THE CREATING HOPE ACT: THE RARE PEDIATRIC DISEASE PRIORITY REVIEW VOUCHER (PRV) INCENTIVE PROGRAM 21 U.S.C. 360ff
1. What is the Creating Hope Act?
2. What is a priority review voucher?
3. What is the purpose of priority review vouchers?
4. Why do we need an incentive to develop treatments for rare pediatric diseases?
5. How is a priority review an incentive and who pays for it?
6. How does the voucher process work?
7. Are the priority review vouchers effective?
8. What new drugs earned a voucher? How many vouchers have been sold and at what price?
9. How can I support Creating Hope Permanent Reauthorization Act of 2019?
Resources:
Legislative history of the PRV program
FDA Draft Guidance for Industry
GAO reports on priority review vouchers
Where can I learn more about vouchers?
What is the Creating Hope Act?
The Creating Hope Act, championed by Kids v Cancer and passed into federal law in 2012, created the pediatric rare disease priority review voucher program. The first voucher was awarded in 2014. The Creating Hope Act was reauthorized in 21st Century Cures Act in December 2016. The reauthorization is not permanent, and the Creating Hope Act sunsets (expires) in September 2020. We are working hard on a permanent reauthorization of the Creating Hope Act.
What is a voucher?
Priority review voucher (PRV) is an incentive program established by Congress and administered by the Food and Drug Administration to encourage development of treatments for rare pediatric diseases. Priority review voucher is awarded to a drug company if the company develops a drug for a rare pediatric disease and the drug is approved. The voucher allows the company to expedite the FDA review of a future drug. The company may sell the voucher to other companies that want to expedite drug reviews.
What is the purpose of priority review vouchers?
Priority review vouchers are an incentive for drug companies to develop drugs for rare pediatric diseases. The disease is rare if it affects fewer than 200,000 Americans. All childhood cancers are rare. There are about 6,400 rare diseases, 50% of them affect children. The goal of vouchers is to create new treatments developed specifically for kids and to increase the number of new treatments for rare diseases in kids.
Why do we need an incentive to develop treatments for rare pediatric diseases?
Drug development is a long, costly, and financially risky process. A company must secure funding from investors, pay researchers and scientists, and conduct pre-clinical and clinical trials. All of these activities must be funded before a company knows if a drug will be approved. Creating drugs for rare diseases takes the same effort as for other diseases but is often less profitable. When a disease has a large patient population, the company’s earnings might be higher than if there is a small number of patients for whom the drug is developed. Conducting clinical trials for rare diseases is more complicated as it is harder to enroll patients. Without an incentive, drugs companies are historically less likely to develop drugs for neglected tropical diseases and rare pediatric diseases.
How is a priority review an incentive and who pays for it?
A drug company spends on average 7-10 years creating a new medicine, and then submits an application to the Food and Drug Administration for approval. The usual FDA review takes about 10 months. A priority review is usually 6 months. The extra time is valuable to a drug company, as the new drug will reach the patients sooner and may beat a competitor’s drug to the market. The extra time the company gains does not cost taxpayers or patients anything. The FDA collects a priority review fee from the drug company. The FY 2020 fee is $2,167,116.
How does the voucher process work?
There are 3 steps:
1. A company must develop a treatment for a rare pediatric disease. Usually the company requests a rare pediatric disease designation prior to submitting a new drug application and requesting a voucher.
2. The FDA must approve the treatment and the voucher request. Upon approval, the FDA issues a voucher to the company.
3. The company presents the voucher to FDA when it wants to request a priority review of another drug, which can be for any disease that affect any population, such as diabetes or Alzheimer’s disease. Or:
The company may sell the voucher. The vouchers have been selling for $67 million-$350 million.
Are the priority review vouchers effective?
Yes. In the 20 years before the enactment of the Creating Hope Act, FDA approved only two drugs that had been developed specifically to treat a pediatric cancer: Erwinase and Clofarabine. Since 2014, when the first voucher has been issued, 22 new drugs for rare diseases in kids have been approved, including two drugs for childhood cancers.
Many vouchers have been sold, creating almost $2 billion in sales – a powerful incentive for the companies. Executives of pharmaceutical companies have expressed their interest in earning a voucher and have said it is a valuable incentive. And it has not cost patients or taxpayers a penny.
Drug companies are developing more drugs for rare pediatric diseases than before. During drug development process and prior to submitting a new drug application and requesting a voucher, companies apply to FDA for the rare pediatric disease designation (and/or other designations, such as orphan drug, breakthrough therapy, fast track, etc). The number of applications to FDA for rare pediatric disease designation – a signal from drug companies developing drugs for kids that they are interested in earning a voucher — has been rising steadily. (Not every drug that receives a rare pediatric disease designation will be approved, and the designation is not a guarantee of the voucher award.)
Rare Pediatric Disease Designation Requests Submitted and Priority Review Vouchers Issued, 2013-2019
*Rare pediatric disease designation was created by the Creating Hope Act in 2012.
What new drugs earned a voucher? How many vouchers have been sold and at what price?
The first rare pediatric disease (RPD) priority review voucher was awarded in 2014, two years after the Creating Hope Act was passed into law. Since then, a total of 22 RPD vouchers have been awarded. The vouchers have been sold for up to $350 million, and recently have been selling for about $100 million. See the list of issued and sold vouchers here.
How can I support Creating Hope Permanent Reauthorization Act of 2019?
The Creating Hope Act voucher program for drugs developed to treat children with life threatening illnesses is not permanent.
The Creating Hope Act passed in 2012, was reauthorized several times, and sunsets September 30, 2020. Under the sunset provisions, after September 30, 2020, FDA may only award a voucher if the drug has rare pediatric disease designation granted by that date. After September 30, 2022, FDA may not award any rare pediatric disease priority review vouchers.
At the same time, the tropical disease priority review voucher program is permanent. Twelve tropical disease vouchers have been awarded since 2009, compared with 22 pediatric disease vouchers awarded since 2014.
On September 20, 2019, a bill seeking permanent reauthorization of the Creating Hope Act, H.R.4439, was introduced in the House of Representatives by Rep. G.K.Butterfield (D-NC). It currently has 20 cosponsors. Permanent reauthorization is needed because the incentive is bringing new rare disease drugs to market — it works. Read more here.
Legislative history of the PRV program
The Creating Hope Act voucher is based upon a neglected tropical disease priority review voucher program that was signed into law as a provision of the Food and Drug Administration Amendments Act of 2007.
The Creating Hope Act was passed into law in 2012 as part of Food and Drug Administration Safety and Innovation Act, Public Law 112–144, Title IX, Sec. 908, Rare Pediatric Disease Priority Review Voucher Incentive Program. The vouchers awarded for development of drugs for rare pediatric diseases constituted 61% of all FDA-issued vouchers since then.
By enacting the Creating Hope Act pediatric PRV program – the Rare Pediatric Disease Priority Review Voucher Program, 21 U.S.C. 360ff Sec. 529— Congress created a market incentive for the development of drugs for rare pediatric diseases.
On December 13, 2016, President Obama signed into law the 21st Century Cures Act, reauthorizing the Creating Hope Act until September 2020. The U.S. Senate passed the 21st Century Cures Act and with it, reauthorization of the Creating Hope Act pediatric priority review voucher program, voting 94-5. Thank you to our sponsors, Congressmen G.K. Butterfield, Michael McCaul and Chris Van Hollen, and Senators Bob Casey and Johnny Isakson, for their commitment to children with cancer and other rare diseases. Thank you to the FDA for executing this critical program.
Pursuant to the 21st Century Cures, the Creating Hope Act pediatric PRV is reauthorized until September 20, 2020. Moreover, drugs that receive rare pediatric designations by that date will qualify for vouchers as long as they are approved by September 20, 2022.
On September 20, 2019, a bill seeking permanent reauthorization of the Creating Hope Act, H.R.4439, was introduced in the House of Representatives by Rep. G.K.Butterfield (D-NC).
We are working on making the Creating Hope Act permanent.
FDA Draft Guidance for Industry
In July 2019 FDA updated its guidance on the Creating Hope Act Priority Review Vouchers, entitled: Rare Pediatric Disease Priority Review Vouchers, Guidance for Industry, which the agency initially issued in November 2014.
For companies developing pediatric rare disease drugs:
The criteria for a Rare Pediatric Disease Product Application leading to a pediatric voucher are that a drug or biological product:
- Is for the prevention or treatment of a Rare Pediatric Disease;
- Contains no active ingredient that has been previously approved in any other application;
- Is submitted under section 505(b)(1) of this Act or section 351(a) of the Public Health Service Act;
- Itself qualifies for priority review;
- Relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for a pediatric population.
The term “rare pediatric disease” means a disease that is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years.
The Creating Hope Act provides for a rare pediatric designation process to create greater certainty earlier in the drug development process that a drug or biologic would qualify for a voucher, should it be approved. The request for a rare pediatric designation can be made at the same time or after a request for an orphan designation is made.
For companies wishing to exercise a voucher:
A sponsor who wishes to exercise a priority review voucher would likely have a large-market adult drug or biologic that would otherwise be reviewed by the FDA pursuant to a standard review. By exercising a priority review voucher, the sponsor would then be able to receive a priority review for that drug or biologic. This would get the drug or biologic to market more quickly, perhaps ahead of a similar competing drug or biologic, thereby generating significant value.
The priority review voucher program does not alter the criteria for a FDA approval. Drugs subject to priority review must still conform to all the FDA requirements to be approved.
A sponsor of a drug or biologic application that is the subject of a priority review voucher shall pay a user fee. The amount of the user fee shall be based on the difference between the average cost incurred by the FDA of a priority review and the average cost incurred by the FDA of a standard review. This amount shall be adjusted annually to reflect current costs. For fiscal year 2021, which starts October 1, 2020, the fee for exercising a priority review voucher was reduced to $1,360,879 from FY2020 fee of $2,167,116, and significantly less than the $2,457,140 fee in FY2019.
The Creating Hope Act provides that the sponsor must notify FDA of its intent to submit a drug application with a priority review voucher at least 90 days prior to submission. The user fee shall be due upon the notification.
Pursuant to the Creating Hope Act, the FDA may revoke a priority review voucher awarded if the Rare Pediatric Disease Product Application for which such voucher was awarded is not marketed in the United States within a year.
GAO reports
The Government Accountability Office has produced two reports on priority vouchers, including rare pediatric disease PRVs. The first report, published in March 2016, was titled “Too Early to Gauge Effectiveness of FDA’s Pediatric Voucher Program.” It stated: “Given that the typical drug development process often exceeds a decade, insufficient time has elapsed to determine whether the 3 year-old program has been effective.
The second report, titled “Drugs Development: FDA’s Priority Review Voucher Programs”, was published in January 2020. It states: “All 7 drug developers we spoke to indicated that the vouchers were a factor in their decisions.” Drug companies “indicated support for their reauthorizations, with some noting that PRV program expirations may negatively affect overall drug development and the willingness of drug sponsors to work in these areas.”
Where can I learn more about vouchers?
Please visit our Creating Hope Act news page.