Paving the Regenerative Medicine Pathway

11/17/2017 03:19 PM | Peter Pitts

FDA unveiled a regenerative medicine framework aimed at speeding the development and review of cell and stem cell therapies and tissue-based products, while also cracking down on those that would game the system. The framework, which was outlined in two draft and two final guidances, builds on the agency's previous policy that took effect in 2005.

"Today we’re taking steps to advance an innovative framework for how we intend to apply the existing laws and regulations that govern these products," FDA Commissioner Scott Gottlieb said in a statement. "Our aim is to make sure we’re being nimble and creative when it comes to fostering innovation, while taking steps to protect the safety of patients."

The two final guidances aim to provide clarity on which products are exempt from FDA regulations, and how FDA defines "minimal manipulation" and "homologous use."

The first draft guidance clarifies regulatory pathways for devices used in the recovery, isolation, or delivery of Regenerative Medicine Advanced Therapies (RMAT). In the second draft guidance, FDA explains how it might consider regenerative medicine products for expedited review pathways, including Fast Track, breakthrough therapy and RMAT designations, as well as accelerated approval and Priority Review.

The RMAT designation, which was introduced in December as part of the 21st Century Care Act, applies the principles pioneered in FDA’s breakthrough designation to regenerative therapies including “cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products.” In August, Gottlieb announced that FDA will also make some gene therapies eligible for RMAT.

The second draft guidance also proposes the use of "innovative" trial designs, such as basket trials that compare multiple investigational products. Another example is a multi-center trial where individual academic centers use the same manufacturing protocols and share combined trial data to support BLAs from each individual center.

"Our goal is to achieve a risk-based and science-based approach to support innovative product development, while clarifying the FDA’s authorities and enforcement priorities and making sure we are protecting patients," Gottlieb said in his statement.

The second draft guidance also encourages companies to engage with Center for Biologics Evaluation and Research (CBER) review staff during product development. Several companies have voiced concern over the frequency of interaction with FDA, particularly regarding preclinical development of regenerative medicine therapies. In a media briefing Thursday, Peter Marks, director of CBER, said that the guidances aim to address this by providing clarity on “the agency’s interpretation of the regulations.”

FDA did not issue any new warning letters or enforcement actions with the guidances, but said it intends to focus enforcement actions for unlawfully marketed regenerative medicine products on those that pose a higher risk, considering factors such as whether it is for allogeneic use and the route and site of administration. Gottlieb said that providing a clear regulatory framework for developers "gives us the solid platform we need to continue to take enforcement action against a small number of clearly unscrupulous actors."  Read More & Comment...

Alex Azar rounds out HHS 'Dream Team'

11/13/2017 11:08 AM |

The Trump administration has received kudos for the appointment (and performance of) CMS Administrator Seema Verna and FDA Commissioner Scott Gottlieb.

Nominating Alex Azar to by HHS Secretary is a trifecta for the agency.  The media will make much of his Eli Lilly background.  Here we focus on his stellar public service: 

"From 2001 until February 3, 2007, Azar worked at the U.S. Department of Health and Human Services, first as the General Counsel of the Department (2001-2005), and then as the Deputy Secretary of Health and Human Services (2005-2007).[8][9] He was twice confirmed unanimously by the U.S. Senate. As Deputy Secretary, Azar worked closely with Secretary Mike Leavitt as the number two official and Chief Operating Officer of the largest civilian department in the federal government, with a budget of $698 billion and more than 66,000 employees reporting up to him.[10]

On behalf of Secretary Mike Leavitt, Azar supervised all operations of HHS, including the regulation of food and drugs, Medicare,Medicaid, medical research, public health, welfare, child and family services, disease prevention, Indian health, mental health services, emergency preparedness and response, and many other activities. Agencies that reported to him included, among others, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, the National Institutes of Health and the Centers for Disease Control and prevention. Azar led the development and approval of all HHS regulations. He was a member of the Deputies Committees of the White House Homeland Security Council, National Economic Council, and Domestic Policy Council, and an ad hoc member of the Deputies Committee of the National Security Council. He also represented the Secretary on the Board of Governors of the American Red Cross and the Board of Trustees of the John F. Kennedy Center for the Performing Arts"  Read More & Comment...

Insurers and PBMs Undermine Oral Parity Laws

11/13/2017 10:01 AM |

As recent study by University of North Caroline researcher Stacey Dusetzina and her colleagues found that patients paying the most for their cancer pill prescriptions experienced increases in their monthly out-of-pocket costs. For those whose costs were more expensive than 95 percent of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90 percent of what other patients paid saw their costs increase by $37.19 per month.

The proportion of medication fills requiring patients to spend more than $100 per month out-of-pocket increased from 8.4 to 11 percent for plans subject to parity laws, while plans outside of the laws saw a slight decline.

Dusetzina said that one issue that may be impacting cost is that the parity laws do not address the affordability of cancer drugs.

Indeed, what good is parity if PBMs and health insurers continue to shift every patient who needs cancer drugs into the co-insurance or highest cost sharing tier?

Adam Fein's analysis of cost shifting underscores why oral parity is being undermined: 

"In the charts below, I summarize employers’ 2017 pharmacy benefits by examining (1) cost sharing tier structures, (2) average copayments, by formulary tier, (3) type of cost sharing (coinsurance and copayment), and (4) coinsurance structures. I’ll investigate the growing role of deductibles in a follow-up article.

This year’s results show massive cost-shifting for specialty drugs. For the first time, a majority of plans have four tiers. Economically-debilitating coinsurance—in some cases with no limit on out-of-pocket expenses—is common.

When people complain about “drug costs,” they are actually thinking about the share of costs that they pay. Last week, I highlighted Prime Therapeutics’ data showing very slow growth in post-rebate drug spending. Given the new Kaiser/HRET survey, it looks like patients may not always be getting the benefit of lower costs."

The problem is that much of the price of drugs is being used to subsidize rebates and discounts for PBMs and insurers and the copay assistance required by higher cost sharing.   Drug companies are paying rebates and then paying for the markup on the rebated prices at the backend.  Where's the incentive to reduce patient costs?  Consumerization requires a business model that rewards consumers, instead of exploiting them. 

  Read More & Comment...

PBMs and Insurers Undermine Oral Parity

11/13/2017 11:02 AM |

A recent study by University of North Carolina researcher "Stacey Dusetzina and her colleagues found that patients paying the most for their cancer pill prescriptions experienced increases in their monthly out-of-pocket costs. For those whose costs were more expensive than 95 percent of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90 percent of what other patients paid saw their costs increase by $37.19 per month.

The proportion of medication fills requiring patients to spend more than $100 per month out-of-pocket increased from 8.4 to 11 percent for plans subject to parity laws, while plans outside of the laws saw a slight decline.

Dusetzina said that one issue that may be impacting cost is that the parity laws do not address the affordability of cancer drugs."

Indeed, what good is parity if PBMs and health insurers continue to shift every patient who needs cancer drugs into the co-insurance or highest cost sharing tier?

Adam Fein's analysis of cost shifting underscores why oral parity is being undermined: 

"In the charts below, I summarize employers’ 2017 pharmacy benefits by examining (1) cost sharing tier structures, (2) average copayments, by formulary tier, (3) type of cost sharing (coinsurance and copayment), and (4) coinsurance structures. I’ll investigate the growing role of deductibles in a follow-up article.

This year’s results show massive cost-shifting for specialty drugs. For the first time, a majority of plans have four tiers. Economically-debilitating coinsurance—in some cases with no limit on out-of-pocket expenses—is common.

When people complain about “drug costs,” they are actually thinking about the share of costs that they pay. Last week, I highlighted Prime Therapeutics’ data showing very slow growth in post-rebate drug spending. Given the new Kaiser/HRET survey, it looks like patients may not always be getting the benefit of lower costs."

In another blog Fein notes: "For 2017, about 8 out of 10 U.S. workers must meet a general annual deductible before their plan pays for most healthcare services. Prescriptions are typically excluded from the deductible.

However, this year’s survey shows that one-third of workers in high-deductible plans now faces a separate prescription drug deductible. These plans shift 100% of the prescription cost to the patient until the deductible is met.

After reviewing the latest data, I offer some observations on how deductibles are altering the pharmaceutical and pharmacy industries. The bottom line: Patients who must cover the costs of their drugs shop for better deals and cheaper pharmacies. Get ready for the consumerization of the pharmacy industry!"

The problem is that much of the price of drugs is being used to subsidize rebates and discounts for PBMs and insurers and the copay assistance required by higher cost sharing.   Drug companies are paying rebates and then paying for the markup on the rebated prices at the backend.  Where's the incentive to reduce patient costs?  The fact is, even if drug prices were cut, PBMs and insurers would still get their spread and increase cost sharing.   

Consumerization requires a model that rewards consumers instead of model screws them. (See below) 

  Read More & Comment...

Gottlieb to Pharma -- End the REMS "Shenanigans"

11/08/2017 09:24 PM | Peter Pitts

FDA Commissioner Scott Gottlieb Wednesday called on branded drug companies to “end the shenanigans” they use to block generic competition, and announced new steps to rein in some anticompetitive practices.

Speaking at a Federal Trade Commission meeting on competition in prescription drug markets, Gottlieb noted that drug companies sometimes prolong negotiation over terms of a shared REMS as a tactic to delay approval of generic drugs. To counter such practices, he said FDA is making it easier for sponsors of innovative drugs to cooperate with generic companies to implement a common master file for the implementation of a REMS.

The common REMS master file is a “first step toward making it easier to implement a single shared REMS,” Gottlieb said.

FDA published draft guidance entitled “Use of a Drug Master File for Shared System REMS Submissions” in the Federal Register Wednesday.

While a shared REMS will make it easier for providers to comply with the risk mitigation programs, they can also be used to prevent drug companies from prolonging negotiations with generic companies, Gottlieb said. “Our goal is to see sponsors share REMS systems to reduce burdens on providers. But when branded drug makers drag out these negotiations -- sometimes as a way to forestall generic entry -- we’re going to be in a stronger position now to say enough is enough.”

If branded companies fail to agree on terms of a shared REMS, FDA will “have a stronger basis to issue a waiver that will allow the generic drug makers to go their own way if they have to, and develop their own REMS,” he said at the FTC meeting. In a statement issued to media, Gottlieb said FDA plans to provide more information on how and when generic companies can request a shared REMS waiver and the factors FDA intends to consider.

At the meeting, Gottlieb also vowed to use FDA’s bully pulpit to deter supply chain intermediaries like specialty pharmacies from helping pharma companies deny generic manufacturers access to samples that are needed to conduct FDA-required tests. Gottlieb said he is “going to contact pharmaceutical supply chain intermediaries to inform them of the FDA’s interest in making sure that generic firms can gain access to the doses they need to run bioequivalence studies. When intermediaries sign on to these restrictive games, I want them to know that they’re challenging a broader public health goal.”

Gottlieb made a public health case for competitive drug markets. “Our economic model, which rewards highly innovative drugs with the opportunity to hold monopolies for a limited period of time through patents and exclusivities, and to freely price their products to a measure of the value that a transformative drug offers, also depends on the generic approval process working as intended,” he said. “It depends on the ability to have vigorous competition once those patents and exclusivities have lapsed.”

Comments on the draft guidance are due in 60 days.
   Read More & Comment...

Patient For Affordable Drugs Founder Fails to Disclose Funding Source to FTC

11/07/2017 03:18 PM |

David Mitchell, the fact-challenged founder of Patients for Affordable Drugs has never been one to spend more than a nanosecond with the truth when it comes to discussing the value of medical innovation. 

He also is allergic to being transparent about his background and funding. Either that or he is exceedingly modest.   Mitchell is speaking at an FTC meeting entitled, “Discussion: Potential Next Steps to Encourage Entry and Expand Access through Lower Prices."

Here's his bio for that event:

David has 40 years of experience working on health care and public health policy as a communications specialist. He has worked to reduce teen smoking, increase use of seat belts, to fight drunk driving and improve child health and safety. He helped build and run for more than 30 years GMMB—a cause-oriented, public policy communications firm in Washington, DC. He retired in 2016 to focus his full energy and attention on helping bring about policy change to lower drug costs. You can follow him on Twitter here. Email him at david@patientsforaffordabledrugs.org

Here's what he left out: 

Received nearly $60 million in federal contracts after Obama took office, according to an analysis by The Daily Caller News Foundation Investigative Group.

$200 million from the Clinton campaign in 2016 and $389 million from the Obama campaign in 2012

$12 million from Phrma to run pro-Obamacare ads. 

Nearly $700 million to promote Obamcare enrollment. 

My favorite: $575K to run ads in Jewish news outlets in support of the Iran nuclear deal.

These tidbits are important because it provides some clues about why David would get $500K from the Laura and John Arnold Foundation to set up a patient group. 

Indeed, it is curious that in his FTC bio, David left out important background information about his group.   Patients For Affordable Drugs claims it " is the only independent national patient organization focused exclusively on achieving policy changes to lower the price of prescription drugs."

First, it is not independent.  It receives 87 percent of its funding from one source:  the aforementioned Laura and John Arnold Foundation (LJAF).  Second, it cooperates and coordinates with other LJAF grantees including ICER and Harvard's Aaron Kesselheim.  ICER mind you have deemed most new cancer drugs marginally effective and too expensive despite evidence to the contrary.  Have you heard P4AD challenge ICER?  You haven't and you won't because they get cash from the same cow. Third, Mitchell's funding is never disclosed when media outlets that also receive LJAF money to run stories about drug prices quoting him.  That's deliberate. 

Further, it is NOT true that it is the only group pushing for lower drug prices.  On the contrary, many other patient organizations who, in addition to providing counseling, funding basic research and covering expenses for cancer patients, have pushed for policies that would reduce the time and cost of drug development and promote generic competition.  P4AD is silent on accelerating innovation at the FDA.  Moreover, while other groups have fought for caps on drug copays, the elimination of step therapy, passing rebates directly to patients, PFAD has paid lip service to these issues. 

It is simply a media outlet for dog whistle messaging about drug prices.  Mitchell loves to say he is grateful for medical innovation as a myeloma survivor.  But many would argue (including me) that the policies he is promoting have been proven to marginally reduce prices but substantially limit access and future innovations.  

Nobody disagrees with the goal of reducing health care costs and drug prices.  But P4AD is a hollow advocacy group that does nothing to advance FDA and reimbursement reforms to would make new medicines less expensive and more affordable.  By excluding the Arnold affiliation and GMMB's main revenue sources, David is trying to portray himself as a lonely crusader against big Pharma.   There's very little truth in that depiction. 

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Taxing Orphans

11/03/2017 09:36 AM | Peter Pitts

How do you spell "mistake?"

The new tax bill would eliminate tax credits used to develop rare-disease drugs. Currently, drug makers get allowed a tax credit of up to 50 percent of certain research costs for rare-disease drugs. The new tax bill would repeal the credit, which falls under the Orphan Drug Act, “for certain drugs, for rare diseases or conditions” starting after this year.
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OW THAT’S A PATIENT-CENTERED VALUE FRAMEWORK

10/30/2017 12:24 PM |

An op-ed I was honored to co-author with BIONJ's CEO, Debbie Hart.    

Article was originally published in the New Jersey Spotlight
You can learn more about BIONJ here: 

OP-ED: NOW THAT’S A PATIENT-CENTERED VALUE FRAMEWORK
DEBBIE HART AND ROBERT GOLDBERG | OCTOBER 27, 2017
Insurance companies often use value frameworks to steer all patients to the least-expensive products, erecting barriers to obtaining recommended treatments


There’s been a lot of discussion about using “value frameworks” to reduce the cost of drugs and increase patient access. Value frameworks are being proposed as tools to determine which medicines will be covered, reimbursed, and made available to patients. Value-assessment frameworks attempt to assess therapeutic options based on clinical benefits, health outcomes, value to the patient, and effectiveness, compared with other potential treatment options … all in the context of cost.  Unfortunately, such evaluations assume that on average, everyone will respond to all drugs in the same way. In fact, the same treatment can have different benefits to different patients, depending on their genetics, combination of diseases, severity of illness, age, gender, and race.   

Moreover, value frameworks are used by insurance companies to steer all patients to the least-expensive products by imposing higher cost-sharing and more barriers to obtaining recommended treatments, even if the other drugs are not as effective or oftentimes, don't work. Coverage is already constrained through higher out-of-pocket spending, and step therapy (a patient must fail first on medicines specified by the insurance company before being eligible to receive the drug actually prescribed by the physician), and prior authorization. 

In addition, value frameworks, by limiting choice further, make it even more difficult to match people to the treatments that work best. And by measuring value simply in terms of reducing other healthcare spending, such frameworks are biased against the most vulnerable patients with few or no treatment options. Not every medicine will save money, but most medicines for people with rare, life-threatening, or disabling conditions improve the quality of life. In many instances, the first new treatment allows people to enjoy the opportunity for the next round of therapy that in turn, may increase well-being and save lives.

As Mark Fendrick, the godfather of value-based health insurance has stated, “the sickest patients are often those who face the highest financial burdens and the greatest obstacles to access.” Where is the value there?

That is not to say that the cost and benefits of new products should escape scrutiny. BioNJ welcomes the opportunity to discuss the true value of medical innovation and demonstrate the importance of enabling meaningful access to innovative medicines that benefit the entire healthcare system, the economy, and society as a whole. 

Long-term impact
But value frameworks ignore the long-term impact of new medicines in setting prices and rationing access. The formulations being used do not take into consideration that increasing the number of healthy people working, going to school, investing, and contributing to society will actually save healthcare costs and ensure a robust insurance system. 

We need healthcare coverage that concentrates on improving quality of life and averting loss of productivity and capability due to disease. Drug prices should reflect the differentiated worth of specific features or benefits that a new treatment provides and the ability to invest in future innovative medicines. This approach will encourage increased access and lower costs based on a new medicine's value and quality.

For example, Celgene CEO Mark Alles recently wrote that his company is “proactively working with major commercial U.S. healthcare payers on arrangements designed to give eligible patients access to our most recently approved medicine — a precision therapy with an accompanying diagnostic test — without deductibles, co-pays, and co-insurance. By partnering with payers to offset and even eliminate patient cost sharing as an obstacle to treatment, our hope is to prevent some of the financial burden that leads to many of the problems currently impacting patient care.”

For BioNJ, ensuring that “patients have the right treatment at the right time” for the greatest benefit is not just a slogan: It’s our vision. We owe it to patients to provide access to innovative medicines that are transforming the trajectory of many debilitating diseases and conditions.  

Consider that over the past 30 years U.S. cancer survivors have more than doubled to 14.5 million. HIV/AIDS — once a death sentence — is now a chronic manageable condition. Deaths from heart disease have declined by 50 percent. More recently, hepatitis C, once an incurable disease, can now be cured with one pill a day taken over four months.

In the absence of those medicines, healthcare would be more expensive, fewer people would be alive, and more people would live in pain.

That’s why with nearly 70 percent of medicines in the pipeline, potentially first-in-class therapies, the promise for increased life expectancy, improved life quality, and reduced healthcare costs is boundless. Because Patients Can’t Wait, BioNJ looks forward to working with insurers, consumers, employers, elected officials, physicians, and biopharma companies to speed the right medicines to the people who need — and will benefit from — them the most. Now that’s a patient-centered value framework!

Debbie Hart is president and CEO of BioNJ. Robert Goldberg, Ph.D., is vice president & co-founder of the Center for Medicine in the Public Interest.  Read More & Comment...

Thank You For Your Service? VA-ICER Partnership Breaks Shulkin's Promise to Veterans

10/27/2017 12:57 PM |

In testimony as the nominee to be Secretary of the Department of Veterans Affairs, Dr. David Shulkin promised: “There will be far greater accountability, dramatically improved access, responsiveness and expanded care options…. If confirmed, I intend to build a system that puts Veterans first and allows them to get the best possible health care wherever it may be – in VA or with community care.”
 
Sadly, less than five months into his appointment, Dr. Shulkin’s promise was broken when The VA’s Pharmacy Benefits Management Services office (PBMS) started partnering with The Institute for Clinical and Economic Review(ICER) set drug prices and limit veteran access to new medicines. 

According to ICER, the VA PBMS will use its “drug assessment reports in drug coverage and price negotiations with the pharmaceutical industry.”  But given ICER’s disregard of how patient’s value medicines the partnership has generated legitimate concern. 

The program’s directors - C. Bernie Good, Tom Emmendorfer and Michael Valentino recently churned out an incoherent and fact-free response to criticism of the partnership on the Health Affairs blog.  They defended the ICER partnership as contributing to the VAPBMS unsurpassed ability to provide the best medicines at the lowest cost.   They also claimed, with a straight face, that the VA health system provides better care than any other place.   As anyone who has read the book "Thank You For Your Service" or seen the movie version knows, quite the opposite is true.  And frankly, the "everything is perfect" tone of their blog suggests that they are more interested in sucking up to professional critics of the pharmaceutical industry then they are in helping making wounded warriors whole.  

In fact, ICER and VAPBMS are clearly more interested in using the VA as a model for determining drug prices and access nationwide.    The authors insist ICER evaluations will only be used to help the VA  authors set prices for new drugs.  That's nonsense.  The VA pharmacy benefits program already sets prices and restricts access to new medicines.  Under federal law, drug companies must the VA a price at least 24 percent lower than the best private sector price.  They also must give the VA rebates if prices go up more than inflation.   

So what is ICER's role likely to be? The authors assert that as “a federal organization, the VA lives within the reality of a fixed annual budget. Money spent well for high-value drugs (regardless of the overall individual cost of that drug or technology) is a good thing.” 

But that is not how the VA or ICER approaches access to new medicines. Apart from mandated price controls, the VA excludes some drugs and not others to get additional discounts.  This is an approach ICER has supported since its existence.  

Despite the authors' support of high-value medicines, the VA as consistently limited access to them at a great cost to patients.  A study by economist Frank Lichtenberg found that not only were 20 percent of drugs approved since 2000 covered by the VA and that the limited access was associated with lower life expectancy over age 65 compared to Medicare.  The innovation gap has grown since then.  Less access means more death. 

Indeed, since Lichtenberg did his study, the innovation access gap has gotten worse. A recent Avalere study found that "The VA National Formulary covers 54 percent of drugs on the California public employee retiree plan formulary, including 46 percent of brand drugs (102 of 222) and 61 percent of generic drugs (174 of 287.) " And it covers 50 percent few medicines than most state Medicaid plans. 

Yet, the authors claim lots of people get access to drugs not covered under the VA formulary.  Also, untrue. Getting a drug that is not on the formulary is difficult.  Most reviews are denied and over half take two weeks to process.  Veterans often have to travel hundreds of miles to get the medicine from a VA pharmacy.  

Indeed, the Inspector General's audit of the death of a lung cancer patient at a VA Southern Nevada Health System found that” patient had to travel 30 miles each way from his home to a system clinic for pharmacist review and approval of his physical prescription. " It took 14 days to get an off-formulary medicine approved.  In the meantime, the patient had to pay $4000 out of pocket for drugs.

ICER will only make the VA’s denial of timely, effective treatment worse, if that’s possible.   In the past, ICER reports have been used to limit access to cures for hepatitis C, drugs that reduce the risk of heart attacks and a wide variety of medicines for people with rare cancers.   ICER’s estimate of the value of medicine is so low that many of the drugs used to treat HIV would have been rejected by the group. 

The authors claim that VA patients get faster and broader access to HCV drugs than commercial patients.  But until this year, the VA used the ICER guidelinesto limit access to a cure.    As a Newsweek article reported, a VA memo recommended treating those with advanced liver disease but holding off for patients with mild cases of the illness.  ICER’s recommendations are meant to save money, not save lives.  And when the VA started paying for drugs, cure rates went up.  

New medicines are what reduce the total cost of care and mortality. Price concessions and budget caps obtained by limiting access come at the expense of the most vulnerable and sickest people. If the VA uses ICER’s rationing scheme it will not only break Dr. Shulkin’s promise, it will darken and damage the lives of those veterans who need the VA the most.  





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Utah's Importation Jazz

10/26/2017 12:44 PM | Peter Pitts

Per Ed Silverman over at Pharmalot:

Seeking a way to alleviate high drug prices, a Utah lawmaker hopes to introduce a bill that would allow the state to import prescription medicines from Canada, a move that is likely to accelerate a fierce debate over drug costs and patient safety.

Over the next several weeks, Rep. Norman Thurston, a Republican, plans to submit legislation to authorize state officials to designate an existing pharmaceutical wholesaler to purchase prescription drugs from a wholesaler in Canada. His hope is that retail pharmacies based in Utah would then be able to buy and sell medicines at lower prices.

“We’re still trying to work out some of the details, but we envision a safe supply chain that would result in significant cost savings for the citizens of Utah,” he told us. To allay safety concerns, he envisions the bill would require prescription medicines to be approved by regulators in both Canada and the U.S.

“And the bill would establish a chain of custody just like we have for U.S. distribution,” he said. “It shouldn’t be a significant cost to the state to set up a program, fill out paperwork and get approval (from the U.S. Human and Health Services secretary). According to federal law, that’s the only approval we need.”

Even so, the move is likely to receive considerable pushback.

In general, importation sparks debate that Americans could be exposed to counterfeit medicines.

Last year, four former Food and Drug Administration commissioners penned an open letter arguing against importation, citing such concerns. And the pharmaceutical industry has regularly lobbied against any and all efforts to allow importation. Over the years, Congress has failed to pass various bills that were proposed. And more than a decade ago, several states pursued web sites to allow residents to purchase medicines from Canada, but those efforts eventually sputtered, as well.

“Good luck with this. No HHS Secretary of either party has ever declared that importation is safe,” said Peter Pitts, a former FDA associate commissioner who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by the pharmaceutical industry.
“We have a closed regulatory system. Health Canada may be world class, but it doesn’t mean we can have multiple standards for drug approvals. What matters is how a drug is manufactured, stored, and dispensed. It sounds easy, but is extraordinarily hard.”

For his part, Thurston is doggedly optimistic.

In this instance (as it generally is with schemes to advance importation, “doggedly optimistic” = “deaf and dumb to reality.”

Let’s cut right to the chase. Generic drugs (85% + of all medicines volume in the US are LESS expensive than in Canada or any European country. Next, for the overwhelming number of Americans with private health insurance, the co-pays for their products are LESS expensive then buying them retail at either a brick-and-mortar of Internet Canadian pharmacy. Biologics? 85% of all biologics are administered in hospitals. Is Senator Sanders suggesting that American hospitals should import drugs that may or may not have been shipped under proper refrigeration conditions? FDA inspections speak otherwise.

The on-the-ground reality of state and local importation schemes has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX” program? Over 19 months, only 3,689 Illinois residents used the program—that’s .02 percent of the population.

And what of Minnesota’s RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That’s in a state with a population of 5,167,101.

Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well, the city of Springfield has been out of the “drugs from Canada business” since August 2006.

And speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”

The Canadian supplier for the program was Winnipeg-based Total Care Pharmacy. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.

Programs like this wouldn’t do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation’s spending on prescription medicines a whopping 0.1 percent—and that’s not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally involved in foreign drug importation schemes.

In addition to importing foreign price controls, Americans would end up jeopardizing their health by purchasing unsafe drugs while not saving money.

A better policy for our new President and Congress to focus on is the issue of increasing insurance company co-pays and co-insurance. Dropping drug co-pays would also help patients stick to their prescribed treatment regimes. All too often, people skip a dose, don’t get a refill, or stop taking their drugs prematurely in order to save money. In the long run, though, not adhering to a drug regimen leaves patients less healthy — and increases national medical expenses by an estimated $300 billion annually.

When consumers say, “My drugs are too expensive,” what they mean is that their co-pays and co-insurance are too expensive. And they’re right. Major insurance companies and pharmacy benefit managers (PBM) receive significant discounts from the manufacturers. So why doesn’t this result in lower co-pays for consumers? That’s a good issue for our new political leadership to debate – both in Salt Lake City and Washington, DC.
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The Similarity Conundrum

10/25/2017 09:37 AM | Peter Pitts

Biosimilarity? No one said it was going to be easy.

A smart and timely cross-post from RAPS ...

Sandoz Raises Questions With FDA Draft Guidance on Statistical Approaches for Biosimilars

Martin Schiestl, chief science officer at Novartis' Sandoz, on Tuesday explained how the US Food and Drug Administration's (FDA) draft guidance on statistical approaches to evaluate analytical similarity poses risks that could end up causing true biosimilars to be rejected randomly.

Schiestl told attendees of DIA's biosimilars conference in Bethesda, MD, that the problem is related to equivalence testing, which FDA says in the draft, "is typically recommended for quality attributes with the highest risk ranking and should generally include assay(s) that evaluate clinically relevant mechanism(s) of action of the product for each indication for which approval is sought." 

The draft, released about a month ago, also notes: "Determining an appropriate margin is a critical but challenging step for equivalence testing in any setting. Ideally, it would be possible to establish and pre-specify a biologically or clinically meaningful equivalence margin based on scientific knowledge or past experience. Often, however, such a margin is not readily available for every quality attribute deemed important enough for Tier 1 testing in a biosimilar development program. With this limitation, FDA currently recommends use of an equivalence margin that is a function of the reference product's variability for the attribute being tested."

But Schiestl noted that monitoring the mean is useful in process development and post approval process monitoring.

However, for lot release decisions, "Compliance with a preset mean is an impossible criteria."

He added, "Strict adherence to equivalence testing for Tier 1 attributes makes biosimilar development a gamble. Justifications which may overrule a failed equivalence test should be added in the guidance."

Such justifications may include a scientific understanding of a variation and an "inconsistent mean of the reference product which might be caused by inherent process fluctuations within acceptable ranges, manufacturing changes or movements within a design space," Schiestl added.  Read More & Comment...

Cigna Signals

10/18/2017 03:09 PM | Peter Pitts

Last week’s commentary on Cigna’s plan to replace Oxycontin ER with Xtampza ER on its core formulary (Is Cigna Trading Patient Choice for Hidden Profits?) resulted in a very open and honest chat with a senior Cigna executive. He assured me that patient co-pays wouldn’t go up for Xtampza ER and that if a patient stays on Oxycontin after prior authorization, that the co-pay would also stay the same. So, good news for patients there.

I asked how this change in tiering would “guard against opioid abuse” (since both products are formulated with properties designed to deter intranasal – snorting, and intravenous -- injection abuse, and one isn't "better" than the other). The answer was that, because of the value-based contract, Collegium would be rewarded for “appropriate prescribing.” But since Collegium (the manufacturer of Xtampza ER) doesn’t prescribe (they sell) would their role be in detailing “best practices?” The executive didn’t know -- but promised to get get back to me with an answer. So, watch this space for more details.

I also mentioned to him that Purdue Pharma (as far as I know) is the only company actively detailing the CDC Opioid prescribing guidelines. The CDC guidelines seem to be a baseline requirement for enhanced physician education, and who better to do this than the manufacturers who are detailing directly to them? While the process in the development of the guidelines was not as transparent as they could have been, the guidelines themselves are a sensible foundation. Hopefully Cigna’s deal with Collegium will drive better prescriber awareness.
   Read More & Comment...

Why indeed? Why do we need drug rebates, anyway? A top lawmaker wants to know

10/17/2017 08:03 PM | Peter Pitts

From STAT News …
Why do we need drug rebates, anyway? A top lawmaker wants to know

WASHINGTON — Sen. Lamar Alexander has a question: why do we have drug rebates, anyway?

“Why do we need rebates?” the Tennessee Republican asked a panel of pharmaceutical industry representatives at a Senate committee hearing. The Health, Education, Labor, and Pensions committee met Tuesday morning for the second of three hearings on drug pricing, and heard testimony from five interest groups representing companies that play different roles in getting medicines to patients.

Rebates are payments made by drug manufacturers to “pharmacy benefit managers,”  middlemen that negotiate drug prices on behalf of companies, unions, and government agencies. PBMs come up with lists of drugs that receive preferred coverage from insurers and also arrange rebates from drug makers in exchange for favorable insurance coverage.

Sometimes the payments that drug manufacturers make to PBMs are passed on to insurers, and sometimes insurers pass on to patients the savings from those rebates. But the amount of those payments are kept secret.

Sound complicated and opaque? Alexander seems to thinks so too.

 “Why don’t we just get rid of rebates and let you negotiate directly with manufactures, take that $100 billion a year, and just reduce the list price?” Alexander asked Mark Merritt, president and chief executive officer of the Pharmaceutical Care Management Association, which represents pharmacy benefit managers. “Wouldn’t it be simpler for us to understand where the money goes?”

Alexander’s question seemed to betray a misunderstanding of the situation — as he admitted, “I have yet to figure out where [the money] goes” — because pharmacy benefit managers do negotiate directly with manufacturers to determine the rebate amount.

Merritt didn’t say yes or no, but classified rebates as basically “volume discounts,” enabling groups that purchase more drugs to get lower prices.
After the hearing, Merritt clarified to STAT that he would be open to axing rebates.

“We’d be happy if manufacturers would just go to lowering the actual price as opposed to rebating different suppliers and so forth,” Merritt said. “But I don’t see that happening anytime soon.”  Read More & Comment...

Gottlieb's Dueling Acronyms

10/12/2017 07:28 AM | Peter Pitts

And there are just as many reasons to say "yes" to HHS.

WHY GOTTLIEB SHOULD STAY AT FDA
BY STEVE USDIN, WASHINGTON EDITOR, BIOCENTURY

Reports that FDA Commissioner Scott Gottlieb tops President Donald Trump’s list for replacing ousted HHS Secretary Tom Price are reverberating around the Washington echo chamber. The speculation has made its way into so many articles, blogs, tweets and cellphone conversations overheard on the Red Line Metro cars frequented by lobbyists, lawyers and journalists that it has acquired a patina of credibility, even inevitability.

I don’t claim to know whether the job will be offered to Gottlieb or if he would accept it. I do think the interests of patients, FDA, regulated industry and, most likely, Gottlieb himself would be best served if he remains at FDA. Here are four reasons why:

1. FDA NEEDS A STRONG PERMANENT L EADER

FDA needs stable leadership to produce the regulatory innovation that can turn today’s scientific advances into tomorrow’s medicines.

While the agency can maintain critical functions on autopilot, only a congressionally confirmed leader can break new ground or take controversial steps. Gottlieb has started to take FDA in new directions, for example by making public health arguments for lowering drug prices by tackling pharma company “gamesmanship,” and for making cigarettes less addictive. He has announced plans to release a plan for advancing biomedical innovation that will go beyond the requirements in the recently enacted 21st Century Cures Act and FDA Reauthorization Act.

These projects reflect Gottlieb’s personal experience and vision. It will take years to get them started and on a firm footing. They would likely wither if he departed.

2. FDA NEEDS A COMPETENT LEADER

While there certainly are other individuals with the necessary experience and competence to lead FDA, there is no reason to believe they would be nominated if Gottlieb departed.

When Gottlieb was nominated, serious contenders for the position included individuals who want to discard the standards and principles that have made FDA the gold standard for medical product regulation. These guys are still out there, tanned, rested and ready for their opportunity to dismantle the regulatory state and make the world safe for purveyors of snake oil.

3. GOTTLIEB’S NOT RIGH T FOR HHS

Gottlieb lacks the kind of experience required to successfully manage an organization with a trillion-dollar budget and 80,000 employees.

Someone who has been a state governor or headed a state health department or possibly a large university system would be better qualified to deal with the massive budgets, to manage government departments with diverse missions and to placate members of Congress with competing interests.

4. HEADING HHS IS A THANKLESS TASK

The person who steps into Price’s shoes will be pinned between a mercurial president prone to humiliating cabinet secretaries, and feuding Republican factions in Congress that are promoting incompatible and impossible healthcare agendas.

The next HHS secretary will be castigated by Republicans for failing to strangle the Affordable Care Act and vilified by Democrats for failing to shore it up. The secretary also will have to defend the Trump administration’s proposals to slash funding for public health and biomedical research. It is difficult to imagine anyone coming out of the job with their integrity and self-respect intact.

If he departs now, Gottlieb will leave no mark behind at FDA, and there aren’t great prospects for advancing the public good at HHS. In contrast, based on his current trajectory, if he stays on the job, Gottlieb is on track to leave with a strong, positive legacy.  Read More & Comment...

JAMA Jive

10/11/2017 11:15 AM | Peter Pitts

From the pages of the Wall Street Journal …

A Flawed Study Depicts Drug Companies as Profiteers
Peter J. Pitts

Even the authors admit their selection criteria are a ‘critical limitation.’ That’s an understatement.

Are drug companies ripping off cancer patients? Of course they are, suggests a much-hyped study published last month in the journal JAMA Internal Medicine. The truth is more complicated.

Drug companies receive a staggering return on investment “not seen in other sectors of the economy,” write Vinay Prasad of Oregon Health and Science University and Sham Mailankody of Memorial Sloan Kettering Cancer Center. They estimate that pharmaceutical firms spend $720 million on average to develop a single cancer drug, while the average cancer therapy generates sales of $6.7 billion.

The editors at JAMA are brilliant physicians, but they could use a refresher on the economics of drug development. Several methodological flaws in the study lead the authors to underestimate drug-development costs. 
 
Messrs. Prasad and Mailankody examined 10 publicly traded companies that secured their first-ever Food and Drug Administration approval between 2006 and 2015. They pulled data on companies’ research spending and revenues from annual financial reports filed with the Securities and Exchange Commission. These selection criteria are a joke. By looking at 10 companies that produced only one cancer drug each, the authors screened out big multinational corporations that had previously secured FDA approval for one or more drugs. Small biotech firms that hadn’t secured FDA approval for any treatments were also excluded. 
 
The authors admit that the selection criteria are a “critical limitation.” No kidding: They only looked at 15% of all cancer drugs approved from 2006 to 2015, ignoring the other 85% of cancer therapies introduced that decade. This helped them “prove” their hypothesis.
 
The analysis also overlooks hundreds of millions of dollars of research spending at companies that never develop an FDA-approved medicine. Nine of every 10 publicly traded drug companies lost money in 2014, according to a 2016 International Trade Administration report. Most therapies don’t make it out of the lab and into clinical trials. Of those that do, only 12% are brought to market.
 
Those that defy the odds and win FDA approval don’t accurately represent the broader biopharmaceutical industry. Consider the success of these 10 drugs against those that are still going through clinical trials. Even if all of these companies’ other experimental drugs in the development pipeline failed, the success of this study’s 10 drugs would have resulted in an overall clinical approval success rate of 23%, twice the industry average.
 
Worse, five of the companies in question had purchased their drugs from smaller biotech firms. The authors didn’t count any of the research-and-development spending of these “nurturer” firms, only by the acquiring firm.
 
The other five drugs were developed entirely in-house—and the authors lowballed cost estimates for developing these drugs. Messrs. Prasad and Mailankody counted only two years of development costs before the first mention of the drugs in the medical literature. They figured this would accurately reflect preclinical costs, such as lab tests. 
 
Their assumption is wrong. In reality, the initial, preclinical research period often lasts four years or more. And for four of the 10 drugs examined, companies started lab research at least seven years before the first mention of the drug in any published medical studies. 
 
Drug development is much more expensive than the JAMA study suggests. More reliable is a November 2014 study from the Tufts Center for the Study of Drug Development. This more thorough examination estimates total research costs are about $2.6 billion for new cancer drugs. Politicians who advocate price controls undoubtedly will cite the JAMA study anyway. Never mind that government-imposed price caps would hamstring researchers and prevent the development of new treatments and cures.
 
In the past 17 years, biopharmaceutical companies have invented more than 550 FDA-approved medications. More than 800 experimental cancer drugs are currently under development at companies of all sizes, from tiny biotechs to giant multinationals. By misinforming readers, the JAMA study undermined the great work that drug companies are doing today.
 
Mr. Pitts, a former FDA associate commissioner (2002-04), is president of the Center for Medicine in the Public Interest  Read More & Comment...

Is Cigna Trading Patient Choice for Hidden Profits?

10/09/2017 10:28 AM | Peter Pitts

Here’s the CNN headline, “In an attempt to reduce opioid use amid a nationwide abuse epidemic, insurance giant Cigna will no longer cover most OxyContin prescriptions in its group plans beginning January 1.”

Cigna has signed a value-based contract with Collegium Pharmaceutical for the drug Xtampza ER, an oxycodone equivalent with abuse-deterrent properties. According to Cigna’s Chief Pharmacy Officer Jon Maesner "Our focus is on helping customers get the most value from their medications -- this means obtaining effective pain relief while also guarding against opioid misuse.”

That’s fine, but there’s one fact that’s strangely absent – both drugs, Oxycontin and Xtampza ER are equally “abuse-deterrent.” Here’s another important fact – OxyContin was reformulated and in 2013 and became the first opioid with FDA-approved labeling describing abuse-deterrent characteristics. Once the poster-child for abuse, Oxycontin is now at or near the bottom of the “junkie-preferred” chart.

It’s important to understand that both products are formulated with properties designed to deter intranasal (snorting) and intravenous (injection) abuse, but that neither is abuse proof -- and one isn't "better" than the other.

What Cigna isn’t saying is that it’s customers will no longer have access to a range of FDA-approved products with abuse deterrent properties -- limiting a physician’s options to help patients and address the opioid crisis via more personalized, appropriate therapeutic choices.

So, why the switch from Oxycontin to Xtampza ER? Could it be that Cigna negotiated a better deal with Collegium than it had with Purdue Pharma (the manufacturer of Oxycontin)? Unfortunately, this decision appears to be more about pharmaceutical rebates than “guarding against opioid misuse.”

Alas, Cigna’s hyperbole has been met with silence when it comes to pricing transparency.  Read More & Comment...

When it comes to Off-Label, let's not forget the role of Real World Evidence

10/08/2017 10:47 PM | Peter Pitts

Per this article from the Washington Post, it's important to note that "not doing additional clinical trials," as I was quoted as saying, does not mean ignoring a more regular and robust use of electronically collected and validated real world data to ascertain the performance of off-label use. The FDA is required by the 21st Century Cures act to develop standard protocols for the use of real world data -- and nowhere is this more crucial than in determining the safe and effective use of medicines via off-label prescribing.

Pressure mounts to lift FDA restrictions on off-label drugs
By Michael Ollove

When the Food and Drug Administration gives its okay for a new drug to be sold, it specifies the diseases or conditions for which the medicine has been approved. That does not mean doctors can’t prescribe that drug for other ailments. They do. All the time. And it’s perfectly legal.

But for decades drugmakers have been barred from promoting their drugs for uses that hadn’t gone through clinical trials. Worried about safety issues, the FDA has prosecuted numerous drugmakers for illegal promotion of off-label uses and extracted billions of dollars in fines and settlements.

Those restrictions could be giving way, perhaps in part because of the appointment of Scott Gottlieb as the new FDA commissioner in May. Before his nomination, Gottlieb, a physician and a resident fellow at the conservative American Enterprise Institute, advocated loosening the restrictions on off-label communications.

That’s exactly what Arizona did earlier this year when it became the first state to allow drugmakers to communicate directly with doctors and insurers about alternative uses of approved prescription drugs. Advocates for the loosening of the restrictions say they expect similar measures to be introduced in other state legislatures in the coming year.

These developments come on the heels of two legal cases in which federal district courts ruled that the First Amendment does not allow the FDA to prevent manufacturers from providing truthful information about their products to doctors.

Supporters say it makes sense to get rid of the restrictions on off-label drugs at a time when plenty of information and misinformation about prescription drugs is readily available to anyone with an Internet connection. And, they insist, who better to provide accurate facts about their products than their makers?

“We believe it’s a disservice to patients and physicians to prevent them from getting information from manufacturers who know their medicines best,” said Naomi Lopez Bauman, director of health-care policy at the Goldwater Institute, the libertarian think tank that devised the Arizona legislation and is promoting it in other states.

Bauman said she expects bills to be filed elsewhere in the coming year, but she refused to disclose which states Goldwater is targeting.

Many critics, however, remain firmly opposed to such efforts. “There have literally been dozens and dozens of examples of ­off-label uses of drugs encouraged by pharmaceutical companies in reckless ways that have led to substantial patient morbidity and mortality,” said Aaron Kesselheim, director of the Program on Regulation, Therapeutics and Law at Harvard Medical School.

Wide off-label use

Before a new drug can be sold in the United States, the FDA must affirm that it is safe and effective for specified uses, which are then described in the medicine’s labeling. But once a drug is approved, doctors are free to prescribe it for uses not specified in the labeling. That is because the FDA regulates products but not the practice of medicine.

Prescribing for off-label uses has become common. A 2013 study found that 30 percent of the prescriptions for oncology drugs were used for off-label purposes. Another found that 70 percent of a popular category of pediatric anti­psychotic drugs were prescribed for purposes not cited in the FDA’s approval of those medicines, including, for example, for the treatment of attention-deficit/hyperactivity disorder.

Sometimes the off-label use of prescription drugs comes to be considered the best treatment for certain conditions. “For some cancer drugs, the best therapeutic use is for off-label purposes,” said Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest, a nonprofit research and advocacy organization that is funded by the pharmaceutical industry.

One example is tricyclic antidepressants, a class of drugs that do not have FDA approval as treatment for nerve-related pain yet are considered by doctors to be the first choice of drugs for that purpose.

Nevertheless, a recent study published in the journal JAMA found a higher incidence of adverse drug effects from off-label use than from on-label use.
Pitts does not think the FDA should prohibit drugmakers from dispensing information that might be relevant to those ­off-label uses. “In fact, it’s almost irresponsible not to let them dispense that information as long as it’s truthful, accurate and not misleading,” he said.

Pitts and others say it is unreasonable to expect drug manufacturers to embark on additional clinical trials to demonstrate the safety and efficacy of already approved drugs for new purposes. That effort, like the original process, could cost drugmakers hundreds of millions of dollars in new testing and take years.

“If your drug is approved for X, why would you ever commit millions in additional testing to get approval for Y, when it’s already legal to use it for Y?” Pitts said.

Undermining the process?

The answer, according to opponents of loosening the restrictions, is public safety. If the FDA didn’t approve a drug for off-label uses, they say, that means the drugmaker hasn’t produced evidence to demonstrate the drug is safe and effective for those other uses.

“If you take it as your premise that an objective approval by someone with no financial interest is necessary to protect patients, then marketing a drug for unapproved uses is the same as marketing an unapproved drug,” said Allison Zieve, director of the litigation group at Public Citizen, a consumer watchdog group that opposes loosening the communication restrictions. To allow drugmakers to do so, she said, would undermine the whole system of FDA drug approval.

Zieve and other opponents point out that the limitations do not prevent the manufacturers from sharing peer-reviewed, scientific articles about off-label uses of their drugs with doctors and others. They just can’t promote off-label use in their marketing.

The Goldwater Institute — named for Barry Goldwater, who was a U.S. senator from Arizona — wrote the model law upon which the Arizona legislation was based. “It just seemed to me that this was a way to give physicians more information to help them treat their patients,” said Phil Lovas, a Republican who sponsored the bill while he was a member of the Arizona legislature.

The pharmaceutical industry did not formally lobby on behalf of the bill, although it has called for a revision in the FDA policies on communications about off-label uses.

Some critics say the Arizona law is meaningless because states cannot preempt federal law and because they don’t believe pharmaceutical companies will promote off-label uses unless given more direction from either the FDA, Congress or higher courts.

But the Goldwater Institute insists the federal law prohibiting drugmakers from promoting off-label use is unconstitutional. The group points to two rulings, one in 2012 and the other in 2015, in which federal courts in New York found that the FDA restriction violated the free-speech provisions of the First Amendment.

The Goldwater Institute also was behind another recent issue involving prescription drugs: what is called the “right-to-try” laws that give desperately ill patients the opportunity to receive promising experimental drugs that do not yet have FDA approval. Since 2014, 37 states have adopted right-to-try legislation, although critics too said at the time that those laws didn’t supersede federal law, which sharply restricts the dissemination of experimental drugs.

But the state laws did create momentum, which may have contributed to passage of a right-to-try bill in the U.S. Senate this summer. “I firmly believe state activity with right-to-try pushed it forward at the federal level,” said Lovas, who left the Arizona legislature in the spring to take a position in the Trump administration. “I’d like to see the same thing happen with this.”

It might. U.S. Reps. H. Morgan Griffith of Virginia and Brett Guthrie of Kentucky, both Republicans, filed separate bills this spring to ease the flow of information on off-label drugs. The House held a hearing on the bills in July but has taken no action since.  Read More & Comment...

Complex Generics Simplified ... Sort of

10/02/2017 12:46 PM | Peter Pitts

Per FDA Commissioner Scott Gottlieb:

Complex drugs comprise high cost medicines like metered dose inhalers used to treat asthma, as well as some costly injectable drugs. These medicines generally have at least one feature that makes them harder to “genericize” under our traditional approaches. As a consequence, these drugs can face less competition. In some cases, costly, branded drugs that are complex drugs have lost their exclusivity, but are subject to no generic competition.

When considering the scope of complex drugs, people often first think of drug products where the active ingredient itself is complex. Glatiramer acetate injection, a drug used in the treatment of multiple sclerosis, is a good example. However, the terms “complex drug product” and “complex generic drug” are used to refer to a much larger and diverse group of drug products. In addition to drug products with complex active ingredients, or sites of action, complex drug products also include complex drug-device combination products.

Together, this diverse collection of drug products has one or more elements that are more complex than an average drug product. This complexity, in turn, means that the scientific and regulatory pathways for approval of generic versions of these drug products are not as well traveled by generic drug developers. In some cases, use of another established regulatory pathway may be appropriate to streamline development.

Bioequivalence for complex generic drugs can be challenging with complex drug products that can’t be easily measured in the blood, or when the drug’s therapeutic effect is delivered locally to a particular organ, rather than systemically, through the bloodstream.  In other instances, showing active ingredient sameness can be challenging when the drug product contains an active mixture of components and not a single active molecule.

We recognize these problems and are taking a number of new steps to support the development of high quality ANDAs for complex generic drugs.

First, FDA is issuing a draft guidance to assist ANDA applicants and prospective ANDA applicants in creating and submitting pre-ANDA meeting requests, including meeting package materials, so FDA can give better advice to sponsors looking to develop complex generic drugs.

The guidance provides information on requesting and conducting product development meetings, pre-submission meetings, and mid-review cycle meetings with FDA. These meetings will allow for enhanced communication between generic drug applicants and FDA early in the generic drug development process, allowing for more efficient generic drug development, review, and approval pathways. We’ve found from analyzing our new drug program, that early and better meetings between FDA and sponsors can improve development timelines. We want to bring these same types of opportunities to developers of complex generics.

Second, we’re issuing a draft guidance  to help applicants determine when submission of ANDAs for certain complex products, known as peptides, would be appropriate. Peptides are compounds made up of 40 or fewer amino acids, the building blocks of proteins. There are a number of branded medicines that are peptides, where exclusivity has lapsed, but these drugs face little or no competition. This new guidance applies to ANDAs for certain specific synthetic peptides, namely, glucagon, liraglutide, nesiritide, teriparatide, and teduglutide, that reference brand-name versions of these peptides manufactured using recombinant DNA technology.

We’re doing all of this without sacrificing the scientific rigor of the process one bit. A central aspect of our approach, and our efforts to spur innovation and generic competition, is focused on adopting more rigorous and sophisticated science, including sophisticated quantitative methods and computational modeling, in drug development, evaluation, and review.

We’ll soon release other important policies aimed at spurring competition to complex drugs. But we know that better guidance isn’t the only answer. Some drugs lack generic competition because they cannot be measured through traditional in vivo bioequivalence methods and there’s no efficient and convincing bioequivalence test method available.

In these instances, an applicant needs to conduct more extensive clinical endpoint testing to show bioequivalence of a generic drug to a brand-name drug. This can be burdensome and discourage generic product development. A further barrier to generic competition for certain complex drug products is the lack of established methods for showing the sameness of the active ingredient of a proposed generic drug to a brand-name drug for certain complex drugs.

Over the next year, FDA’s generic drug regulatory science program will work to identify gaps in the science and develop more tools, methods, and efficient alternatives to clinical endpoint testing, where feasible. To help with this task, we’re holding a series of important scientific workshops, beginning today, that will identify opportunities for complex generic drug development, discuss quantitative modeling approaches and principles and aid product-specific guidance development. The workshops will also help in the development of new analytical tools that will help overcome the unique development and regulatory challenges for demonstrating active ingredient sameness in complex products. We intend for these efforts to speed product development, reduce development costs, and improve access to these products.

Scott's full announcement can be found here.
   Read More & Comment...

Qui cum canibus concumbunt cum pulicibus surgent

09/21/2017 10:26 AM | Peter Pitts

Lay down with dogs, wake up with fleas.

Now replace “dogs” with Prescription Benefit Managers” and “fleas” with lawsuits and you’ve got a pretty good idea of what’s driving the Pfizer/Johnson & Johnson story. But there’s more to it than money.

Really.

In brief, Pfizer has filed a complaint against Johnson & Johnson, claiming J&J was taking anticompetitive steps to block the sale of Pfizer’s drug Inflectra. 

(Inflectra is Pfizer's version of J&J's blockbuster drug Remicade — which treats autoimmune diseases like rheumatoid arthritis and Crohn's disease. Approved in 1998, it generated $4.8 billion in sales for J&J. Pfizer and its partner Celltrion got its biosimilar version of Remicade, called Inflectra, approved in April 2016. The two drugs are both versions of infliximab.)

At launch, Pfizer priced Inflectra at a 15% discount to Remicade's list price of $1,113 a vial.  That’s the idea behind biosimilars right, safety, efficacy – and competition to drive down costs. Keep reading.

Per Pfizer’s lawsuit, Remicade still retains 96% of the market. Pfizer’s assertion is that’s because of contracts between J&J and health insurers that require Remicade — as opposed to Inflectra — to be used first before trying other treatments for new patients.

Anti-competitive? That’s for the court to decide. But should insurers be able to block patient access for profit-driven purposes– by contract? Optimizing best practice is one thing. Venality is something else.

Wait, it gets worse. As part of the J&J contract, insurers had to commit to not reimbursing for Inflectra. And since insurers won't cover Inflectra, hospitals (according to Pfizer) don't want to keep it in stock.

Anti-competitive? Per Pfizer, “… due to J&J’s exclusionary conduct, competition has been foreclosed. J&J maintains its monopoly and has continued to capture over 96 percent of infliximab sales even while maintaining prices far above competitive levels."

Inflectra originally came out at 15% discount to Remicade but Pfizer has cut the price as the market has changed. A Pfizer spokesman said last week that the product is now priced at a 35% discount to Remicade’s wholesale acquisition cost. Also the Average Sales Price (ASP --the net price) for Inflectra and Remicade are trending in opposite directions, since launch of Inflectra ASP for Remicade has gone up while ASP for Inflectra is trending down.

As we debate drug pricing, consider this, CMS could save $140 million annually if most of their eligible patients used Inflectra rather than Remicade. It’s important to note that Inflectra has been not been approved as interchangeable with Remicade, but it does not mean (in a regulatory sense) that one product is in any way superior (in a therapeutic sense) to the other. So, why are payers so willing to block the less expensive, clinically equivalent product for new patients? The answer seems to be … because insurers can make more money by effectively maintaining a Remicade monopoly.

Is an insurer-driven monopoly good for patients? Will it lower the co-pay or co-insurance for a single patient? Sadly, these are rhetorical questions.
Is it sounding anti-competitive yet? What about anti-patient? At a time when we are debating both the price and the value of medicines, what’s wrong with this picture?

Here’s what Dominic Caruso, Johnson & Johnson’s Chief Financial Officer said at the Morgan Stanley Healthcare Conference on September 13th:

“ … relatively speaking, the economic incentive is small because the biosimilars … indicated 35% off list. And with Remicade being in the market already for many, many, many years, the way rebates go in the pharmaceutical market, we’re already there.”

But, in terms of “doing the right thing,” is “there” where we really want to be?

J&J’s response to the Pfizer lawsuit, "We are effectively competing on value and price and to date.”

But how do you “compete” if you don’t allow the other team on the field?

At the end of the day, the most important question is, will this lawsuit help or hurt patients? In the long term it will help if it reveals the venality of a rebate-driven reimbursement system. That way we can aggressively (and a lot more honestly) commence the conversation about pricing medicines based on real world value.

Oyez, Oyez.  Read More & Comment...

War Against the Orphans

09/20/2017 01:29 PM |

Great piece in the Weekly Standard by former HHS General Counsel Mike Astrue about the well-organized war against people with rare diseases.  What Mike doesn't note is that the war is being financed largely by the Laura and John Arnold Foundation.   More on this connection after Rosh Hashana.    Read More & Comment...