Latest Drugwonks' Blog

GAO Asked to Assess Viability of FDA’s Complex Generics Pathway

The House Energy & Commerce Committee is calling on the GAO to evaluate whether the FDA’s regulatory pathway for generic versions of complex drugs is sufficient.

Specifically, the committee sent a letter Dec. 10 asking the GAO to assess whether generic versions of nonbiologic complex drugs that are not fully characterized present challenges in meeting generic approval standards.

If the agency concludes that meeting approval standards presents challenges, then the GAO should consult with public and private groups to analyze the following questions:

  • What requirements should be established regarding the comparability of the manufacturing process?
  • What degree of characterization of the proposed generic version and the reference product should be required to determine safety and efficacy?
  • What degree of similarity should be required for the active ingredient of the generic version to be deemed the same as the active ingredient in the reference product?
  • What types of evidence should be required to demonstrate bioequivalence?
  • How much clinical evidence is needed?

Once those questions are answered, the agency should determine whether current ANDA pathways can address the use of reference products. The study also should make recommendations for the FDA, such as developing policy documents and establishing general principles on evidence needed.

Read the letter here:

Peter and I just published an article in The Journal of Commercial Biology on how the ASCO Value Framework could hurt patients and stifle innovation
Compare the approach ASCO takes to the one shaping the Cancer Moonshot 2020 effort. 

A new coalition of biotech companies, insurers, patients, regulators was established with the goal of nothing less than using precision medicine to 'cure' cancer.  (A cure meaning controlling and preventing the progression of tumors so that the disease is within us but can not hurt us) 

Today "leaders from large pharma including Celgene and Amgen, biotech including NantWorks, NantKwest, Etubics, Altor Bioscience, and Precision Biologics, major academic cancer centers and community oncologists announced the launch of ‎The National Immunotherapy Coalition (NIC), a historic alliance--in collaboration with Independence Blue Cross, one of the nation’s largest payers and Bank of America, one of the largest self-insured companies in the U.S.--with a singular focus: accelerating the potential of combination immunotherapies as the next generation standard of care in patients with cancer."

This is perhaps the most important scientific initiative undertaken in human history for reasons I will elaborate in another post.  

For now, here are the three most important features of this initiative:

1.  The QUILT (QUantitative Integrative Lifelong Trial) program is designed to harness and orchestrate all the elements of the immune system (including dendritic cell, T cell and NK cell therapies) by testing novel combinations of vaccines, cell-based immunotherapy, metronomic chemotherapy, low dose radiotherapy and immunomodulators -- including check point inhibitors-- in patients who have undergone next generation whole genome, transcriptome and quantitative proteomic analysis, with the goal of achieving durable, long-lasting remission for patients with cancer.

2.   Multiple randomized Phase 2 trials testing genomically and proteomically informed novel combinations of immunotherapy agents, will pave the way to identifying cancer therapy combinations with the lowest toxicity and the highest quality of life.

3.  Insurers will be covering whole genome transcriptomic tests in patients receiving immunotherapy.    Independence Blue Cross is the first health plan to cover next generation sequencing.   The coalition is talking to others, who I think will have to follow.  

This is good for patients and innovation.  And this approach -- which should be replicated for other illnesses where combinations of treatments - old, new and emerging -- will be gold standard of care. 

That mean groups that seek to measure the value of a single cancer drug based on average response --  like ICER,  the ASCO Value Framework, and Peter Bach's comical Cancer Drug Abacus etc. will become obsolete.  That means Express Scripts effort to use the aforementioned comical Cancer Drug Abacus to establish indication based pricing should be discarded and ignored.  Any entity claiming it wants to establish value that does not seek to promote payment and access to precision medicine to match patients to treatments that control and prevent disease most effectively should be considered outdated and obstructionist.  

This is a great day for those committed to cures.  And that should include everybody.  

The death of the transformative musician, artist and filmaker David Bowie to due to cancer underscores once again the value of innovation.


Bowie battled cancer long enough to complete and release his last album on his 69th birthday.  You don't have to be a David Bowie to know that using the retail cost of a cancer drug to discourage it's use would sideline many people with a cancer diagnosis.

As Bowie noted: You can neither win nor lose if you don't run the race. 

As we move ahead in the US with more biosimilars being submitted for approval – and for interchangeability – attention must be paid to patient outcomes.

Case in point is research presented at the 2013 ACR/ARHP Annual Meeting that hasn’t as yet received the attention it deserves:

Efficacy and Safety of CT-P13 (Infliximab Biosimilar) over Two Years in Patients with Ankylosing Spondylitis: Comparison Between Continuing with CT-P13 and Switching from Infliximab to CT-P13

Background/Purpose: CT-P13 is an infliximab (INX) biosimilar recently approved by the European Medicine Agency. PLANETAS was a 54-week (wk) randomized double-blind parallel group multicenter Phase I study demonstrating pharmacokinetic equivalence of CT-P13 (5 mg/kg infusion every 8 wks) with INX, in patients (pts) with ankylosing spondylitis (AS) (Park W, ARD 2013;72(S3):516). Here we report results from the extension phase of the Phase I equivalence study, investigating long-term efficacy and safety of extended CT-P13 therapy and switching from INX to CT-P13 in pts with AS.


In this open-label extension study, a total of 174/210 pts who completed PLANETAS entered into the extension phase: 88 were continuously treated with CT-P13 (maintenance group) and 86 were switched from INX to CT-P13 (switch group) for 1 additional year.

Results: At wk 54 ASAS20/ASAS40 and ASAS partial remission rates were similar between groups (CT-P13, 70.5%/58.0% and 20.5%; INX, 75.6%/53.5% and 19.8%, respectively). During the extension, ASAS20/ASAS40 rates were similar in the maintenance group (70.1%/57.5% at wk 78 and 80.7%/63.9% at wk 102) and the switch group (77.1%/51.8% at wk 78 and 76.9%/61.5% at wk 102). ASAS partial remission rates were also similar between groups; 21.8% and 21.7% at wk 78, and 27.7% and 28.2% at wk 102, respectively. An overview of the efficacy data are shown in the Table. Anti-drug antibodies (ADA) were comparable between the two groups and positivity was maintained throughout the study (maintenance group, 22.2%, 24.4% and 25.0%; switch group, 26.2%, 31.3% and 30.7%, at wk 54, 78 and 102, respectively). ADA negative pts achieved higher ASAS40 responses (maintenance group, 62.9%/61.5%/66.1%; switch group, 58.1%/60.0%/71.2% at wks 54, 78 and 102, respectively) compared with ADA-positive pts (maintenance group, 38.9%/36.8%/55.0%; switch group, 41.7%/33.3%/45.8% at wks 54, 78 and 102, respectively) with no differences between the maintenance and switch groups. The proportion of pts with ≥1 treatment-emergent adverse event (TEAE) was lower in the maintenance group (48.9%) compared with switch group (71.4%) mainly due to fewer mild and moderate AEs. Serious TEAEs were identical between groups (4 vs 4 pts). Other tolerability and safety outcomes were similar in both groups (Table). TEAEs due to hypersensitivity and infusion-related reactions were similar in both groups (5 pts in maintenance group vs 2 pts in switch group). There was 1 case of TB in each group and 1 report of prostate cancer in the maintenance group (considered unrelated to treatment).

The efficacy data was good. But the safety data is concerning:

Safety outcome


CT-P13 throughout study (N=90)

Switched from INX to CT-P13 in extension phase (N=84)

TEAEs, n




pts with ≥1 TEAE, n (%)


44 (48.9)

60 (71.4)



20 (22.2)

27 (32.1)



21 (23.3)

28 (33.3)



3 (3.3)

5 (6.0)

pts with ≥1 TESAE, n (%)


4 (4.4)

4 (4.8)

pts with ≥1 infection, n (%)


23 (25.6)

29 (34.5)

ADA positive, n (%)

Wk 54

20 (22.2)

22 (26.2)


Wk 78

21 (24.4)

25 (31.3)


Wk 102

21 (25.0)

23 (30.7)


ADA, anti-drug antibodies; ASAS, Assessment of SpondyloArthritis international Society; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score C-reactive protein; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event


Biosimilarity and measurement of efficacy is only one dimension. Attention must be paid to effectiveness relative to real-world patient outcomes data. And that means a much closer pharmacovigilance examination of adverse events for both naïve and switched patients.

I received some puzzled responses WSJ's Joseph Walker and Jonathan Rockoff to a couple of tweets I posted regarding the extent to which WSJ articles on drug costs and prices seek to reinforce a narrative by leaving key contextual facts out of said news items.

I recently referred to a WSJ article on advances in myeloma drugs by tweeting: Will @joewalkerWSJ @JeanneWhalen @jonathanrockoff  ignore PBMs, insurers pocket rebates, make patients pay $1000s  Meaning will these reporters follow up with an article on myeloma treatments hat pins the blame on out of pocket drug costs on drug companies as opposed to or in combination with many other decisions undertaken by PBMs and insurers?  Will they look at the impact of such medicines in reducing hospitalizations, infusions, etc that insurers pay for and are more expensive than the drugs patients must partially cover?

Below is a chart that has a link to a specific article on drug costs by each WSJ reporter and whether or not the articles discuss specific issues that would put the cost and value of drugs in context. 

Maybe this will clear up the confusion.  

The Biotechnology Industry Organization changed its name to the Biotechnology Innovation Organization. The group will continue using the "BIO" acronym.

This is more than just cosmetic. It demonstrates the urgency in both promoting and protecting sustainable innovation in biotechnology. If we are going to argue “value” rather than just “price,” than innovation the most important part of the conversation.

We do what we must, and call it by the best names.

Ralph Waldo Emerson

CDC's Opioid Reset

  • 01.05.2016

CDC sees the light …

This morning the CDC will ask the National Center for Injury Prevention and Control's Board of Scientific Counselors to appoint a new work group to review the agency's draft guideline for prescribing opioids for chronic pain. It's the next step in CDC's effort to address complaints over the secretive way in which the initial draft was developed. Public comments on the draft guideline are due Jan. 13, and the new group will be tasked with reviewing those, too.

Spotlight is a movie about how the Boston Globe's investigative team (called Spotlight) exposed the Boston Diocesan's complicity in protecting child molesters in the priesthood.  The most dramatic moment in the film comes when Spotlight's chief, Walter Robinson (played by Michael Keaton) confesses that he buried a story about multiple priests abusing young boys in the in 1970s.  At the time, pursuing the story -- compared to easier and less controversial investigations of police corruption,  racial discrimination,  government incompetency -- went against the ethos of Boston and the narrative that the Church was an integral part of Boston, where most of the reporters were raised.  

While nowhere near the level of irresponsibiity, the WSJ coverage about drug costs appears to be shaped by the same set of beliefs and emotions.  Every article that the WSJ has written about drug costs in 2015 (with the exception of a blog written by Ed Silverman when Pharmalot was part of the WSJ) ignored the role of pharmacy benefit managers and health insurers in hiking the cost of new drugs used by the most chronically ill patients.  The have ignored the fact that PBMs, in particular, pocket 90 billion in rebates, none of which goes to reducing the cost of drugs.  They have ignored the fact that the discounted drugs are less than 3 percent of total health plan spending or that as the percent increases, the cost of other services decline.  They have ignored the fact that health plans have increasd the number of new targeted medicines -- drugs that work best in specific patients -- by 40 percent since 2014.  (See below.)

There are more oversights as well but the list above suggests that the WSJ -- including the most recent WSJ article -- has a blind spot, not a spotlight on the issue of drug costs.  The WSJ is burying the real story to sustain a narrative, at the expense of patient well-being. 

Our focus in 2016 will be to create greater transparency about how drug prices are set and by who, how those decisions affect patient access to and affordability of such medicines, what affect access has on patient well-being, mortality and health costs and finally, what changes in decisionmaking can reduce spending and increase value (to patients) long term.  

Further,  we will look at how the reactionary defense of the randomized clinical trial is the greatest rate limiting factor in reducing the time and cost of bringing new  medicines, diagnostics and devices to patients.   This will NOT be an FDA pinata festival.   Rather, the RCT is being protected by leading medical journals, academic research centers, major medical specialty societies and health insurers.   
Pessimism sells.  As Ben Wattenberg, the late political observer wryly noted: “Worse is better” if you are looking for headlines, grants, attention and want to be deemed an expert.  (Self help gurus being the exceptions.) 

Pessimism is necessary in small doses, allowing us to anticipate, adapt to and often avoid failure or danger.   It is also an adjuvant for change. (I don’t know what that means but it’s pithy enough to sound smart.)  But apocalyptic pessimism, the pessimism that uses every event or fact to confirm certain doom unless we change our ways, is corrosive and unreliable.  How do we know?

As Matt Ridley, another professional optimist observes. “For 200 years pessimists have had all the headlines, even though optimists have far more often been right.”

The steam powered train was predicted to bring ruin to England.
The industrial revolution was supposed to bring enduring misery to millions.
The poor will always be poor.
The sky is falling; the ice caps are melting.
We will run out of oil and natural gas.
Drug prices are unsustainable.

If we had followed the pessimists prescriptions (government control or manipulation of wealth, natural resources, population levels and prices) the world would be more like North Korea than North Dakota. 

I will focus on the last perennial pessimistic prediction. 

We heard and read a lot about drug prices being out of control, skyrocketing, unconscionable, etc. 

In every era where new medicines emerge, the same claim is made.   Te same bunch of pessimists trot out the same proposals: government price controls and rationing.  (Now repackaged as various value frameworks.)

And each time the apocalyptic predictions that new medicines would be unaffordable or would add nothing to our lives  or drive up the cost of health care were wrong. 

2015 was all about drug pricing because there were so many new and expensive (relative to most consumer purchases) medicines hitting the market.   But in fact the high prices – and indeed even the anger about drug prices – are a healthy sign of progress.

It means that diseases that were fatal can be cured for controlled, including Hep C, many cancers and Ebola.  It means that more diagnostics are being developed to match people to the right combination of treatments and to monitor health in real time.  It means that more investment in new treatments for smaller groups of people will be developed.  Nothing sends a signal about the demand for better medicines than high prices. 

At the same time, the high prices are forcing drug companies to do something the rest of the health care system will have to do: change business and financial models to make the case for value and increase the pressure to abandon outdated clinical development tools (randomized clinical trials) and find other ways to demonstrate the health benefits of their goods and services.

Prediction is over-rated when it is too precise.  But the general trend of medical innovation, the digitization of biology, is part of a broader evolution in how we create and use the things that give us joy, insight and well-being.  Our world is better because the footprint for change is getting smaller and faster.  In a WSJ op-ed Andy Kessler wrote that “on Dec. 29, 1959, the physicist Richard Feynman delivered a famous speech at the California Institute of Technology titled “There is Plenty of Room at the Bottom.” He predicted almost limitless possibilities if we could “manipulate and control things on a small scale.” He nailed the next five decades of ever-shrinking realms that ultimately produced trillion-dollar markets in microelectronics, nanotechnology and bioengineering through DNA-level manipulation.…The smaller technology shrinks, the bigger the world can grow. Smaller transistors, faster processors, cheaper sensors will all allow innovators to tackle problems with tremendous precision. It’s as if, because there is plenty of room at the bottom, now there is plenty of room at the top.”

We are increasingly able to navigate and understand what Lee Hood calls “the dark matter of human biology.”  New medicines are the result of our ability to explore health, wellness and disease at a molecular level. 

Here’s a non-pessimistic prediction: the next trillion-dollar market will be new treatments and algorithms that control disease and keep people healthy.   You have to try really hard to despair about that!

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.

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