Improving Patient Advocacy Across the Globe

• 06.14.2017
• Peter Pitts

If you’re interested in the FDA’s Patient-Focused Drug Development program and attending next week’s BIO bash, hope you can attend (and participate) at this interactive panel discussion --

Improving Patient Advocacy Across the Globe

Date: Tuesday, June 20
Time: 4:15 PM – 5:15 PM
Location: Room 27 AB  

Session Description:

With the projected increase in prosperity and life expectancy in many countries over the next 20 years, the number of patients with life threatening diseases is expected to grow, presenting a range of challenges for patients, caregivers, healthcare professionals, governments and the pharmaceutical industry. As the number of patients with cancer increases, it will be important that structures are in place to support patients and their families, and to ensure that they have access to information and guidance on diagnosis, treatments and supportive care. At the same time, it will be critical to ensure that the voice of patients is included throughout the process which enables them access to innovative drugs – from input into the R&D process and all the way through public reimbursement and budget allocation decisions. The panel will focus on how strong, stable, capable patient organizations can provide a voice for those who both pay for the health system and rely on it.

Moderator:

Dr. Yoav Shechter, MSD

Panelists:

Kathleen Barnard, Save Your Skin
Peter Pitts, Center for Medicine in the Public Interest
Maria Fatima “Girlie” Garcia-Lorenzo, Philippine Alliance of Patient Organizations (PAPO)

Hope to see you in San Diego.

Regenerative Medicine Can Revitalize America!

• 06.12.2017
• Robert Goldberg

Here's an oped from the Morning Consult by regenerative medicine/stem cell pioneer and visionary Robert Hariri and me.   If America regains leadership in regenerative medicine it can spur better health and economic growth. 

Regenerative Medicine Can Help Make America Great

ROBERT HARIRI AND ROBERT GOLDBERG   |   JUNE 12, 2017 | 05:00 AM   
When President Donald Trump urged the biopharmaceutical industry to reduce the price of new medicines and to increase its manufacturing in the United States, many took it as a threat.

We believe it’s a call to action. America’s ingenuity in biomedical research is unsurpassed. However, our country is losing out to other nations in the fastest growing biotechnology sector, called regenerative medicine: harnessing the capacity of our cells to repair and restore health and sustain well-being.

Second place is not an option. The regenerative medicine market is growing about 21 percent a year and is expected to be worth over $350 billion by 2050. Today, the U.S. regenerative medicine sector is generating $3.6 billion in revenues and has produced 14,000 jobs. By 2050, the industry could create nearly a million new jobs nationwide.

Regenerative medicine will also reduce the cost of disease. Such therapies will replace drugs, devices, and surgery, saving lives, increasing productivity, and reducing the cost of care. This transformation will add trillions in value to our economy.

Finally, regenerative medicine will also make America more secure. Our nation still lacks the ability to quickly and cheaply mass produce vaccines, antidotes, and cell therapies to counter pandemics and bioterrorism. Our fighting forces need reliable sources of these countermeasures and deserve immediate access to treatments that give them back their lives. We shouldn’t outsource the safety and well-being of our nation and our Armed Forces to other countries.

To regain leadership in regenerative medicine, U.S. firms don’t need government loans, tax credits or massive de-regulation. Instead, it needs the opportunity to invest in reducing the time and cost of manufacturing cellular therapies. To the extent that regenerative medicine is curative it must be made available at vaccine like prices. At present, only a handful of people can afford such treatments.

China and Japan are now in forefront of reducing the cost of producing stem cells, tissue, and other products with restorative biological properties. As a result, they are attracting more capital and forming more new companies than the U.S.

In 2014 Japan became the first country in the world to adopt an expedited approval system specifically for regenerative medical products and to allow outsourced cell culturing. Two products were approved under the new system within a year of its adoption.

By contrast, the Food and Drug Administration regulates any use of manufactured stem cells as equally risky without regard to prior use, health benefit, or therapeutic potential. Indeed, many of the most common stem cell therapies — including bone marrow transplants and blood transfusions — would require 10 years of FDA review if they were brought to market today.

The problem isn’t over-regulation. It’s outdated regulation. Safety checks and benchmarks for cell manufacturing should be based on real world evidence of past applications. Regulation should focus on the specific potential side effects for each specific potential use. In this regard, we agree with incoming FDA Commissioner Scott Gottlieb, who has noted, “Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”

In fact, the United States has the best regenerative medicine manufacturing technology in the world. But it is literally sitting unused in warehouses.

For example, under the Accelerated Manufacture of Pharmaceuticals program, private companies partnered with the Defense Advanced Research Projects Agency to develop mobile cell and tissue manufacturing plants that can be set up almost anywhere. The facilities can produce cells and tissues at a fraction of the current cost. These mobile factories make real-time production of vaccines and biologics for potential bioterrorist threats and pandemics possible. They are also low-cost, high-tech platforms for experimental evaluation of any type of regenerative medicine.

AMPs are operating in Indonesia, Singapore, China, and Japan where cell products — including vaccines — are being mass produced. Not a single AMP is being used in the United States because of outdated regulations.

To remove this regulatory obstacle, the Trump administration should establish a separate regenerative medicine pathway. This pathway, which could be developed by DARPA, FDA, and the Centers for Disease Control and Prevention, would develop regulatory standards for the safe manufacturing and testing of development of regenerative products to treat battlefield related traumas such as traumatic brain injury, life-threatening limb damage, and drug-resistant pathogens.

The focus on the conditions and circumstances unique to war or counter-terrorism is both appropriate and strategic. After World War II, Franklin Roosevelt directed that the scientific and entrepreneurial talents used to achieve ramp up war-time production of penicillin and blood plasma “be used in the days of peace ahead for the improvement of the national health, the creation of new enterprises bringing new jobs, and the betterment of the national standard of living.”

What was created exceeded that vision. The cooperative efforts to achieve mass production of penicillin and blood plasma inspired and supported the creation of industries that employ millions of people today.

Similarly, developing an affordable source of cell therapies to heal our fighting forces and protect the homeland will yield a wide array of affordable technologies and cures that will produce, in FDR’s words, a fuller and more fruitful employment and a fuller and more fruitful life. Simply put, by making the manufacture of regenerative medicine affordable can help make America great.

 

Robert Hariri is CEO of Celularity. Robert Goldberg is vice president of Center for Medicine in the Public Interest.

Regulatory Learnings from the Real World

• 06.12.2017
• Peter Pitts

In March, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSARM). voted 18-8 that Opana ER’s benefits do not outweigh its risks. And on June 8th, the other shoe dropped.

"After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks," the agency said in announcing the move. “This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse."

The FDA said it was asking Endo to voluntarily cease marketing Opana ER. But it added that if the company refuses, the agency will "take steps to formally require its removal by withdrawing approval."

The FDA said its data indicate that the abuse of the drug has shifted from snorting to injection following reformulation in 2012, which was intended to help the pills resist physical and chemical manipulation. Subsequently, Opana ER was associated with a notorious outbreak of HIV and hepatitis C infection in rural Indiana two years ago, caused by needle-sharing among opioid addicts.

"The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in a statement. "This action will protect the public from further potential for misuse and abuse of this product."

What can we learn from this action? First, that when a product’s risk/benefit profile is carefully monitored, aggressive action can be taken in a timely manner. But should we need an outbreak of HIV/AIDS and Hep-C to sound the alarm?

Kudos to the FDA for taking appropriate action to protect the public health – but we need more. Specifically we need the agency to work with sponsors o design more and better early warning mechanisms so that a problematic product can we recalled before dire consequences ensue. That means new and more immediate ways to collect, analyze, and share real-world evidence.

It’s time for apps to take center stage in the battle against opioid abuse.
 

Managed Care Magazine Unleashes Attack on Orphans

• 06.08.2017
• Robert Goldberg

If it’s not obvious from the title “Orphan Drugs: Way Too Many, Way Too Expensive” the essence of Joseph Burns article in Managed Care Magazine is: isn’t is terrible that drug companies – who neglected rare and tropical disease for decades to make money – are now making money developing drugs for conditions they were criticized for ignoring and for which the Orphan Drug Act was created. 

Burns article is based on the material and media accounts generated by a syndicate attacking rare disease groups and the Orphan Drug Act funded by Laura and John Arnold Foundation to the tune of $22.4 million. It is a network of left-leaning think tanks with a bias against the profitability of medical innovation, news outlets and patient advocacy organization that spread the anti-orphan message far and wide.   

The Arnold funded think tanks provide the Arnold-funded news outlets with factoids and quotes attacking orphan drug development and patient groups. The Arnold funding patient organization then provides the rest of the syndicate with grass roots outlet for even more quotes and opportunities to spread the message.   The advocacy group, Patients for Affordable Medicines, is run by David Mitchell who recently retired as a founder and principal of PR firm GMMB. 

Mitchell knows a little bit about being a front organization or a pass through for political advocacy: GMMB earned $236.3 million from Hillary for America 2016 and moved over $314 million in Obama ad buys during the 2012 election cycle.  It also runs a group called Waterfront Strategies that handles soft money, consulting and ad buys for a number of PACs. 

Burns fails to tell his readers of Mitchell’s past and present work as a conduit. Instead, he depicts Mitchell as a selfless crusader against “drug companies (that) are manipulating the law that created the orphan drug status.  Mitchell claims orphan drug development is mostly  “salami slicing” strategies—companies dividing diseases into smaller and smaller categories based on genetic and biomarker differences so their products can achieve the coveted orphan drug status.”

“This gaming of the system to cut and recut for different orphan diseases means they get to use the same drug for multiple orphan drug designations,” says Mitchell. “That needs to stop.”

Neither Burns or Mitchell offer any proof that such practices are hurting patients.   Instead, their beef with the fact that companies have the audacity to attempt ot make a profit. 
Burns notes: “some commentators have said the trouble starts with the law’s prevalence-based definition of a rare disease as a condition that affects fewer than 200,000 individuals. Because drug companies can now price orphan drugs at between $100,000 to $200,000 per patient per year, they need only 5,000 to 10,000 patients to hit the blockbuster mark of $1 billion in annual sales.”

Well yeah, that’s what the Orphan Drug Act is supposed to do: Encourage the development of new medicines for groups of patients that do not benefit from existing therapies.

But Burns – like most critics past and present – claims “the law’s intended purpose of encouraging the development of drugs for rare diseases has been undermined in various ways.”

Rather than provide evidence of how the act has been undermined, Burns just asserts: companies “are using the 1983 Orphan Drug Act to secure lucrative incentives and gain monopoly control of rare disease markets where drugs often command astronomical price tags”

Burns assertions of gaming and astronomical prices are without substance:

For instance, he fails to note the retail price of the top selling 10 orphan drugs are a bargain relative to lives lost, health care spending saved and productivity gained.  

Take Revlimid (used at various stages of multiple myeloma) as an example.  The true per patient cost – net of rebates, discounts, and other concessions – is about $78K per patient.  The median charge for a hospital stay is $82000.  

Revlimid sales in 2014 were about $4.4 billion.  But extrapolation of gains in life expectancy based on previous studies of the impact of advances in myeloma care on longevity suggests that each year the use of Revlimid and other novel treatments generate $22 billion in added value. 

Further, many other orphan drugs NOT reviewed by Burns treat extremely small populations and require continuing evaluation and expensive production activities. 

Of the orphan drugs approved since 2012, the average patient population has been under 2000. Nearly 80 percent of the new products or approvals were developed by small biotech companies that are losing money.  If Burns and the critics he channels thinks that punishing companies after they turn a profit will not affect orphan drug development, they should prove it, not force dying patients into a twisted social experiment. 

In addition to being upset about the handful of profitable orphan drugs, Burns claims that slicing and dicing (as he calls it) is an unfair way to make money.  He notes: “Herceptin, originally approved as a breast cancer drug, has gained orphan designation for pancreatic and gastric cancers because those cancers can now also be classified as HER2-positive and HER2-negative.” 

Burns cites an Arnold Foundation funded Kaiser Health News ‘study’ that highlights the number of orphan drug designations generated from existing medicines.  It is not a study, it is simply the same list of orphan drug designations and approvals the FDA generates with KHN’s negative spin added as narrative. 

It is true that there has been an increase in the discovery of markers for previously untreated tumors that are certainly fatal.  And it is true that companies are conducting clinical trials or engaging in data mining to establish benefit in other subpopulations.  KHN implies this is an immoral practice because profit is involved.  

As the FDALawBlog points out, in some cases, a single orphan drug designation can result in multiple periods of orphan drug exclusivity. There appear to be a growing number of cases where FDA has granted multiple periods of orphan drug exclusivity based on the same original orphan drug designation, and where the drug’s indication evolves into something new, shedding and subsuming the previous indication statement.”

The obvious ‘solution’ to this situation is to allow companies faster approval for a broad number of tumors with biomarkers.  FDA’s recent approval of Keytruda for all solid tumors with a specific mutation clears the path for this approach.  Martin Makary (who Burns quotes) suggests this conditional path as an alternative to the multiple exclusivities.  But the anti-orphan Arnold Foundation funded Jerry Avorn and Aaron Kesselheim has attacked the use of biomarkers as a watering down of science pushed by pharma funded patient groups. So my guess is that find a way to characterize THAT as profiteering.  Indeed, Kesselheim is behind the Arnold-funded effort to eliminate biomarker-based disease treatment from Orphan Drug Act designations. 

Burns and the anti-orphan movement suggest instead that orphan drug patent life should be shortened to allow for more generics. But that begs the question: as orphan drugs have gone generic, why haven’t the companies used their first to market exclusivity to engage in similar research?  If it is just slicing and dicing, why wouldn’t a generic company want a line extension?

The answer is supplemental approvals of any type require time and money that innovator companies invest and generics don’t. The FDA does not simply tack on additional patent life.  To obtain a period of orphan drug exclusivity for a drug that is otherwise the “same drug” as a previously approved drug (i.e., a drug containing the same active moiety and that is for the same orphan disease or condition), the sponsor must demonstrate that its product is clinically superior (by showing greater efficacy, greater safety, or by providing a major contribution to patient care) to the previously approved drug.” 

If Burns and the “experts” he quotes wants to repurpose generic Gleevec or Humira for an orphan use and not charge for it, they should set up a company and do so.  

Indeed, Burns and every other critic he cites in his repetition of how the ODA is used to make money ignores a very important point: “Generic competition is generally not thwarted because of the ability of an ANDA applicant to carve-out of its labeling (and thus avoid) a period of unexpired orphan drug exclusivity on the brand-name Reference Listed Drug.” 

The FDA can approve a generic version of the drug product for one or more uses even if, in the future, an innovator company develops another use that garners orphan drug exclusivity. 

Which means the generic version of the drug is on the market and can be used off-label.  

But the anti-orphan critics attack off-label use as a slick, often illegal way, of increasing sales. So that leaves people with rare diseases with a longer wait for medicines that would cost more to make and must rely on generic companies to invest in new indications once innovator drugs go off patent. 

I know people with rare diseases can’t live with that.  I wonder if Joseph Burns and the anti-orphan movement can. 

The economics of opioids

• 06.08.2017
• Peter Pitts

The Joint Economic Committee (JEC) will hold a hearing on June 8th to explore the economic aspects of the opioid crisis.

According to the JEC website, “The opioid problem has various elements on the demand and the supply side that JEC witnesses, Professor Sir Angus Deaton, 2015 Nobel Prize laureate in economics, Ohio Attorney General Mike DeWine, Dr. Lisa Sacco, Congressional Research Service Crime Policy Analyst, and Dr. Richard G. Frank, Professor of Health Economics at Harvard will address in detail.” Mike DeWine? Really?

We’ll see.

I suspect that a key aspect of “opioid economics” that will get very little attention is the unwillingness of PBMs to pay for opioids of the abuse-deterrent variety. That’s simple economics. The reason that there are nearly a quarter of a billion generic, non-abuse opioid tablets prescribed annually (vs. about 5 million abuse-deterrent ones) is because they are inexpensive. But that is a failed metric. It’s benefited the bottom line of PBMs and created a national epidemic.

The same math explains why PBMs often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy even though there are FDA-approved, non-opioid medicines specifically designed and labeled to treat these conditions.

We’ll see.

Zero-sum thinking is an obsession of mine, but mostly in economics. -- P. J. O'Rourke

Single Payer. All the news that's fit to print?

• 06.04.2017
• Peter Pitts

To the Editor:

Per, "The Single-Payer Party? Democrats Shift Left on Health Care," (NYT, June 3, 2017) it seems somewhat ham-handed to have only one paragraph, deep inside the page 16 jump of a Page One article, mentioning the enormous cost and tax consequences of the California legislation -- and no mention at all of the proposal's impact on patient choice and resource rationing. That's not fake news -- but it certainly isn't all the news that's fit to print.

Peter J. Pitts
 

Let's partner with Canada to fight opioid abuse

• 05.30.2017
• Peter Pitts

Per FDA Commissioner Scott Gottlieb, “As Commissioner, my highest initial priority is to take immediate steps to reduce the scope of the epidemic of opioid addiction. I believe the Food and Drug Administration continues to have an important role to play in addressing this crisis, particularly when it comes to reducing the number of new cases of addiction.”

One place to look for smart policy solutions is just north of the border, where medical experts and public health officials in Canada are also concerned about the abuse of prescription opioids. A study published by the Canadian Health Policy Institute (CHPI) estimates that if all prescription opioids in Canada were abuse deterrent formulations, societal costs could be substantially reduced.

“Mandating abuse deterrent formulations for prescription opioids could reduce societal costs by $140 million to $4 billion annually.” 

The study estimated that the economic value of the health, social and productivity losses associated with the abuse of prescription opioids in Canada could have averaged as much as $4.3 billion per year during the four-year period from 2012 to 2015. The study also reviewed clinical research showing that existing abuse deterrent formulations ranged from 3.3% to 98.8% effective at reducing abuse rates of the tested products. The median effectiveness reducing abuse rates by between 45.1% and 64%.

The study concluded that if the federal government mandated abuse deterrent formulations for all prescription opioids, it would discourage non-medical use of these drugs, reducing associated societal costs by an estimated range of savings between $140 million and $4 billion annually.

Perhaps a cross-border partnership is in order to address this bi-lateral regulatory issue.

Trumping FDA?

• 05.25.2017
• Peter Pitts

As per a no-nonsense report in BioCentury, President Trump’s FY18 FDA budget request envisions cutting medical product safety funding by $17.8 million. The cuts would reduce the agency’s ability to ensure the safety of imported drugs and ingredients, and to conduct safety research the agency characterizes as “critical.”
FDA stated that the budget proposal would also curtail "proactive" activities to respond to global disease outbreaks.

The proposed cutbacks are a consequence of the administration’s proposal to transfer 100% of the responsibility for funding medical product reviews to user fees. Some FDA medical product safety and regulatory science activities cannot be funded with user fees.
There is almost no chance that Congress will agree to the Trump administration’s plan to rip up the user fee reauthorization agreements that FDA and industry have negotiated. It is not clear whether FDA intends to implement the medical product safety oversight cuts outlined in the budget if Congress rejects the administration’s revamped user fees.

To compensate for proposed budget cuts, the proposal said FDA will "support at lower funding levels regulated product field exams, import entry review, investigations, sample analysis, and inspections for surveillance, compliance, and follow up activities, both domestically and abroad." The proposal added: "Risk assessments will be impacted along with sharing information with regulatory partners."
The proposed $11 million cut to the Center for Drug Evaluation and Research (CDER) medical product safety budget would require the center to “reprioritize and refocus how it promotes and protects public health,” the document said.

The cuts would include "some contracts that promote drug safety and research studies, investments in innovation and research, and training and development opportunities for personnel,” it said. The document said FDA will seek “to minimize the impact of these reductions on FDA‘s core mission activities.”
The medical product safety budget at the Center for Biologics Evaluation and Research (CBER) would be cut by $7.5 million. CBER would "reduce its applied scientific research, which supports the development of innovative products, in order to preserve critical regulatory oversight of its non-user fee programs that address blood components, tissues, and allergenic products." Spending on equipment upgrades and maintenance would be cut, as would "the number of research fellows hired to support the regulatory science program.”

The proposal noted that “research fellows bring innovative ideas, talents, and skills to FDA.”
The budget proposal included reductions in CBER’s “work on the development of laboratory standards, including reference materials, assays, and methodologies that improve product quality and provide standards and guidance to address new technologies and emerging diseases.”
If Trump’s budget is enacted, CBER would "reduce staff through attrition in its non-user fee activities that include the regulation of blood components, tissues, and allergenic products.”

CBER would be forced to “reprioritize how it provides advice to sponsors and reduce resources dedicated to the review of blood components for transfusion and allergenic extracts as well as the ability to provide advice to sponsors of tissues that do not require premarket review.”

As a result, CBER "may no longer be able to exceed its performance target to complete review and action on 90% of complete blood bank and source plasma Biologic License Application supplements within 12 months after submission date.” 
In addition, CBER would “limit proactive work to respond to infectious disease outbreaks globally, including limiting its active participation in international collaboration activities.”

More to come on this.

Off-Label Use: TIme Marches On

• 05.20.2017
• Peter Pitts

In a recent Washington Post op-ed, Bill Schultz, the former deputy commissioner for policy of the Food and Drug Administration during the Clinton administration, incredulously offers that FDA policies developed 50 years ago are good enough for life in the 21st century (Trump’s new FDA commissioner has a huge decision to make). He’s wrong.

Time marches on and regulatory practices must evolve to better serve the public health. Nowhere is this more urgent than in making sure physicians and patients have unencumbered access to truthful accurate and non-misleading information about FDA-approved medicines –- both on and off-label. In a draft guidance, FDA notes that ‘‘good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.’’ And, according to the House Energy & Commerce Committee’s 21st Century Cures Initiative, “… conversations between and among doctors, patients, researchers, and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients.”

Off-label communications is about getting the right medicine to the right patient in the right dose at the right time.  Off-label communications advances both the practice of medicine and the safe and effective use of medicines.

No HELP

• 05.09.2017
• Peter Pitts

It’s disappointing to say the least when our fine elected representatives place scoring transient political points in front of advancing the public health.

Such is always the case with the perennial non-starter issue of drug importation. What makes it even more dangerous this time is how it could delay swift and clean PDUFA approval.

Front and center is Senator Bernie Sanders. His two PDUFA amendments won’t lower drug prices or increase access for any Americans. But they would negatively impact safety and undercut intellectual property protection.

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.

So just what is Senator Sanders trying to accomplish? Certainly not a clean PDUFA – which is just what the doctor ordered for the FDA’s Gottlieb Era reforms -- including programs to help lower drig prices by expediting single sourcwe generic reviews.

He certainly doesn’t seem to be interested in safety concerns. Or counterfeits. Or cold-chain control. Or even that every study by the Congressional Budget Office reiterates over and over again that such schemes don’t save the American consumer any money.

But is sure is good for headlines. For shame.