Latest Drugwonks' Blog

The road to Hell is paved with good intentions -- and often hidden agendas.

Generic drug manufacturers have complained that innovative pharmaceutical manufacturers use FDA-mandated safety-based distribution requirements—called “risk evaluation and mitigation strategies” (REMS)—to prevent or delay generic medicines from coming to market. Some generic and biosimilar manufacturers have argued that innovative manufacturers use REMS to avoid selling samples of their medicines to competitors, which results in some generic and biosimilar manufacturers being unable to complete the testing necessary to obtain FDA approval of their medicines.

To address this issue, generic and biosimilar manufacturers are supporting, the “Creating and Restoring Equal Access to Equivalent Samples Act of 2016” or the “CREATES Act.” The CREATES Act allows a generic or biosimilar manufacturer to bring a civil action in federal court against an innovator to obtain injunctive relief and monetary damages in two instances: (1) where the innovator has failed to provide samples of a drug or biological product within 31 days of a request for samples, and (2) if the companies fail to reach an agreement on the development of a single, shared REMS system. While seeking to address a narrow issue, the bill is drafted in manner that will put patients and medical researchers at risk of serious harm and generate significant and meritless litigation costs for innovative pharmaceutical manufacturers.


The CREATES Act Lacks Adequate Patient Safety Protections

* The CREATES Act fails to adequately protect both patients and medical researchers who participate in clinical trials of REMS drugs conducted by generic or biosimilar manufacturers. This is concerning because REMS drugs are not typical prescription medicines—they are a special class of potentially harmful drugs that may be subject to restrictions called “elements to assure safe use” (ETASU), which FDA deems as necessary to ensure patient safety. In fact, many REMS drugs subject to ETASU may only be distributed with specific safeguards to protect anyone who comes in contact with the medicine.

* The bill fails to ensure sufficient FDA oversight of safety protections for subjects and researchers in studies of drugs having REMS with ETASU. To obtain an authorization, a generic or biosimilar manufacturer may -- but need not -- submit a clinical trial safety protocol outlining its planned testing of the drug in patients. The bill does not require FDA to pre-approve the safety protocol or to even make the determination that it provides equivalent protections for patients and researchers in comparison with the REMS with ETASU. The bill also grants FDA no authority to suspend a generic or biosimilar manufacturer’s access to samples or otherwise modify or revoke an authorization if the generic or biosimilar manufacturer does not implement appropriate safeguards.

* Instead of providing the FDA with authority to address these safety issues, the bill tasks the federal courts with adjudicating the terms. Although the bill contemplates a limited role for FDA in the authorization process for these products, the federal courts will determine what, if any, safety protections imposed on the transfer of samples are reasonable. The federal courts lack the expertise of FDA in evaluating the safety of a medicine and the measures necessary to protect patients and researchers.

The CREATES Act Exposes Innovative Manufacturers to Liability Risks Through No Fault of Their Own

* The CREATES Act will hold innovators responsible for the actions of generic and biosimilar manufacturers because the bill provides innovators liability protection only for claims arising out of failure to follow adequate safeguards during handling or use of product by the generic or biosimilar manufacturer. As a result, innovative manufacturers could still be unfairly liable for others’ negligence, long after the medicine has left their control. The CREATES Act exposes innovators to significant new liability risks based on the actions of their competitors.

The CREATES Act Hurts Patient Access to Life Sustaining Therapies During Drug Shortages

* The CREATES Act could exacerbate drug shortages and further limit the supply of medically necessary drugs. If a medicine has been on the shortage list for more than six months, the medicine is not exempt from the bill. In other words, manufacturers of these products would be forced to divert medicines from their patients—even when the medicines are life sustaining—to ensure supply for their competitors’ clinical trials.

More careful consideration needs to be inserted into the CREATES Act design so that it more clearly addressed its intent and avoids unintended consequences or hidden agendas. Patient safety, public health, and healthcare innovation mustn't become innocent victims.

Besmirching White Oak

  • 06.16.2016
  • Peter Pitts
A very upsetting story about an FDA official who sold information to an investor.

This person should go to jail.

For a long stretch.

For shame.
This post on ICER from a patient's perspective is by Don Wright.  Don is a lawyer living and working in Minnesota and  has been running marathons since 2002.   In 2003 he was diagnosed with multiple myeloma, a blood cancer with no cure.  He went on an experimental treatment that year and is now on the verge of completing his 97th marathon.  Running is a part of fighting back against myeloma, as well as a celebration of life.  He is a leading advocate for cancer patients around the world.   This post argues that a doctor using ICER guidelines to determine treatment access would at the very least violate the Hippocratic Oath.

Who is ICER?

ICER is the Institute for Clinical and Economic Review.  As far as I can tell, it is funded primarily by insurance companies and by nonprofit organizations who, in turn, are funded by insurance companies.  They claim some funding by the federal government as well.  Other members include pharmaceutical companies who apparently participate in order to have some voice in ICER's proceedings.  A quick Google search shows that the title of many of ICER's documents is "Building Trust through Rationing," which I believe is their mantra and suggests their real purpose.

ICER deals in statistics, not medicine, and a primary goal is to control costs.  I assume that this is why they don't want participation by patients.  They have been working on a report for multiple myeloma, and we myelomiacs have been concerned that they would produce a one-size-fits-all treatment algorithm that doctors might be expected to follow and insurers might try to enforce.

Garbage In, Garbage Out

ICER issued their final report on Myeloma on June 9, 2016, attempting to grade different myeloma treatments to provide comparative medical and cost values.  In my opinion this report is ridiculous on its face, saved only by one of its final recommendations.  ICER claims to have found over a thousand potentially relevant literature references to myeloma treatment, considered 38 worth reading, and exactly six Phase III studies worth analyzing to form their conclusions.

Thus they chose to ignore all Phase I and Phase II studies, which provide by far the largest part (I'd guess 90%?) of the current, up-to-date information that the FDA uses for drug myeloma approval and that doctors actually use in their day-to-day care of myeloma patients.  For this reason, ICER's entire analysis is fatally flawed.  As we say in the computer industry: "Garbage in, garbage out."


As just one example of this blinders approach, the report ignores an old but widely-used myeloma treatment called cyclophosphamide (Cytoxan), which is frequently combined with dexamethasone (DEX) and either bortezomib (Velcade) or lenalidomide (Revlimid).  Indeed, many patients will recognize cyclophosphamide with bortezomib and DEX as the CyBorD regimen.  Because cyclophosphamide is relatively low in cost, it certainly should have been included in any economic analysis, but it appears nowhere except peripherally in the addenda. 

ICER's peculiarly superficial analysis also minimizes or omits many other commonly-used and highly-effective regimens.  Worst of all, it gives especially poor grades to the treatments that are newest and possibly the most effective, such as pomalidomide (Pomalyst) and daratumumab (Darzalex).

Saved by the disclaimer:

One recommendation near the bottom of the final report and in the shorter Report-at-a-Glance, saves the report from total disrepute.  This appears under the heading "Insurers:"
Multiple myeloma is a condition in which many patients will cycle through most or all available treatments, and there is substantial variation in drug mechanisms of action and in the personal patient values that guide consideration of the trade-offs between extended survival and different side effect profiles. Given this background, and in the absence of better evidence, payers should not consider step therapy or “fail first” coverage policies for myeloma treatments.Amen.  This statement seems to have two important implications:
ICER recognizes that their report has no value in guiding treatment for any particular patient (i.e. it turns out that we wasted our time producing this report); and
The PATIENT (the payer) is responsible for choosing an insurer or a plan which does not demand step therapy or "fail-first."Let that be a lesson to us patients!  Maybe the best advice I've seen today - if you have a choice of insurers, choose very carefully.

My bottom line opinions:
A doctor attempting to use the results of this ICER report as the primary guide for treating a patient would be committing medical malpractice, and if so
It follows that an insurance company or plan that denied coverage based upon this report would be demonstrating a singular contempt for their own client, the policyholder.  
According to a letter to the FDA from the GPhA and its Biosimilars Council:

“… we are concerned about the FDA’s requirement to include a biosimilarity statement on biosimilar labeling. The biosimilarity statement is at best unnecessary. The FDA has never required any similar statement for products found to be therapeutically equivalent, and has not provided sufficient justification for its inclusion in biosimilar labeling. Moreover, the biosimilarity statement will be confusing to patients and providers who are unfamiliar with this type of unprecedented statement. This confusion could put biosimilar utilization, and savings, at risk.”

Not so.

Consider generic drugs and information transparency. According to the FTC’s 1979 report on generic drug substitution, that agency concluded, “increased communication (as well as lower prices) may explain why most pharmacists report that product selection laws have had a positive effect on their relations with patients”

Safety and trust are exactly why transparency-in-labeling is needed. As Sumant Ramachandra, Senior Vice President & Chief Scientific Officer at Pfizer’s Hospira unit, has said, “Communications fosters confidence.”

And Geoffrey Eich (Executive Director, R&D Policy, Amgen) has asked:

Why not transparently label biosimilars to engender patient and physician confidence?

Why not ensure accurate patient medical records that clearly identify specific products?

Indeed, at a time when the FDA is considering a rule for the differential labeling of small molecule generics, why not transparency in biosimilar labeling?

It’s important to mention that the majority of the letter signatories are … payers.

Draw your own conclusions.
What Does Future Hold After Woman Infected With Drug-Resistant Superbug?

By  Kathy Ritchie

Updated: Friday, June 10, 2016 -- For the first time, a person in the U.S. has been infected with bacteria resistant to an antibiotic used as a last resort. The woman, who is from Pennsylvania, is recovering after it was discovered she was carrying a strain of E. coli resistant to the antibiotic colistin. But public officials say this should serve as a wake-up call for everyone.

It’s something many of us take for granted— the ability to go to our doctor and get an antibiotic for something as common as a urinary tract infection. But what to do when antibiotics stop being effective?

Colistin is the antibiotic of last resort for particularly dangerous types of superbugs, including a family of bacteria known as CRE. The Centers for Disease Control and Prevention says infections with these germs can be extremely difficult to treat and could be deadly in up to 50 percent of patients who become infected.

Peter Pitts is the president of the Center for Medicine in the Public Interest. He says this one case could turn into thousands unless we do something now. "Shame on us to wait until there are bodies in street to begin to worry about this," said Pitts. "The thing about antibiotics is that we currently have a pretty good supply of various potencies, but you always need new ones. You can’t simply turn on the spigot when you think you need some and it comes out right away."

Pitts says the over-prescribing of antibiotics and the fact that there is no real incentive for companies to develop new antibiotics could lead to dire consequences.

So what does a future filled with drug-resistant superbugs look like?

"The more realistic view of this is that people get sick and have to be on a regimen of very strong antibiotics you know with very nasty side effects for extended periods of time," Pitts said.
Peter Loftus' article Combination Drug Therapies for Cancer Show Promise at Higher Potential Cost relies on opinion rather than facts. And the opinion he relies on comes from an organization that combines factoids with fiction to demonstrate that new drugs are too expensive. 

1.    The assertion of Steve Pearson of the Institute for Clinical and Economic Review (ICER) that the combinations will cost more is inaccurate.  In a recent report I pointed out that Pearson estimates the cost of combining three drugs for multiple myeloma using list prices of all drugs in making the case for ‘group’ discounts.   In fact, the list price of such medicines are already discounted by about 30-50 percent because of rebates drug companies provide.  Pearson never notes that these rebates are pocketed by insurers and pharmacy benefit companies even as they force patients to pay 30 percent of the list price of products. 

2.    Most treatment combinations reduce the cost of other more expensive services and care.  Indeed, I co-authored two abstracts presented at the same ASCO meeting Loftus attended demonstrating that combinations of cancer drugs matched to specific patients cost less or about the same at less effective treatments.  Similarly, Intermountain Health published two studies the came to the same conclusions. 

3.    Pearson and others also ignore the savings and benefits to patients by using combinations that reduce the need for second and third line therapies as well as the end of life care that is more likely required when combinations are not used. 

4.    Finally, cancer costs increase mainly because people are living longer.  ICER notes “…additional progression-free survival leads to higher costs” and recommends restricting use of new medicines to address this ‘problem.’  So letting people die becomes the de facto discount. 

Groups like ICER believe that we need to spend less on cancer drugs they define as not valuable because doing so " often leads to waste that saddles our children and their children with future budget deficits based on our inability to objectively look at the evidence and value of new drugs. We’re siphoning off resources for other things we need like better schools and more resources for local police, roads and bridges."

In fact, spending on cancer drugs – which is less than 1 percent of total health care spending – increases well-being and prosperity by increasing life expectancy.   Reporting based on misinformation could lead to policies that deny patients access to medicines that produce such benefits including more tax revenue for filling potholes.   Loftus and other journalists should look at how ICER leads them astray.  Also, has anybody checked to see if ICER doesn't run a highway construction company?

Serepta and the Final Furlong

  • 06.07.2016
  • Peter Pitts
Sarepta Therapeutics said the U.S. Food and Drug Administration has requested for additional data from an ongoing study for its muscle-wasting treatment as the agency decides whether to approve the drug or not.

"We believe there is a good chance these data will demonstrate required dystrophin production and recommend shares ahead of a regulatory decision, which could come in 2016," they said in a Monday note to clients.

The FDA deferred a highly anticipated decision on whether to approve Sarepta's drug, eteplirsen, last month, after an advisory panel determined that the treatment was not effective.

The agency requested that Sarepta provide dystrophin data from biopsies already obtained from the ongoing confirmatory study of eteplirsen, the company said on Monday.

Sarepta's drug has been in the spotlight over the past few months with patient groups and parents arguing passionately in favor of the treatment to pressure the regulator to approve the drug.

Duchenne muscular dystrophy is a rare genetic disorder characterized by progressive muscular weakness and is caused by a lack of dystrophin, a protein needed to keep muscles healthy. Eteplirsen is designed to increase the production of dystrophin.

Sarepta said on Monday it plans to submit data from thirteen patient biopsy samples to the FDA over the coming weeks to facilitate a prompt decision by the agency.

Expediting Expanded Access

  • 06.03.2016
  • Peter Pitts
Yesterday, the FDA clarified its expanded access policies in a series of documents including a Q&A that outlines the process of obtaining expanded access, guidance that describes how companies may charge for therapies given under expanded access programs, and a new form to request access to investigational drugs.
FDA Commissioner Robert Califf said the agency hoped to simplify and streamline the process to reduce "procedural burdens on physicians and patients."

In one document, the agency outlines requirements for physicians and companies to obtain expanded access for individual patients, or for intermediate or large-scale studies. The document notes that FDA requires IRB review of all expanded access protocols, even in cases of emergency use, as well as reporting of adverse events.
 Addressing concerns from drug sponsors that adverse event reports from expanded access programs could derail development efforts, the agency said that while adverse event reporting from expanded access protocols have been included in drugs' safety assessments in a "small number of cases," FDA reviewers are to interpret safety data in "the context in which the expanded access use was permitted."

In another guidance addressing the process of charging for investigational therapies, FDA said companies must provide evidence that a trial could not be conducted without charging, that the treatment has a potential clinical benefit, and that data obtained from the trial are "essential" to establishing the therapy's safety or efficacy. The company must also submit a calculation of cost recovery. 
In 2013 draft guidance, the agency had said companies can only charge for direct costs involved in making an investigational drug available, and only when the costs of providing the drug are "extraordinary" for the company. The new guidance reiterated both points.

FDA also finalized an Individual Patient Expanded Access Investigational New Drug Application form to speed individual requests for investigational drugs. Califf said the new, "much shorter form" should take physicians about 45 minutes to complete.

Ed Silverman at noted that the Washington state Medicaid program has been ordered to lift restrictions on coverage of pricey hepatitis C treatments, according to a preliminary injunction issued Friday by a federal judge in Seattle.
In a strongly worded, 12-page opinion, United States District Court Judge John Coughenour agreed with their argument. He wrote that the facts “clearly favor” their contention that state policy violates federal law. In his view, the evidence “establishes that there is a consensus among medical experts and providers that the life-saving [drugs] are medically necessary” for all hepatitis C patients.”
The restrictions were developed by ICER.
Last week ICER’s boss Steve Pearson told attendees at a meeting to vote on the value of new myeloma drugs that ICER’s recommendations are not used by health systems or insurers to make coverage decisions.
In fact, ICER recommended reducing access to Hep C drugs to control spending:
"The budget impact and cost offset figures change substantially under our second treatment
scenario in which only patients with advanced liver fibrosis are started on the new treatment
regimens, with other patients treated with existing pre‐DAA regimens."
"Panel members and outside experts nearly all agreed that for both clinical and cost reasons,
not every patient with hepatitis C needs to be immediately treated with the new drugs.
Informed, shared decision‐making about the timing of treatment should be encouraged.
Given the circumstances, it is reasonable to consider prioritizing treatment with the new
drugs for patients who need urgent treatment and have some evidence of liver fibrosis but
do not have advanced liver disease.
The Washington State Healthcare Authority (WHCA) restricted Medicaid access to Hep C drugs by following the ICER recommendation.
It was sued and a federal judge ordered the WHA to make Hep C drugs available to everyone.
Here’s what the court said about WHA’s hewing to the ICER guidance:
“defendant does not come forward with any specific, credible evidence to show that its decision to apply the HCV Treatment Policy’s exclusion of DAA treatment for patients with F0-F2 fibrosis scoring is based upon medical evidence rather than solely budgetary concerns.
Or concerns of what ICER refers to as health system value. 
ICER claims the provisional health system value is grounded in “the assumption that society would prefer health care costs to grow at a rate that does not exceed growth in the overall national economy. “
Here’s what the court said about THAT:
The WHCA argues that the injunction would double the State’s Medicaid outpatient Pharmacy budget and cause them to reduce Medicaid enrollments, benefits, or provider rates to compensate for the increased expenditure in HCV treatment. (Dkt. No. 29 at 22.) The Ninth Circuit has also addressed the question of balancing the risk of irreparable harm with the risk of financial hardship for the enjoined institution. Posed with this question, the Ninth Circuit held that when “[f]aced with such a conflict between financial concerns and human suffering, we have little difficulty concluding that the balance of hardships tips decidedly in plaintiffs’ favor.” Lopez v. Heckler, 713 F.2d 1432, 1437 (9th Cir. 1983)
ICER’s involvement or influence on WHCA is not just intellectual.  ICER is one of three organizations that WHCA pays to conduct technology assessments:
“The mission of the Washington State Health Care Authority’s Health Technology Assessment Program is to ensure that medical treatments and services paid for with state health care dollars are safe and proven to work.  The program contracts for scientific, evidence-based reports about whether certain medical devices, procedures, and tests are safe and work as promoted, and an independent clinical committee of health care practitioners then uses the reports to determine if programs should pay for the medical device, procedure, or test.  The clinical committee has a legislative mandate to consider, in an open and transparent process, evidence regarding the safety, efficacy, and cost-effectiveness of the technology being reviewed.
In 2012, ICER was named one of the program’s three Technology Assessment Centers and completes one to three assessments a year for the agency.  To date, ICER has completed projects on cervical spinal fusion for degenerative disc disease, cardiac nuclear imaging, proton beam therapy, appropriate imaging for breast cancer screening in special populations, and bariatric surgery.”
ICER has tried to distance itself from the boasts it has made in the past that it serves at the pleasure of PBMs and insurers.  But as my friends at recently pointed out: ICER boss Steve Pearson told "ICER’s framework is specifically designed for payers," Dr. Steven D. Pearson, recently admitted in an interview with Evidence-Based Oncology’s managing editor Surabhi Dangi-Garimella. That statement is a direct quote and says everything patients need to know about the independence and value of ICER's tools.”
And now we know that ICER is a paid consultant to the government agency that used the ICER value framework to ration drugs.  My guess is ICER will not take responsibility for WHCA’s illegal drug rationing and the harm caused to patients that prompted the court’s decision. That assertion, as well as ICER's claim that it is a trusted third party should be regarded with great suspicion.  

As for patients, it's time to follow suit literally, and take legal action against other insurers and government systems that use ICER to justify illegal rationing. 

It's the Volume Stupid..and the Rebates

  • 06.02.2016
  • Robert Goldberg
An IMS report on Oncology Drug trends was released today. 

I guess it was too much to ask for the media to actually read the full report or report on the full report.  It's easier to feed into the drug spending is unsustainable and creates financial toxicity narrative..  Meg Tirrell came closest to getting it right, noting that most of the increase was due to more people taking new medicines for longer.  

The report breaks it down thusly
  • Over the past five years, the cost of oncology medicines in the U.S. increased by $15.9 billion, or 72% over the 2010 level. Over $9 billion of total growth came from the adoption of new therapies introduced since 2010 and a similar amount is due to increased volume and price of existing branded drugs.
  • Greater use of older brands – due to increasing numbers of patients receiving treatment as well as lengthening treatment durations – led to $9.3Bn in cost growth in the past five years.
Payers are also noticing the impact on drug budgets of longer treatment duration and increased numbers of patients receiving treatment.

What Meg didn't mention and should have because she brought up financial toxicity is that cost sharing for cancer drugs is that insurance imposed cost sharing soared by 30 times more than prices net of rebates..  I just compared the out of pocket data from the IMS report on Developments in Cancer Treatments, Market Dynamics, Patient Access and Value from May 2015 (page 35) with data in the report the media is writing about. 

And rebates remain about 40 percent of the total increase in cancer drug spending.  None of that money directly goes to cancer patients.  At the same time, drug companies are helping patients with out of pocket costs. 

Meg alluded to it.  Most other reporters didn't.

Rebates up.  Cost sharing up.   Someone is making a lot of money and sticking it to patients.  

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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