By Carolyn Johnson, The Washington Post

July 8, 2015

The bill slated to land on the House floor on Thursday seems unassailable on its face – the 21st Century Cures legislation promises to modernize medicine and speed the development of lifesaving treatments.

But a vocal chorus of physicians and pharmaceutical industry watchdogs warn that the bill is full of stealth provisions that could actually put sick people in harm’s way, by speeding the development of treatments that are neither safe nor effective.

It’s not exactly easy to oppose a widely-supported bipartisan bill that is often referred to as just “Cures.” But opponents say the proposed law is full of flaws, starting with its name and its key premise: that bottlenecks in the regulatory process are a big reason we haven’t cured cancer, Alzheimer’s, and a panoply of rare diseases.

To drug companies and patient advocates, expedited access to drugs and devices might seem like a huge boon. But critics are worried that the law will relax America’s standards for evaluating new drugs and devices, which are approved based on careful review of evidence — including rigorously designed clinical trials. The bill offers up a slew of new ways to evaluate drugs: for example, allowing antibiotics to be approved based on what would today be considered preliminary evidence — animal and test tube studies and very small trials in people. New medical devices could be approved based on “case histories” — potentially of just a handful of patients.

“The irony is calling this 21st Century Cures, when they’re talking about standards that were left behind in the 20th century, because they were found to not be good,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit, non-partisan think tank that does not accept money from drug or medical device companies.

Here are a few of the provisions that have sparked debate:

-The bill would allow antibiotics to be approved based on laboratory and animal tests and small, early clinical trials.

-The bill allows companies to seek expedited drug approval based on so-called “surrogate endpoints” — early indicators that a drug is working, such as whether a tumor has stopped growing in cancer.

A study published last month in the journal JAMA Internal Medicine found that efforts to expedite cancer drug approval by using such criteria has resulted in the approval of many cancer drugs that do not extend life, but do have side effects.

-The bill also threatens disclosure requirements that are intended to limit pharmaceutical companies’ influence on physicians. The bill would allow physicians to receive speaking fees and gifts from companies without disclosing them, as long as they were for medical education.

Read full story here.

By Lisa Gillespie, USA Today (Kaiser Health News)

June 7, 2015

Advocates for children with rare diseases are watching closely a congressional effort to streamline the nation’s drug approval process because the bill includes a provision that would extend a federal program that rewards companies making remedies for these young patients.

The reward program, the advocates say, offers hope to families that often have very few options. Approximately 15 million children are diagnosed with rare diseases, and 35% of deaths in the first year of life are caused by them.

“Treatments aren’t getting to kids, and kids deserve more than the leftovers,” said Nancy Goodman, the founder and executive director of the advocacy group Kids v Cancer. Goodman’s 10-year-old son died from brain cancer. She helped push for the original reward program in the hope that children like her son would have access to a wider range of treatments.

The extension of that program is part of the bipartisan 21st Century Cures bill, which seeks to rewrite the rules for drug development to make innovative treatments available faster. The overall bill has generated support on Capitol Hill, but some critics contend that it has the potential to undermine drug safety and to profit drugmakers.

Children’s advocates say there is a shortage of good therapies for rare and often deadly pediatric diseases that can include a wide variety of conditions including cancer, skull deformities or enzyme deficiencies. Pharmaceutical companies have historically been hesitant to test drugs for children because of concerns about potential negative outcomes, children’s ability to consent to treatment and the perception that the market for these drugs was limited. So doctors have often been left to try adult-tested drugs on sick children but without the studies that show pediatric safety or effectiveness. But drugs used on adults don’t always work on children in the same way because of differences in metabolism and maturation of organs.

The advocates say more research needs to be conducted with children. But that testing is a sensitive process. It can be very costly and it requires extra care because there are more stringent ethical protocols to protect these minors, who can’t often give informed consent. Bad results — either injuries or deaths — can set back research efforts and have financial consequences for the company.

With that in mind, Congress in 2011 set up a program to help promote more pediatric drug research. It gives creators of medicine for rare pediatric diseases a voucher that they can use to have another one of their drugs approved quicker than usual — six months vs. a process that can run a year or often more.

Drugmakers can also sell that voucher, which can be a big windfall for a small drug company trying to recoup research and development costs. There have been four vouchers given out since 2014, and one was sold for $67.5 million and a second for $125 million.

The voucher program, which advocates say holds big potential, expires next year. The cures bill seeks to extend it another three years.

“A lot of companies are reluctant to get into pediatric drug development because it’s very difficult if something goes really wrong,” said Alexander Gaffney of the Regulatory Affairs Professionals Society, an association for people involved in overseeing health care or the quality of health care products.

Drugs that are approved for cancer in adults are commonly not approved in kids. “Children are not simply small adults, they metabolize drugs very differently,” Gaffney said.

Critics say that however well-intentioned the voucher program is, it could have some unintended consequences. For example, a company could get a drug approved by theFood and Drug Administration but never bring it to market, if the maker decides it would not generate enough money. Yet the company would still pocket the priority review voucher.

Because of the speed sought by the program, vouchers could be given out without some of the safeguards that come in more traditional testing. For example, the research might not uncover that the drug could be fatal to a child after a few months or years.

Diana Zuckerman, president of the National Center for Health Research, a non-profit group that seeks to represent children and families on health research policy issues, says the rush in moving drugs through the system can obscure problems. Drugmakers “shouldn’t be able to sell it [or use it] unless it works,” she said.

She noted that in some studies as few as 10 kids are included because the disease is so rare. With such a small population size, the company is not likely looking at big profits.

“When you’re doing a study of rare disease, it’s a small sample size and it’s easy to manipulate the data to make it look better than it is,” said. “You don’t want an incentive to represent the company wrongly in the short term,” to get the voucher for another larger drug.

Julia Jenkins, executive director of the EveryLife Foundation for Rare Diseases, an advocacy group pushing for drug companies to spend more on drug development, wants the pediatric drug voucher program extended. She notes that the program is still too new for officials to evaluate whether it is effective.

One problematic part of the current House version, she said, is that it only extends the program for three years, and drug companies generally need 10 years to scratch up investors and research a new drug. The potential reward of expedited drug review might not be enough to allow a company to make a financial plan for a drug based on the program.

The expanded bill covers more than 60 health issues, including a $10 billion boost in funding for the National Institutes of Health and $550 million in extra money for the FDA over the next five years. Other provisions include creating a database of genomic information from a million U.S. patient volunteers and allowing the FDA to approve drugs without the gold-standard clinical trial, instead using smaller observational studies or clinical experiences.

The bill passed the House Energy and Commerce Committee unanimously in May and is expected to come up for a vote in the full House. Senators are in the early stages of working on a similar bill.

See original article here.

By Ed Silverman. The Wall Street Journal. Published Feb. 5, 2015.

Link to original article here. 

Has the other shoe dropped?

Following mounting speculation, FDA commissioner Margaret Hamburg has told staffers that she will step down at the end of March, after a nearly six-year run heading the agency. The news comes just 10 days after the FDA hired Robert Califf, a widely regarded Duke University cardiologist, as deputy commissioner for medical products and tobacco.

That move quickly set off speculation that Califf would, in fact, soon succeed Hamburg, since he starts his new job later this month. And his new job involves overseeing a large swath of the agency – the FDA’s Center for Drug Evaluation and Research; the Center for Biologics Evaluation and Research; the Center for Devices and Radiological Health, and the Center for Tobacco Products.

An FDA spokeswoman declined to say whether a search was under way or, if so, how long the process may take. For now, FDA chief scientist Stephen Ostroff will temporarily assume command until a new commissioner receives congressional approval.

Hamburg, who has been one of the longest-serving FDA commissioners, presided over a string of accomplishments and controversies. A key mission from the start of her tenure was to bolster drug safety. There had been scandals over undisclosed side effect data for such medicines as the Vioxx painkiller and contaminated heparin that was imported from China and blamed for 81 deaths.

“It’s fair to say that Dr. Hamburg came to [the agency] at a time when the FDA was under a cloud,” says Peter Pitts, who was an FDA associate commissioner for external affairs before Hamburg’s arrived and is now a policy consultant to drug makers. “Whether or not the criticism the agency was receiving was fair (most of it was not) isn’t the point. Morale was low. Moral authority amongst constituents was fading.”

Despite efforts to bolster safety, Hamburg was widely criticized following an outbreak of fungal meningitis in 2012 that was traced to a compounding pharmacy and blamed for 64 deaths. Acknowledged as the worst U.S. public health crisis in decades, the FDA was accused of failing to properly oversee compounders, and Hamburg received some harsh grilling from members of Congress.

She was also chastised for her efforts to loosen rules governing conflicts of interest between industry and the outside experts who sit on FDA advisory panels. Hamburg complained that the rules – which set limits on financial ties, for instance – made it more difficult to attract qualified panelists, although she later backed away from this position. But some consumer advocates say her oversight remained lax.

“Too often, the FDA has succumbed to industry and political pressures, implementing policies and taking actions that tilt too far toward the bottom-line interests” of industry, says Michael Carome of Public Citizen, which regularly spars with the FDA over safety issues. He argues the FDA needs a commissioner who will be an “aggressive, proactive crusader.”

There was also controversy over an FDA decision to approve an opioid painkiller, even though it did not have tamper-resistant features and an agency advisory panel recommended against approval. The FDA argued that the drug, Zohydro, offered a needed option to pain patients, but Hamburg was chastised for allegedly overstating the number of people who may have benefited.

“Under Hamburg, the FDA approved a steady stream of new opioids despite an epidemic of opioid addiction caused by overprescribing,” says Andrew Kolodny, who heads Physicians for Responsible Opioid Prescribing and argues the agency has been too friendly to industry. “I’m pleased to hear that Hamburg is leaving.”

At the same time, Hamburg won plaudits for emphasizing programs, such as breakthrough therapy designations and accelerated approvals, which have sped drugs to market faster. This remains a hot-button issue, especially among patients who clamor for treatments for hard-to-treat and rare diseases. In recent years, the number of novel new medicines that FDA has approved has steadily increased.

The issue also resonates, of course, with the pharmaceutical industry, which benefits whenever drugs are launched more quickly. “These programs have proven invaluable in bringing groundbreaking new therapies to patients more efficiently, while maintaining the FDA’s high standards for safety and efficacy,” says Jim Greenwood, who heads the BIO trade group, in a statement.

Hamburg also was caught up in a highly charged political battle. In 2011, former Health & Human Services Secretary Kathleen Sebelius overruled an FDA decision to allow the Plan B emergency contraceptive to be sold over-the-counter to younger teenagers. The FDA maintained the treatment was safe. Two years later, the FDA was able to proceed and approved its use.

Such backbone will be missed by some, especially now and Hamburg’s departure comes at an unfortunate time, according to Diana Zuckerman, who heads the National Center for Health Research, a non-profit think tank. She worries that a sweeping law Congress is drafting called 21^St Century Cures will have a detrimental effect on how medical products are regulated.

“Hamburg has been a strong voice for public health and this is a major loss at a dangerous time for the FDA,” she tells us. “The proposed legislation represents a frightening assault on the agency and the safety of medical products, and the FDA will need a strong leader to protect its public health mission.”

And in a statement, Ellen Sigal, who heads Friends of Cancer Research, a non profit, says Hamburg “changed the direction of the FDA, creating an environment of science-based collaboration that has fostered a new era of regulatory science focused on expediting the best treatments to patients.” We should note that various drug makers are among its supporters.

AND HERE IS THE MEMO THAT HAMBURG SENT TO FDA STAFF….

Dear FDA Colleagues:

It has been a privilege to serve as your FDA Commissioner for almost six years.  So it is with very mixed emotions that I write today to inform you that I plan to step down as FDA Commissioner at the end of March 2015.  As you can imagine, this decision was not easy.  My tenure leading this Agency has been the most rewarding of my career, and that is due in no small part to all of you – the dedicated and hard-working people that make up the heart of this Agency.  While there is still work ahead (and there always will be), I know that I am leaving the agency well-positioned to fulfill its responsibilities to the American public with great success.

I feel so fortunate to have worked at an organization as remarkable and productive as the FDA.  The expertise, dedication and integrity of our people and the unique nature and scope of FDA’s role make this Agency truly special.  Every day, FDA employees around the world recommit themselves to the Agency’s work, to quality science, to facilitating innovation, and to the protection of public health.  And because of your dedication and your service, we have been able to achieve so many significant milestones over the past years.

From creating a modernized food safety system that will reduce foodborne illness; advancing biomedical innovation by approving novel medical products in cutting-edge areas; and responding aggressively to the need to secure the safety of a globalized food and medical product supply chain, to taking critical steps to reduce the death and disease caused by tobacco, we have accomplished a tremendous amount in the last six years.  We can honestly say that our collective efforts have improved the health, safety and quality of life of the American people.

At the heart of all of these accomplishments is a strong commitment to science as the foundation of our regulatory decision-making and of our integrity as an Agency.  And while there are far too many significant actions, events, and initiatives to count, there are some highlights of the past years that I particularly want to mention.

In the foods area, we have taken critical actions that will improve the safety of the food Americans consume for years to come.  These include science-based standards developed to create a food safety system focused on preventing foodborne illness before it occurs, rather than responding after the fact.  We have taken several significant steps to help Americans make more informed and healthful food choices.  These include working to reduce trans fats in processed foods; more clearly defining when baked goods, pastas and other foods can be labeled “gluten free;” updating the iconic Nutrition Facts label; and, most recently, finalizing the rules to make calorie information available on chain restaurant menus and vending machines.

We have also made great strides in advancing the safety and effectiveness of medical products. Some of these important steps include new oversight of human drug compounding and provisions to help secure the drug supply chain so that we can better help protect consumers from the dangers of counterfeit, stolen, contaminated, or otherwise harmful drugs.  We are continuing to increase the speed and efficiency of medical product reviews.  We just had another strong year for novel drug approvals, with most of these drugs being approved on or before their PDUFA goal dates and most being made available to patients in the United States before they were available to patients in Europe and other parts of the world.  We launched a powerful new tool to accelerate the development and review of “breakthrough therapies,” allowing FDA to expedite development of a drug or biologic to help patients with serious or life-threatening diseases.  In fact, almost half of the novel new drugs approved in 2014 received expedited review with a combination of breakthrough designation, priority review and/or fast track status.  These included drugs for rare types of cancer, hepatitis C, type-2 diabetes and idiopathic pulmonary fibrosis, as well as a number of groundbreaking vaccines.  We have also established a regulatory pathway for biosimilar biological products that will create more options for patients.

On the medical device side, the average number of days it takes for pre-market review of a new medical device has been reduced by about one-third since 2010.  The percentage of pre-market approval (PMA) device applications that we approve annually has increased since then, after steadily decreasing each year since 2004.  We also published the Unique Device Identification (UDI) final rule that is intended to improve the tracking and safety of medical devices.  And we proposed a risk-based framework for laboratory developed tests (LDTs) to help ensure patients and providers have access to safe, accurate and reliable tests, while continuing to promote innovation of diagnostic tests to help guide treatment decisions.

We have ushered in the era of personalized medicine across all of our medical product centers. For example, many cancer drugs are increasingly used with companion diagnostic tests that can help determine whether a patient will respond to the drug based on the genetic characteristics of the patient’s tumor.  A growing percentage of our recent approvals have involved targeted therapies, offering many patients more effective response profiles and/or reduced likelihood of side effects.

We made significant progress in implementing both the letter and spirit of the Family Smoking Prevention and Tobacco Control Act.  Our tobacco compliance and enforcement program has entered into agreements with numerous state and local authorities to enforce the ban on the sale of tobacco products to children and teens; conducted close to 240,000 inspections; written more than 12,100 warning letters to retailers; proposed the extremely important foundational “deeming” rule; and broken new ground for FDA with the launch of the Agency’s first public education campaigns to prevent and reduce tobacco use among our nation’s youth.

As Commissioner, my goal has been to shape and support an FDA that is well-equipped to meet the challenges posed by scientific innovation, globalization, the increasing breadth and complexity of the products that we regulate, and our new expanding legal authorities.  I have worked hard to advocate for FDA and our unique and essential mission, including building new partnerships to support our work.  The Agency has received numerous votes of confidence with the bi-partisan enactment of a series of landmark bills extending our authority in the areas of tobacco, food safety and medical products.  In addition, we have achieved a dramatic increase in our budget, from some $2.7 billion in FY2009 to almost $4.5 billion in FY2015.

As hard as it is to leave this Agency, I am confident that the leadership team that we have in place will enable FDA to capitalize on, and improve upon, the significant advances we’ve made over the last few years.  Many of these leaders have been with the FDA throughout my tenure, and I am proud to say that we’ve recently made some wonderful new additions.

And with respect to the agency’s senior leadership team, I am pleased that Dr. Stephen Ostroff has agreed to serve as Acting Commissioner when I step down.  Since joining the Agency in 2013, and most recently serving as FDA’s Chief Scientist, Dr. Ostroff has successfully overseen numerous significant initiatives, while helping to ensure that scientific rigor, excellence and innovation are infused across the Agency.  I have every confidence that he will take on this new role with the same energy, dedication and care.

I want to extend my deepest gratitude to each and every one of you for your service and for making FDA an agency that is not only an exciting and rewarding place to work, but also a place of remarkably meaningful achievement and impact on the health and well-being of Americans.

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs