Thursday, 29 September 2016

A Golden Ticket That Fast-Tracks A Drug Through The FDA

Drugmaker Sarepta Therapeutics won a big victory when its $300,000 muscular dystrophy drug was recently approved, but the company had other reasons to celebrate, too.

They were also awarded the drug world's equivalent of a Willy Wonka golden ticket.

The ticket, known as a rare pediatric disease priority review voucher, is part of a program created by Congress in 2007 to encourage the development of drugs for tropical diseases and later expanded to rare pediatric disorders. Any company awarded a voucher can use it for a fast-track government review of one of its future drugs - or it can sell the voucher to another company.

“The only people who would buy a priority review voucher would be someone who had something that wouldn't merit its own priority review but they want the priority review,” says Dr. Tim Coté, a former FDA official who now runs a consulting firm for rare disease drugs.

In other words, the companies willing to pay for a voucher are most likely trying to get a medicine that treats a common disease on the market quickly for competitive reasons, he said.

“It might be a blockbuster - say a new statin,” Coté said, referring to a drug that lowers cholesterol. “A priority review would make all the difference in the world.”

A voucher guarantees a company that its drug will be reviewed within six months, as compared to the standard 10. But approval isn't assured.

And the sale of one voucher can earn hundreds of millions of dollars for a small company like Sarepta. Last year, a voucher sold for a record $350 million when AbbVie Inc. bought one from United Therapeutics. The company has not announced plans for the voucher.

It's those price tags - as well as admonishments from the Food and Drug Administration - that have some industry watchers debating whether the program should continue. The House voted Tuesday to extend the program until the end of the year, after the Senate had already done so. It was set to expire this month.

Members of Congress, the pharmaceutical industry, and rare disease advocates have passionately supported the voucher program as a way to incentivize rare disease drug development. The goal, they say, is to steer more money toward rare disease drug developers by allowing them to sell the voucher to the highest bidder. But others, such as FDA officials and academics, have questioned whether the program is leading to any new drugs for rare diseases.

Nancy Goodman, executive director of Kids v Cancer, is a champion of the bill. She created her foundation after her son died seven years ago of medulloblastoma, a rare pediatric brain cancer.

There were no drugs available for her 10-year-old son, she said.

“I believe and hope we will see a whole crop of pediatric disease drugs because of the program,” Goodman said.

The legislation extending the program passed the House and Senate by unanimous consent and awaits action by President Barack Obama, who is expected to sign it. Advocates are fighting to keep the program authorized until Dec. 21, 2018 as part of the 21st Century Cures Act, which has passed the House and has stalled in the Senate, where backers hope it will be taken up after the elections.

But officials at the FDA, which must implement the vouchers, are at odds with industry and advocates.

Dr. John Jenkins, director of the office of new drugs in the Center for Drug Evaluation and Research at the FDA, has said he supports the overall goal of providing incentives to promote drug development but that the voucher program is wrong.

In December, Jenkins told a reporter at the industry publication Pharmaceutical Executive that vouchers raise safety concerns because the program requires the FDA to give any drug accelerated review - even when reviewers have to address complex issues.

“We're not making pizza here,” he said.

Jenkins declined interview requests for this story. FDA spokeswoman Sandy Walsh said, the “FDA has not seen evidence that the program is effective.”

Walsh also said the agency is concerned that the voucher program “adversely affects the agency's ability to set its public health priorities” and “the additional workload from the program strains the agency's resources.”

The voucher program does require companies to pay a user fee of nearly $3 million to help the agency pay for the program. But the additional money may not be sufficient.

In March, a Government Accountability Office report said FDA officials complain there is too little time to use the money to hire and train additional employees to do accelerated reviews and that the one-time fee does not enable hiring of long-term staff.

The GAO's report said it was too early to say whether the pediatric priority review voucher program, approved in 2012, is stimulating development of drugs.

Of the seven pediatric review vouchers that have been awarded, four have been sold to other drug companies.

Drugmaker Sanofi has redeemed two of the vouchers. For the first, they paid $67.5 million and used it to expedite review of their cholesterol drug Praluent. Later, Sanofi spent $245 million for a voucher and said in February it would be used to speed up the FDA's decision on a new type 2 diabetes treatment.

If a voucher is not used, it can be sold an unlimited number of times before being used.

Sarepta plans to sell its voucher, Chief Financial Officer Sandy Mahatme told Wall Street analysts in announcing approval of its drug to treat Duchenne muscular dystrophy. He said the money would help finance other drugs in its pipeline, pay for the scaling up of its manufacturing and support the company's entry into European markets.

Mahatme said they have already reached out to “a bunch of potential buyers.”

KHN's coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

Tuesday, 27 September 2016

When Drug Reviewers Leave The FDA, They Often Work For Pharma

More than a quarter of the Food and Drug Administration employees who approved cancer and hematology drugs from 2001 through 2010 left the agency and now work or consult for pharmaceutical companies, according to research published by a prominent medical journal Tuesday.

Dr. Vinay Prasad, a hematologist-oncologist and assistant professor at Oregon Health and Science University, sought to understand the so-called “revolving door” between the FDA and the pharmaceutical industry, which he said is often discussed but hadn't been quantified.

“We all know about these anecdotal cases” of a person who was  “often a major player at the FDA, someone in an important role - and then they leave the FDA and go and work for industry,” Prasad said, but he couldn't find anyone who knew whether this happened “5 percent or 60 percent” of the time.

Prasad and his colleague Dr. Jeffrey Bien, an internal medicine resident also at Oregon Health, tracked 55 FDA reviewers in the hematology-oncology field from 2001 through 2010, using LinkedIn, PubMed and other publicly available job data. They found that of the 26 reviewers who left the FDA during this period, 15 of them, or 57 percent, later worked or consulted for the biopharmaceutical industry. Put another way, about 27 percent of the total number of reviewers left their federal oversight posts to work for the industry they previously regulated. They published their findings in The BMJ as a research letter.

Going to work for industry after leaving the FDA is not inherently bad, but it does raise some questions.

“If you know in the back of your mind that your career goal may be to someday work on the other side of the table, I wonder whether that changes the way you regulate,” Prasad said. “Are you more likely to give [companies] the benefit of the doubt? Are you less likely to beat them up hard over [using bad comparisons in drug studies]?”

Prasad focused his research on his own field - hematology-oncology - because it spawns a large number of new drugs and reviewers have a lot of autonomy, he said.

“There's a lot of room for interpretation in deciding whether or not a cancer drug should be approved,” he said, because so many studies of cancer drugs rely on what's called a “surrogate endpoint,” meaning that something other than survival or quality of life was measured to determine whether a drug worked. For example, shrinking a tumor may be a stand-in for survival. But according to one of Prasad's previous studies, there isn't always evidence that surrogate endpoints are linked to better health outcomes, suggesting that some approved drugs aren't as beneficial as they appear.

“Sometimes, the public needs [the FDA reviewers] to be firm. If they're not, no one else in the health care sector is going to be,” Prasad said, adding that once the agency approves a drug, the Centers for Medicare & Medicaid Services has to cover it and can't negotiate prices under current laws. “The FDA is often the only real wall between ineffective, harmful drugs and patients.”

He and Brien tracked reviewers instead of higher ranking officials because reviewers provided a larger sample size, Prasad said. They would have liked to include reviewers named on denials as well, but the denial documents are secret, making it impossible to identify the reviewers.

Although Prasad said FDA reviewers have a lot of power over approvals, Dr. Joshua Sharfstein, the FDA's principal deputy commissioner until 2011, disagreed.

“There are just so many checks and balances within the review process that it's really not up to one person by and large,” said Sharfstein, now an associate dean at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Key regulatory decisions are looked at from many different angles. I think it would be very difficult for an individual to do something inappropriate and not have that caught.”

Sharfstein said he has met with companies to offer advice, but was not compensated for it.

The revolving door is a fair topic to study, he said, but having former FDA officials on the pharmaceutical industry payroll can have a public health benefit. Former FDA employees with deep knowledge of the approval process help make it go smoother by ensuring all the relevant research is complete and the latest pathways to approval are understood.

“Companies are very nervous about the FDA,” he said. “So they need to have an understanding of how the FDA works.”

FDA spokesman Jason Young said employees leave the government to work for industry at various agencies, not just the FDA.

“The FDA has a strong set of rules in place to ensure that our employees are working in the public interest, not to advantage any company, organization or individual,” he said, adding that these include protecting confidential information they learned at the FDA and a “cooling-off” requirement for senior officials before they can work for industry.

Former FDA Chief Dr. Margaret Hamburg, who left the administration last year, told Stat News in March that she would wait before jumping into an industry job, adding that “this perception of the revolving door is damaging to everyone” and that she would not consider “any boards of any company big or small that was regulated by the FDA for a couple of years.” She also is quoted as saying it is “unfortunate” that people think “a complete division” is necessary between the agency and the industry.

The FDA Alumni Association, whose slogan is “serving those who have served,” currently lists four job openings for former FDA employees. Three are at consulting firms and one is at a law firm seeking an “FDA compliance paralegal.” Of the consulting jobs posted, one is for a regulatory scientist and the other is for a regulatory toxicologist. The third is a food and cosmetic consulting job.

KHN's coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

Viewpoints: House Calls - A Better Idea Than Ever; Is The FDA Tightening Hold On Generics?

A selection of opinions on health care from around the country.

Tuesday, 13 September 2016

Monday, 12 September 2016

Study: Health Spending Related To Opioid Treatment Rose More Than 1,300 Percent

The nation's ongoing opioid problem comes with staggering physical and emotional costs to patients and families. But the dollar cost to the health system has been harder to peg. Now a new report shows a more than 1,300 percent rise in spending by health insurers in a four-year period on patients with a diagnosis of opioid dependence or abuse.

From 2011 to 2015, insurers' payments to hospitals, laboratories, treatment centers and other medical providers for these patients grew from $32 million to $446 million - a 1,375 percent increase.

While that's a small portion of the overall spending on medical care in the United States, the rapid rise is cause for concern, says Robin Gelburd, president of Fair Health, a nonprofit databank that provides cost information to the health industry and consumers.

“That really shows the stress on the health system and the impact on the individuals,” said Gelburd.

The Fair Health study found a sharp difference in how much insurers spend on individual patients with such a diagnosis.

On average, insurers spend $3,435 a year on an individual patient, but for those with an opioid dependence or abuse diagnosis, that amount jumps to $19,333. Those numbers reflect what insurers actually paid. The report also includes data on what providers charged, amounts that are lowered by their contracts with insurers.

The study, set to be released Tuesday, builds on one Fair Health released in early August that found a 3,000 percent increase in the volume of insurance claims related to opioid dependence diagnoses between 2007 and 2014.

The latest study - part of a series - offers amounts associated with claims billed by providers and paid by insurers for the types of medical services used.

Both studies use de-identified claims data from insurers representing more than 150 million insured Americans who either have insurance through work or buy coverage on their own.

There have been other efforts by several researchers to quantify the cost of the opioid problem on the overall economy, estimated in the tens of billions of dollars.

The new report adds to the available data “that it's not just the human cost associated with the opioid crisis that is enormous, but also that the economic costs are staggering,” said Dr. Andrew Kolodny, senior scientist at Brandeis University. He did not work on the study.

Prescription drugs are shown.The surge in spending on patients with opioid diagnoses is likely a combination of factors, the report notes. As media attention focuses on drug dependency, more people may be seeking treatment. At the same time, prescription and illegal use of narcotics may also be increasing.

The study found that emergency room visits and laboratory tests accounted for much of the spending.

Based on claims volume, the fastest-growing set of services in terms of utilization were for alcohol or drug therapy. Lab tests, including checks for barbiturate or opioid use, were not far behind.

Researchers did not use 2015 data for lab test costs, noting that a change in billing codes was made that increased the number of categories - and, in some cases, appear to generate higher payments by insurers. It is too early to estimate the long-term effects of the change, Gelburd said.

The report gives some examples of the changes, however. For example, one billing code for a test on opiate use commonly brought in a $31 payment from insurers prior to the change. The two billing codes that replaced it now are commonly paid at $78 and $156.

The new billing codes may reflect new technology in testing, said Gelburd. She said some observers speculate that the rapid increase in lab spending might reflect that, with more patients in therapy, the tests are being used to ensure they are taking their proper medications and not abusing narcotics.

But the spending might also reflect a growing use of very expensive urine and blood tests when less expensive ones would be sufficient, said Kolodny.

“I worry about profiteering,” said Kolodny. “We do need tests, but not the expensive ones. A lot of clinics are making extra money off these lab tests.”

The overall increase in spending across all types of medical services “is a societal issue,” said Gelburd, who says policymakers need to ensure that changes are made to address the problem.

“Are medical school curricula adjusting to recognize the growing need for these services? Are insurers increasing the number of providers in their networks to ensure sufficient access? Are consumers being educated? It's an issue that has to be dealt with in all quadrants.”

Thursday, 8 September 2016

Behind The EpiPen Monopoly: Lobbying Muscle, Flailing Competition, Tragic Deaths

Thirteen year-old Natalie Giorgi probably didn't know the name of the company that makes EpiPen. The 2013 death of the Sacramento girl from a peanut-induced allergy attack inspired passage of the California law that made the Mylan product a staple at every school.

It was Giorgi's story, not industry lobbying, that then-California State Senate Minority Leader Bob Huff, R-San Dimas, said inspired him to usher through the requirement that public schools in the state stock the injectors. He said he was also influenced by one of his staffers who had a child with life-threatening allergies.

“It was just sort of organic,” said Huff about carrying the bill. “It seemed like we oughta do better to protect these kids.”

Mylan, the company that raked in $1 billion last year for the EpiPen, takes credit for passing “legislation in 48 states” to ensure schools have them. But its political maneuvering is only one reason the company has, in its own words, become “the number one dispensed epinephrine auto-injector.”

High-profile deaths in several states, particularly among school-age children, have helped to spur legislative action and fuel demand for consumer-dispensed epinephrine. At the same time, no other company has been able to effectively compete with Mylan's drug-delivery device. Patent rules, and competitors' manufacturing foibles, also have helped the company reign over the consumer epinephrine market.

When someone with a severe allergy goes into anaphylactic shock and can't breathe, “seconds count,” said Mylan CEO Heather Bresch in a recent CNBC interview about the EpiPen, which now has a sticker price of $608 per 2-pack. That's why, she said, “they need to be everywhere.”

Bresch said lobbying is just one way the company has spent hundreds of millions “developing” the EpiPen since it acquired the patent in 2007.

Indeed, Mylan's presence in state houses across the country has grown exponentially. The company added lobbyists in 36 states between 2010 and 2014, according to the Center for Public Integrity, outpacing every other U.S. company. And it spent more than $1.3 million lobbying in 16 states since 2012, according to the National Institute on Money in State Politics. (Those are not the exact states that passed the school requirements, however.)

Just in the past several years, 10 states have passed laws requiring epinephrine in schools. Another 38 states have passed laws permitting them, according to the Food Allergy Research & Education advocacy group (FARE).

Nebraska appears to have been the first state with a school epinephrine requirement. High asthma rates in the state, as well as a couple of school-based child fatalities due to the respiratory illness, created an emergency response protocol that became law in 2006.

In California's case, Huff said he had never even heard of Mylan until the recent uproar over the EpiPen price increases. But the company is listed as a supporter of his bill, and FARE, partially funded by Mylan, was an official sponsor.

To address recent questions about its funding from Mylan, FARE announced Wednesday it would no longer accept money from epinephrine device makers until there's “meaningful competition.” FARE asserts that the money it received from Mylan has helped fund its education work, not its advocacy.

It didn't disclose exactly how much of its funding came from Mylan before Wednesday's announcement, but said contributions from corporate partners amounted to less than 10 percent of its budget.

“In some states, momentum has been garnered by a fatality,” said Jennifer Jobrack, senior national director of Advocacy at FARE, who said local lawmakers and activists call them in for help to craft policy.

“Legislators are looking for something they know will have a positive impact,” Jobrack said.

Virginia's law, passed in 2012, came after Amarria Johnson died at a Chesterfield County school from a reaction to peanuts. A Texas teenager's death from fire ant bites led to that state's law permitting epinephrine in schools.

President Barack Obama disclosed his daughter's peanut allergy when he signed off on the 2013 federal “EpiPen law,” which gives financial incentives to states that require the medication in schools. Co-author of the federal legislation, Rep. Steny Hoyer, D-Md., cited his 11 year-old granddaughter's peanut allergy when the EpiPen law passed the House. FARE and Mylan supported that effort as well.

With the help of these laws, Mylan's EpiPens are at 63,000 schools nationwide and the company has distributed 500,000 of them for free through EpiPens4Schools.

New York State's Attorney General announced Tuesday it will investigate Mylan to determine whether it introduced “anticompetitive terms” into school contracts. Stat recently reported that participants of Mylan's EpiPen4schools program had to agree not to purchase EpiPen-like products for twelve months in order to get a discount.

The school give-away program brings visibility and credibility to the EpiPen brand, building a consumer base beyond schools.

“It's kind of like the first hit's for free,” said Nicholson Price, an assistant professor at the University of Michigan Law School. “You want to start people off with your product, and getting these products in at schools is a great way.”

Mylan also has a virtual monopoly on epinephrine auto-injectors simply because there are almost no other products like it, either branded or generic.

Mylan has a patent on the drug-device combo until 2025. If companies want to make a generic EpiPen, they have to sue Mylan in court to try to invalidate its exclusive rights on the injector, according to Jacob Sherkow, an associate professor at New York Law School.

Trying to create an EpiPen generic is an expensive and risky endeavor, said Sherkow. Even if a company is successful in court, manufacturing the device, which must be identical, is also challenging.

Copying a chemical compound, like ibuprofen, is easier than reproducing a piece of hardware, like the iPhone, said Sherkow. Patents are publicly available, and can act as an “instruction manual,” but a lot can go wrong in the actual production of EpiPen syringes.

“The drug inside can't degrade or leak, they need to withstand shipping, they need to work at a wide range of temperatures, they need to be handled safely to not accidentally inject the user with the needle,” said Sherkow.

Teva Pharmaceuticals took on these challenges. It sued to invalidate Mylan's patent in court so that it could make a generic version of EpiPen, and successfully got the green light to do so through a settlement agreement. But Teva has yet to win FDA approval to release the product.

Other companies have tried to make their own version of the epinephrine injector without attempting to copy the EpiPen. But their efforts haven't been very successful either.

Amedra pharmaceuticals makes Adrenaclick, which has an injector with two caps (EpiPen only has one). But Amedra has limited manufacturing capabilities for the device and a barely visible market share, according to Price.

Auvi-Q, made by Sanofi, was taken off the market after concerns the device wasn't dispensing the proper dose of epinephrine.

More epinephrine products will be on the market in 2017. Teva's generic EpiPen is expected to be reintroduced then, and Mylan will put out its own generic in the coming weeks.

It's too early to tell if more consumer choices will bring down EpiPen's price.

This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.

Former Kaiser Health News intern Zhai Yun Tan contributed to this report.

Wednesday, 7 September 2016

Study Finds Benefits When Seniors Call Shots To Help Them

A federally funded project that researchers say has potential to promote aging in place began by asking low-income seniors with disabilities how their lives at home could be better, according to a study released Wednesday.

At the end of the program, 75 percent of participants were able to perform more daily activities than they could before and symptoms of depression also improved, the researchers said in the journal Health Affairs. Called Community Aging in Place, Advancing Better Living for Elders, or CAPABLE for short, the program was funded by the Center for Medicare & Medicaid Innovation.

The seniors who took part were each paired with a team for five months that included an occupational therapist, who made six visits; a registered nurse, who made four; and a handyman, who worked a full-day at the participant's home installing assistive devices and doing repairs, according to the study.

The nurses and therapists helped participants identify three achievable goals for each member of the team and identify what barriers had to be overcome. For example, the therapist might survey a house for safety issues such as unsafe flooring, poorly lit entrances and railings in disrepair. The therapist then worked with the elderly person to identify assistive devices, repairs or modifications that could help achieve the participant's goals. Next, the therapist created a work order for the handyman that prioritized those goals within a $1,300 budget for each dwelling.

Spending on assistive devices and home repairs ranged from $72 to $1,398 for each participant, the researchers said.

They studied 234 adults older than 65 who participated in CAPABLE, all eligible for both Medicare, the government health insurance plan for seniors, and Medicaid, the government health insurance plan for low-income people.

All participants had trouble with routine tasks in a group of eight known as activities of daily living. They include bathing, dressing, using the toilet and walking across a small room. On average, participants had trouble with 3.9 tasks at the start, but improved to just two by the end of the program.

Researchers said they could not conclude that the participants' improvements were due to the CAPABLE program because the project was funded without a control group to make scientific comparisons.

Sarah Szanton, the lead investigator and creator of CAPABLE, said the program hinges on two ideas. One is that environment influences health and the second is that seniors should set goals to improve their health. Seniors in her study were less depressed when they needed to rely less on others, she said.

Senior woman holding hands with doctor in home

Instead of dictating health goals to the patients, the therapist's first two visits were about listening to what the seniors thought their biggest problems were and creating plans on how to tackle them.

“There is strength to writing down those ideas, it shows [the patients] that they are active and resilient,” said Szanton, a nurse practitioner in West Baltimore and an associate professor of health policy and management at Johns Hopkins University in Baltimore.

For months after the program ended, she said, participants called to tell her they were still setting goals and working on accomplishing them. She saw that as her low-income patients aged, their environments became the biggest barriers to good health. She had patients who had to crawl to the front door to let her in because their homes weren't built to accommodate a wheelchair.

The long-term effects of CAPABLE are still being studied by the National Institutes of Health and the Center for Medicare and Medicaid Innovation.

Though the cost savings are unknown, Szanton said it isn't hard to see how CAPABLE could save money in the long run. The program cost around $3,000 per participant, but according to federal data, a semi-private room in a nursing home costs an average of $6,235 per month.

A version of CAPABLE is being studied in Michigan as a potential cost-saving program, and Szanton envisions it being incorporated into Medicare Advantage plans, accountable care organizations and Medicaid Waiver programs aimed at keeping people out of nursing homes.

KHN's coverage of aging and long-term care issues is supported by The SCAN Foundation.

Tuesday, 6 September 2016

EpiPen Controversy Fuels Concerns Over Generic Drug Approval Backlog

Consumers and Congress members pushing for cheaper alternatives to the EpiPen and other high-priced drugs are seeking answers about a stubborn backlog of generic drug applications at the Food and Drug Administration that still stretches almost four years.

As of July 1, the FDA had 4,036 generic drug applications awaiting approval, and the median time it takes for the FDA to approve a generic is now 47 months, according to the Generic Pharmaceutical Association, or GPhA. The FDA has approved more generics the past few years, but a flood of new applications has steadily added to the demand.

By comparison, the European Medicines Agency, Europe's version of the FDA, has just 24 generics or biologically-based “biosimilars” awaiting approval. (The FDA's count does not include biosimilars.) And the EMA along with the European Commission, which handles approval of marketing materials, are approving generics and brand name drugs in about a year on average, according to the EMA.

Critics say getting generic alternatives to the U.S. market for products like EpiPen is still taking far too long.

“We are concerned that Mylan (maker of the EpiPen) has not faced much competition for its product,” five U.S. senators wrote in August to FDA Commissioner Dr. Robert Califf, adding that one of EpiPen's non-generic competitors, Auvi-Q was recalled in October, granting Mylan a near monopoly. “News reports indicate that generic versions of the EpiPen have been subject to additional questioning by the FDA and have yet to be approved.”

Last week, three members of the House Committee on Energy and Commerce wrote a similar letter to the FDA, seeking information about the EpiPen generic applications it has received and how they've been prioritized.

When asked whether the FDA holds any responsibility for the lack of EpiPen competition, FDA spokesman Kristofer Baumgartner said he couldn't comment on pending applications or confirm their existence, citing confidentiality rules. But he stressed that the FDA pushes pending applications for drugs with no current generics to the front of the line and approved a record number of generics in 2015.

“The FDA is confident that the overall trend in actions on generic drug applications will be one of continuing improvement,” Baumgartner said.

In March, Teva Pharmaceuticals told investors that its generic version of EpiPen - the life-saving allergy treatment – was rejected by the FDA, and that it wouldn't be able to launch the generic until at least 2017. Adamis Pharmaceuticals reported a similar rejection from the FDA for its EpiPen generic in June.

Mylan has said it will offer a $300 generic in the coming weeks. Because Mylan also makes the brand name product, it will not have to wait in line behind other pending generics. And Dr. James Baker, the CEO and chief medical officer of the advocacy group Food Allergy and Research Education, said this may deter other generic manufacturers from seeking approval.

Adrenaclick is the only other epinephrine auto-injector on the market, but it is not a generic for EpiPen and cannot be swapped out at the pharmacy if a doctor has written a prescription for EpiPen. It's also not widely available, Baker said.

“You call up 100 pharmacies, and maybe 10 have the device, from what we gather,” Baker said of Adrenaclick, adding that several factors have allowed EpiPen's price tag to swell over the years. “Is Mylan doing anything illegal? No. It's taking advantage of all these things to take the market and basically push it to an extreme.”

Efforts To Speed The Approval Process

The FDA's generic backlog isn't a new problem. In 2012, it was so large that it prompted the government to start charging user fees to generic manufacturers to provide the funds for the FDA to speed the process. The fees built on the 20-year-old Prescription Drug User Fee Act, which required brand name drug manufacturers to pay fees to increase FDA efficiency. In the first three years, the FDA collected $1 billion from generic drug manufacturers.

The fees were used to hire an additional 1,000 employees, and put the Office of Generic Drugs on par with the Office of New Drugs by re-organizing it, and moving it to the FDA's main campus from four buildings in Rockville, Maryland. The funds were also used to replace the office's information technology system and implement a few other changes.

As the FDA notes on its website, “Additional resources will enable the Agency to reduce a current backlog of pending applications, cut the average time required to review generic drug applications for safety, and increase risk-based inspections.”

In October 2012, there was a backlog of 2,868 generic drugs awaiting approval, and the FDA said it would take a “first action” on 90 percent of these drugs by 2017. This summer, the agency met its goal a year early, but a first action isn't an approval. Only 1,551 generics have been approved since the fees were initiated, and that includes some extras that weren't considered part of the official backlog. So the agency has only approved about half of the backlogged generics that were awaiting approval in 2012.

“Most applications from the backlog will need to come back to FDA for additional review due to deficiencies in the submissions, before approval is possible,” the agency said in a statement in responses to questions.

The GPhA argues that the agency has declared applications to be “of 'poor quality' because they don't meet new, more recent standards updated while these applications sit in the backlog.”

The applications for generic drugs have continued to pile up even as the FDA approved a record number of generics in 2015 and again in the first seven months of 2016. The number of generic drug applications tripled from 2002 to 2012, according to January congressional testimony from Janet Woodcock, who directs the FDA's Center for Drug Evaluation and Research.

Still, some observers are hopeful.

“I think that it is an optimistic picture overall … at the FDA, there's been a lot of progress, and I think there is more to be made,” said Dr. Aaron Kesselheim, who leads a research program at Harvard Medical School and Brigham and Women's Hospital. “This is not something that people should think has been solved at this point. It's totally an ongoing process.”

KHN's coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

Thursday, 1 September 2016

What Happens When A Living Kidney Donor Needs A Transplant?

Becoming a living kidney donor can be a heroic act, but it has its downsides: increased risks of health complications and occasionally, diseases that may create the need for the donor to have a kidney transplant later in life.

In recognition of these possible consequences, living kidney donors who are in need of a transplant have, since 1996, been given priority status to shorten their time on the waiting list.

But according to a study published Thursday in the Clinical Journal of the American Society of Nephrology, prior living donors do not always receive that priority status in a timely manner. Some had to wait for years and go through dialysis before moving to the front of the line - while some possibly never got to priority status.

“This is a big deal to donors and the transplant community,” said Jennifer Wainright, an analyst at the United Network for Organ Sharing research department and the study's lead author. “Living kidney donors should know that they are entitled to priority … if they ever need a kidney, and also that most prior living donors receive their transplant quickly.”

Wainright stumbled upon this issue when she was examining data on donors, waitlist candidates and transplant recipients from the national Organ Procurement and Transplantation Network for another project.

“We put the original project on hold, explored the data, and figured out a way for UNOS to help transplant programs try to prevent the problem in the future,” she said.

The researchers sought to characterize how quickly prior living donors were added to and activated on the transplant list. They studied data related to living donors and their transplant needs from January 2010 through July 2015. During that period, 210 transplant candidates who were prior living donors with priority status were added to the transplant waiting list. As of Sept. 4, 2015, 167 of them received deceased donor transplants, six received living donor transplants, two died, five were too sick for transplants and 29 were still waiting.

Because of the “priority” designation, most of these patients were able to receive transplants quickly, the study found. But a number waited a long time.

For example, among the living donors studied, only 40.7 percent were added to the transplant waiting list before they needed dialysis, which is a treatment that becomes necessary when the kidneys are no longer functioning optimally. Half of the patients in the study were on dialysis for 332 days or longer before their priority was recognized.

The process of requesting the priority status goes like this: If a prior living donor needs a kidney transplant, the transplant program at the hospital will submit information and contact the UNOS Organ Center to request priority. The center is supposed to complete the request within a day. Patients healthy enough to receive the transplant immediately will be listed in an active status.

The reasons for the delays in this process detected by the study may be, in part, due to a patient's ill health or to paperwork and bureaucratic problems. These can include incomplete data submission and insurance issues, or a lack of awareness among patients and transplant programs about living donors' priority.

In an effort to smooth out the process and raise awareness among living donors and transplant programs, UNOS since last year has linked their list of living donors with the current kidney waiting list. The goal is to identify transplant candidates who were living donors but have yet to receive priority status. UNOS will then contact the person's transplant program to see that the situation is addressed.

But there are limitations to the data collection. The data tracking living donors only goes back to 1987, and have only included Social Security numbers since 1994. If a person donated a kidney before 1994 and changed his or her name, UNOS wouldn't be able to identify the person - thus still missing prior living donors who may have not been informed of their priority status.

Another solution Wainright identifies is ensuring use of the current OPTN policy that requires transplant programs to inform living donors about their priority on kidney waiting lists if they need a transplant after donation.

Between Sept. 2, 1996, and July 31, 2015, a total of 422 living donors were added to the kidney transplant waiting list. According to the National Kidney Foundation, being a living kidney donor is relatively common - there were 5,538 living kidney donors in 2014 compared with 7,761 deceased donors. Living donors may face a 25 to 35 percent permanent loss of kidney function after donation on average, but their risks of getting end stage renal disease less than 1 percent 15 years after the donation.

Peter Reese, assistant professor of medicine at the University of Pennsylvania School of Medicine, said his center always makes sure the living donors know about their right to a priority status. He was not associated with the study.

“If you tell kidney donors that, they will remember,” he said. “I'm surprised by this UNOS data, I think it's a shame that centers are not getting their donors registered in a timely way.”