Review was designed by Congress to make it easier for a handful of tech companies to swat away frivilous challenges to their patents.  Instead, rather than fulfilling its original intent of weeding out weak patents, IPR’s and the Patent Trial and Appeals Board (PTAB) have become “patent death squads” as they strike down 77% of the patent claims under review.   The IPR process is being used to undermine confidence in the patent system. A recent article estimates the resulting cost to the U.S. economy as over $1 trillion."

As Peter noted in a recent WSJ op-ed Kyle Bass is leading the way in destroying confidence in patents.  As Barron's observed (Seiffert might want to tape this article on the wall above his computer to remind himself of what good reporting is) Bass teamed up with Erich Spangenberg, CEO of IPNav, to challenge what they argue are questionable patents held by pharmaceutical companies to stifle competition from the generic marketplace. (It’s worth noting that Bass’ new partner, Spangenberg, has been described as the world’s most notorious patent troll. IPNav says it has generated over half a billion dollars in licensing revenue in patent-infringement penalties for its clients, which include individual investors, corporations, and universities.)

Bass's greed (and Peter's article) has led to Congress closing this loophole and the board that does the reviews to tighten up it's requirements.  A while ago, Seffert predicted that the board's rejection of the  Bass attempt to invalidate  Acorda Therapeutics patent for it's drug, Ampyra was just a temporary setback.  

He wrote: "But according to Lana Gladstein, a partner in the Intellectual Property Department at Nutter McClennen & Fish, the ruling was very narrow, and baed on the fact that the supporting evidence Bass submitted was insufficient. It has no bearing on his attempts to knock out patents held by Biogen (Nasdaq: BIIB) for its top-selling drug, Tecfidera, nor by Shire (Nasdaq: SHPG) for its drug for short bowel syndrome, Gattex."  Or I guess his efforts to shake down Celgene or any other companies.  

Too bad for Seiffert, Bass has been 0 for whatever in this extortion racket.

Kyle Bass will soon have to find another way to make up for what might huge losses from his investment in oil stocks (pre-price decline) and GM..  
Perhaps he can take comfort in the fact that one journalist is in his corner and still regards anything -- no matter how sleazy or destructive -- that knocks down drug prices as a victory.  

There's been a lot of sub-textual cheering by The Wall Street Journal about the a court's ruling that Novartis can sell Zarxio, the biosimilar version of Amgen's Neupogen approved by the FDA a few months ago.  In particular, the PBMs have been saying that eventually as more biosimilars hit the market , the discounts to payors and PBMs will be 40-50 percent.  

Previously, the WSJ stated the approval was akin to " firing the starting gun on a new industry" that will reign in drug spending. 

More like shooting blanks.   

First, it is important to remember, as the FDA noted in it's approval, that " ZARXIO has not been determined to be interchangeable."  Which means: No switching. 

Second, a biosimilar requires a Phase III trial.   Prior to obtaining approval, Novartis-Sandoz had to conduct the PIONEER study (the official title is A Randomized, Double-blind, Parallel-group, Multi-center Phase III Study Comparing the Efficacy and Safety of EP2006 and Neupogen® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy)  The trial was initiated in 2011 and the results of the study were submitted in 2014.    Several studies estimate it takes 8-10 years and anywhere from $100 million to $250 million to produce one biosimilar. (That does not include the capital costs of failure, delay, etc. )  That timeline is no different than innovative drugs.  That fact should squash the conspiracy theorists like Public Citizen or Donald Light and Hagop Kantarjian who claim that's what a new biotech costs to develop since a biosimilar takes NO risk in investing in preclinical and early human studies. 

Third,  biosimilars will require the same post market surveillance expected of innovator products.  My colleague Peter Pitts has articulated the need for this -- and for monitoring marketing claims -- better than anyone.  

For these reasons, biosimilars have not been a profitable business.  That will change as more biotech products go off patent.  But don't expect deep discounts as long as the costs of development increase.  

Instead, it is possible that companies producing biosimilars will seek to increase profit margins by developing therapies that add value.  Turning an injectible into an oral treatment is one way.  Reformulations and drug combinations are others.  Companies will likely seek to create niches using diagnostics and finding additional uses for products. 

Which raises the possiblity of authorized generic versions.   Or not.   My guess is that Amgen will compete on price and seek additional indications for Neupogen.  
Biosimilars will not save the gazillions estimated by the media.    Rather, they will promote the kind of competition one sees in smartphones and tablets: similar functions, different consumer experiences as a result of incremental, but useful, changes in technology. 

That's innovation.  And that's good for patients. 

My article from the Louisville Courier-Journal on the ASCO Value Framework.  It can also be read as an analysis of Dr. Daniel Goldstein's effort to measure the value of a new medicine for people with stage IV squamous, non small cell lung cancer...

A group of cancer doctors has apparently decided to rewrite the Hippocratic Oath.

The ancient pledge charges physicians with applying “all measures that are required” for the benefit of the sick. The docs heading up the American Society of Clinical Oncology want to add a caveat — “unless those measures are too expensive. Then just let the patient die.”

The oncologists’ group has developed a “conceptual framework” that relies on cost-benefit analysis to determine the most “valuable” treatments for different patients.

Sounds innocent enough. But healthcare outcomes cannot be reduced to cost-benefit calculations. By focusing on the cost of a treatment — rather than the benefit it could deliver — the oncologists are allowing dollar signs to dictate whether a patient lives or dies.

Under ASCO’s framework, new treatments will be judged “based on clinical benefit, side effects and cost.” Those are the exact same measures health insurance companies use in limiting patient access to treatments. Indeed ASCO wants insurers to use its calculator to “evaluate the relative value of new treatments” as they develop “benefit structures, adjustment of insurance premiums, and implementation of clinical pathways and administrative controls.”

Such “controls” could include shifting drugs to the highest cost-sharing tier of an insurance plan or requiring patients to try older, cheaper drugs before gaining access to the most cutting-edge therapies.

Never mind that the Obama Administration has warned “placing most or all drugs that treat a specific condition on the highest cost tiers discourages enrollment by individuals based on age or based on health conditions” is discriminatory.

The oncologists are effectively asking insurers to discriminate against cancer patients — in direct contradiction of the Affordable Care Act’s intent.

ASCO’s framework openly ignores what really matters — benefit to patients.

Consider how the framework attempts to dictate how long a person “should” live. It claims that patients “overestimate the benefits of treatments that sometimes extend life by only weeks or months.”

In other words, ASCO has concluded that a treatment that can keep patients alive for weeks or months has no real value.

The framework assigns zero value to any treatment that doesn’t increase survival by 20 percent. Right off the bat, numerous treatments for pancreatic, brain, lung, and stomach cancer today would be deemed worthless by the formula.

That 20 percent figure is completely arbitrary. Consider the case of someone with lung cancer who is alive today because of the accumulation of treatments that never made that arbitrary threshold. Cardiologists hailed a just approved drug that reduces the risk of death from heart failure by 20 percent as revolutionary.

Under ASCO’s framework, sorry — not good enough.

Between 1987 and 2000, various AIDS therapies increased patient life expectancy by less than 20 percent a year. Had ASCO’s framework been in force then, thousands of AIDS patients who benefited from those treatments would not be alive today.

ASCO defends its guidelines by claiming that expensive new treatments have sown “unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.” The American healthcare system can’t afford limitless spending on cancer treatments, the group says.

It’s true that spending on cancer drugs has risen. In 2014, it topped $100 billion. But that figure represents just 1 percent of U.S. healthcare spending.

What’s more, these medicines work — and are worth their price tags.

Successful drug therapies reduce overall medical costs by diminishing the need for future doctor visits and hospital stays. According to a study from the Center for Value and Risk in Health, specialty drugs often cost more than traditional drugs but “also tend to confer greater benefits and hence may still offer reasonable value for money.”

Successful treatment does more than just lower health costs and offer patients priceless extra time with loved ones. It also benefits the nation. According to one study, cancer survivors have contributed $4.7 trillion to the economy since 1990, simply by living and working longer.

Indeed, according to a Health Affairs study, “current technology assessments, which often determine access” to cancer therapies “may be missing an important source of value to patients and should either incorporate hope into the value of therapies.”

By valuing treatments based on what they cost insurance companies rather than the benefit they provide to patients and their families, the ASCO framework violates both the letter and spirit of the Hippocratic Oath. It should be scrapped before it puts patients in danger.

Today, the Critical Path Institute, founded by Ray Woosley, is celebrating it’s ten year anniversary.

Ray and C-Path has done more to advance personalized medicine than most.  C-Path – working closely with pharma and the FDA -- have led the development of tools and markers that are now routinely used in clinical trials to more quickly and accurately developed tools matchpatients to treatments that deliver the most benefit relative to risks.  

When C-Path was first launched it was difficult to bring together patients, researchers, private companies and regulators.  Under Ray’s stewardship and with the quiet but essential support of the FDA (especially Janet Woodcock) the collective intelligence C-Path brought together has been instrumental in transforming the clinical trial landscape around the world

And the best is yet to come: As current C-Path CEO Marsha Brumfield has written: “the boundaries are expanding with the growing realization of the substantial benefit that can result from new discoveries (such as biomarkers, modelling tools and clinical outcome assessments (COAs)). Even clinical data, traditionally considered proprietary, are contributed to pooled databases to help solve prespecified research questions.

The tools and methods created through sharing information precompetitively are changing the landscape of clinical trial design, enabling trials to be more optimally designed and executed. “

Peter and I are proud to have had Ray as a ‘rabbi’ and an ally in promoting personalized medicine.   We look forward to working with him and C-Path in the years ahead.

HRSA's 340B Fix

  • 08.28.2015

HHS's Health Resources and Services Administration (HRSA) has issued draft guidance on the 340B program that addresses some of industry's concerns with the program. Per BioCentury, the guidance includes a clearer definition of 340B-eligible patients.

The 340B program is intended to provide discounted outpatient drugs to hospitals that serve a disproportionate share of poor and uninsured patients. The 340B hospitals can then dispense the discounted drugs to their non-Medicaid outpatients and use the savings to pay for the care of indigent patients.
However, the number of 340B-eligible entities and discounted drugs sold to those entities has grown over the last several years, and industry has said some hospitals are not using the money to pay for charity care and are dispensing the discounted drugs to individuals who are not patients of the hospital.

 In the draft, HRSA clarifies which patients would be eligible for 340B: those who receive care at the hospital and who have received a prescription from a provider directly affiliated with the hospital. The rule notes that a patient would be ineligible if the drug is dispensed while they are still an inpatient; if the only service provided by the hospital or provider is to dispense or infuse the drug to the patient; if the patient's physician has credentials or privileges at the hospital but who is not an employee of the hospital; or if the patient is an employee of the hospital but may get care elsewhere. 

Additionally, if patients of the covered entity choose to have their prescription filled at a pharmacy not affiliated with the hospital, the drug would be ineligible for the discount. 
The guidance also would allow manufacturers to audit covered entities if the manufacturer "has reasonable cause" to believe that the entity is providing duplicate discounts to Medicaid patients or diverting drugs to ineligible patients.

The draft guidance will be published in the Federal Register on Friday. Comments are due October 27th.

On Tuesday OMB completed its review of a proposed rule entitled "Designation of Official Names and Proper Names for Certain Biological Products."

It's as predicted ... and good news.

According to the Wizards of White Oak, “ Our current thinking is that shared nonproprietary names are not appropriate for all biological products. There is a need to clearly identify biological products to improve pharmacovigilance, and, for the purposes of safe use, to clearly differentiate among biological products that have not been determined to be interchangeable. Accordingly, for biological products, we intend to designate a nonproprietary name that includes a suffix composed of four lowercase letters. Each suffix will be incorporated in the nonproprietary name of the product.

This naming convention is applicable to biological products previously licensed and newly licensed under the PHS Act. The nonproprietary name designated for originator biological products, related biological products, and biosimilars will include a unique suffix. However, FDA is considering whether the nonproprietary name for an interchangeable product 2 should include a unique suffix, or should share the same suffix as its reference product. FDA invites comment on the draft guidance and solicits comments on ways to improve active pharmacovigilance systems for the purposes of monitoring the safety of biological products.

 The Proposed Rule says:

"The official names and proper names of these products would include distinguishing suffixes composed of four lowercase letters and would be designated as filgrastim-bflm (BLA 125553), filgrastim-jcwp (BLA 103353), filgrastim-vkzt (BLA 125294), pegfilgrastim-ljfd (BLA 125031), epoetin alfa-cgkn (BLA 103234), and infliximab-hjmt (BLA 103772). Although FDA is continuing to consider the appropriate naming convention for biological products, including how such a convention would be applied retrospectively to currently licensed products, FDA is proposing to take action with respect to these six products because of the need to encourage routine usage of designated suffixes in ordering, prescribing, dispensing, recordkeeping, and pharmacovigilance practices for the biological products subject to this rulemaking, and to avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway."

A win for sanity and patient safety.

Also, if you'd like more on the related biosimilar J-Code issue, see here.

Over at Forbes, the always thoughtful Matt Herper asks, “Remember when the FDA rejected drugs?”

Per Matt, “As recently as 2008, companies filing applications to sell never-before-marketed drugs, which are referred to by the FDA as “new molecular entities,” faced rejection 66% of the time. Yet so far this year the FDA has rejected only three uses for new chemical entities, and approved 25, an approval rate of 89%.”

(These numbers come from a new analysis commissioned by Forbes from BioMedTracker. The way BioMedTracker follows new molecular entities is slightly different from the way the FDA does. BioMedTracker users want to know about every use of a new medicine. That means that the 2015 rejection count includes rejections of Avycaz, a new antibiotic from Allergan, for hospital-acquired pneumonia, and selling Jardiance, a diabetes drug from Eli Lilly and Boehringer Ingelheim , in combination of metformin. But Avycaz was approved for two other uses and Jardiance is on the market by itself.)

Herper, “… it’s worth sticking to BioMedTracker’s definitions, because it allows us to compare this incredibly high approval rate with the past. And that tells a story of an agency that has been giving the green light more and more often.”

Interesting stuff – but what’s missing is a discussion of how the evolution of regulatory science has impacted the dynamic relationship between the FDA and the innovative pharmaceutical industry and has changed over the course of time (by design, and largely through the mechanism of PDUFA negotiations) the quality of NDAs reaching agency review.

More agency/sponsor meetings earlier in the process not only result in better submissions (more likely to be approved because of higher quality science and more sophisticated protocols), but fewer applications of questionable value . As one senior FDA official told me yesterday, “We’re seeing fewer dogs.”  

Another factor that’s important to consider is that failed NDAs are expensive. The following figures are illuminating.

  • A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.
  • Shifting 5% of clinical failures from Phase III to Phase I reduces out-of-pocket costs by $15 to $20 million.
  • Shifting failures from Phase II to Phase I would reduce out-of-pocket costs by $12 to $21 million.
When he was asked why he was so successful, Thomas Edison replied, “Because I fail faster than everyone else.” One of the reasons the FDA is seeing fewer dogs is because they are helping innovators to recognize failure earlier in the process. And that also means more money that can be reinvested in new clinical programs. Furthermore, a high turndown rate is not a badge of honor--it is indicative of a dysfunctional system.

The good news is that more R&D time, talent, and treasure is being focused on personalized medicine using more sophisticated tools (i.e, biomarkers). Failure is being found sooner, targeted clinical success is easier to predict earlier – and can be expedited through the regulatory process through many new and exciting review pathways (i.e., Breakthrough Designation).

(PS/ Those who don’t think the FDA has “adaptive licensing” opportunities don’t understand what’s going on. And those who choose to blame the FDA for biotech investor anxiety had better find some new excuses.)

Those who wave their arms about the FDA “approving everything” don’t see (or choose not to see) the important success story behind the headline. That dog don’t hunt.


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

Blog Roll

Alliance for Patient Access Alternative Health Practice
Better Health
Biotech Blog
CA Medicine man
Cafe Pharma
Campaign for Modern Medicines
Carlat Psychiatry Blog
Clinical Psychology and Psychiatry: A Closer Look
Conservative's Forum
Club For Growth
Diabetes Mine
Disruptive Women
Doctors For Patient Care
Dr. Gov
Drug Channels
DTC Perspectives
Envisioning 2.0
FDA Law Blog
Fierce Pharma
Fresh Air Fund
Furious Seasons
Gel Health News
Hands Off My Health
Health Business Blog
Health Care BS
Health Care for All
Healthy Skepticism
Hooked: Ethics, Medicine, and Pharma
Hugh Hewitt
In the Pipeline
In Vivo
Internet Drug News
Jaz'd Healthcare
Jaz'd Pharmaceutical Industry
Jim Edwards' NRx
Kaus Files
Laffer Health Care Report
Little Green Footballs
Med Buzz
Media Research Center
More than Medicine
National Review
Neuroethics & Law
Nurses For Reform
Nurses For Reform Blog
Opinion Journal
Orange Book
Peter Rost
Pharm Aid
Pharma Blog Review
Pharma Blogsphere
Pharma Marketing Blog
Pharmacology Corner
Pharmaceutical Business Review
Piper Report
Prescription for a Cure
Public Plan Facts
Real Clear Politics
Shark Report
Shearlings Got Plowed
Taking Back America
Terra Sigillata
The Cycle
The Catalyst
The Lonely Conservative
Town Hall
Washington Monthly
World of DTC Marketing
WSJ Health Blog