The US Congress created the priority review voucher program in 2007 based on a 2006 Health Affairs paper (Ridley et al. 2006). Under the law, following approval by the Food and Drug Administration (FDA) of a treatment for a neglected or rare pediatric disease, the developer receives a voucher for priority review for a different drug. Two drugs receive priority review for each voucher: the drug winning a voucher for a neglected or rare pediatric disease, and the drug using a voucher for another indication.
The voucher may be sold. For example, a small company might win a voucher for developing a drug for a neglected disease, and sell the voucher to a large company for use on a commercial disease.
Priority review means that the FDA aims to render a decision in 6 months. In contrast, the FDA aims to complete a standard review in about 10 months.
The voucher program is intended to reduce two types of inefficiency. First, the voucher program motivates more treatments for neglected and rare diseases. Second, the voucher program speeds approval of potential blockbuster therapies in the US, getting US patients access to these treatments more quickly.
By moving a drug to faster review, there is the potential to slow other drugs. To provide FDA with more resources and mitigate this cost, the voucher holder must pay the FDA an additional user fee ($2,457,140 in fiscal year 2019). The FDA can include in its budget request the expectation of redeemed vouchers. For example, if the FDA consistently has 4 vouchers redeemed each year, it can consistently request an extra $10 million.
The voucher has three effects on commercial value: the competitive effect, the time-value of money effect, and the exclusivity effect (Ridley and Régnier 2016).
Because of the voucher program, investors are more willing to provide funding to entrepreneurs working on drugs for neglected diseases. For example, NanoViricides was developing drugs for viruses that have large sales potential in markets such as the United States, such as HIV-AIDS and flu. They are now developing a drug for dengue because of the voucher incentive. According to Dr. Eugene Seymour, CEO of NanoViricides,
"After learning of the priority review voucher (PRV) program, I pushed my company to initiate development of a drug for dengue/dengue hemorrhagic fever, then the only viral disease on the FDA eligibility list for a PRV. The drug, built on our NanoViricides platform, has since undergone initial testing... I've had serious discussions with many different entities, including the head of the dengue branch of the US Centers for Disease Control who has pledged clinical trial support as well as a large Foundation in South America who would like to pursue discussions regarding distribution of the drug after it's approved in the US. None of this would have happened had there not been a PRV program in place" (Email correspondence with Dr. Seymour, November 2015).
Likewise, the Global Health Investment Fund announced that it provided $10 million to non-profit drug developer Medicines Development of Australia to complete registration of moxidectin, a drug for river blindness. Because river blindness does not affect people in rich countries, moxidectin had been languishing on the shelf of a drug manufacturer. If it is approved, then it can help speed the eradication of river blindness. Furthermore, if the drug is approved and wins a priority review voucher from the Food and Drug Administration, the Fund will share in some of the rewards from sale of the voucher. The fund can then use some of the returns to re-invest in global health. According to Mark Sullivan, the CEO:
"Medicines Development for Global Health's ability to attract the finances required to complete the final stages of moxidectin's development was a direct result of the value of the voucher. Even then, the risk/benefit debate diminished only once two commercial voucher transactions had taken place and the theoretical market value had become a confirmed value. Without this mechanism, moxidectin would have been a missed opportunity for global health" (Email correspondence with Mr. Sullivan, January 2016).
Furthermore, PATH announced in a press release:
"PATH is pleased to announce that, together with a consortium of government, nonprofit, and commercial partners, it intends to seek US Food and Drug Administration (FDA) approval for tribendimidine (TrBD) as a significantly improved treatment for hookworm infections... This groundbreaking collaboration among diverse stakeholders has been made possible by the FDA's tropical disease priority review voucher (PRV) program" (Press release, January 2017).
To be eligible for a voucher, the drug or vaccine must satisfy the following criteria.
See "Extension to Rare Pediatric" below for eligibility for a pediatric vouchers.
|2||2012||Tuberculosis||Sirturo (bedaquiline)||Janssen (JNJ)|
|3||2014||Morquio A syndrome||Vimizim (elosulfase alfa)||BioMarin|
|5||2015||High-risk neuroblastoma||Unituxin (dinutuximab)||United Therapeutics|
|6||2015||Rare bile acid synthesis disorders||Cholbam (cholic acid)||Asklepion|
|7||2015||Hereditary orotic aciduria||Xuriden (uridine triacetate)||Wellstat|
|8||2015||Hypophosphatasia||Strensiq (asfotase alfa)||Alexion|
|9||2015||Lysosomal acid lipase (LAL) deficiency||Kanuma (sebelipase alfa)||Alexion|
|11||2016||Duchenne muscular dystrophy||Exondys 51 (eteplirsen)||Sarepta|
|12||2016||Spinal muscular atrophy (SMA)||Spinraza (nusinersen)||Biogen|
|13||2017||Duchenne muscular dystrophy||Emflaza (deflazacort)||Marathon|
|14||2017||Batten disease||Brineura (cerliponase alfa)||BioMarin|
|16||2017||B-cell acute lymphoblastic leukemia||Tisagenlecleucel||Novartis|
|17||2017||Mucopolysaccharidosis (MPS) VII||Mepsevii||Ultragenyx|
|18||2017||Biallelic RPE65 mutation-associated retinal dystrophy||Luxturna (voretigene neparvovec-rzyl)||Spark|
|19||2018||X-linked hypophosphatemia (XLH)||Crysvita (burosumab-twza)||Ultragenyx|
|20||2018||Onchocerciasis (river blindness)||Moxidectin||Medicines Development|
|21||2018||Lennox-Gastaut or Dravet syndromes||Epidiolex (cannabidiol)||GW Research|
|22||2018||Small pox||TPOXX (tecovirimat)||Siga|
|24||2018||Adenosine Deaminase-Severe Combined Immunodeficiency (ADA-SCID)||Revcovi (elapegademase-lvlr)||Leadiant|
|25||2018||Primary haemophagocytic lymphohistiocytosis||Gamifant (emapalumab-lzsg)||Sobi (Novimmune)|
|27||2019||Cystic fibrosis||Symdeko (tezacaftor/ivacaftor)||Vertex|
|29||2019||Spinal muscular atrophy||Zolgensma||Novartis (AveXis)|
The price of the voucher depends on supply and demand. The voucher's value derives from three factors: shifting sales earlier, longer effective patent life due to earlier entry, and competitive benefits from earlier entry relative to competitors. Top-selling treatments can yield billions in sales each year, so being approved months earlier can be worth hundreds of millions of dollars to the voucher holder (Ridley et al. 2006; Ridley and Régnier 2016). The value of the voucher will depend on the drug's therapeutic class (Noor 2009).
In 2014, Sanofi/Regeneron purchased the first voucher sold for $67.5 million. In 2015, Sanofi was back in the market with a $245 million voucher purchase. The figure below illustrates voucher prices over time.
In 2015, European regulators approved Amgen's cholesterol drug Repatha 2 months ahead of Sanofi/Regeneron's Praluent. But in the US, the order was reversed with Praluent a month ahead of Repatha, because Sanofi/Regeneron used a priority review voucher. Read more at Fierce Pharma.
Priority review vouchers do not expire. Furthermore, the priority review voucher program for neglected diseases (enacted in 2007) does not sunset. However, the program for rare, pediatric diseases will expire in October 2020, although a drug designated as a rare pediatric treatment can still receive a voucher if the drug is approved by October 2022. Furthermore, the program can be renewed, and Congress has renewed the program several times already.
David Ridley, Henry Grabowski, and Jeff Moe proposed the voucher in a paper published in 2006. David presented the team's draft paper at several conferences, including the June 2004 meeting of the Drug Information Association, the January 2005 meeting of the American Economic Association, and the July 2005 meeting of the International Health Economics Association. In 2006, the voucher proposal was the lead article in Health Affairs. After Health Affairs published the paper, David presented the paper at the National Press Club on March 7, 2006. After the press conference, Laura Blinkhorn (a reporter for Congressional Quarterly) told David that Senator Brownback (R-KS) would be interested. David and Jeff met with Senator Brownback and his staff (including Melanie Benning). Senator Brown (D-OH) and others joined Senator Brownback in sponsoring the bill. In a later issue of Health Affairs, Senator Brownback wrote, "After reading their proposal in Health Affairs, I met with Ridley and colleagues to discuss the idea further, and I subsequently drafted an amendment... Indeed, their idea is the heart of my Elimination of Neglected Diseases (END) amendment" (Brownback 2007).
In 2008, Bill Gates speaking at the World Economic Forum in Davos in 2008, said "But some of the highest-leverage work that government can do is to set policy and disburse funds in ways that create market incentives for business activity that improves the lives of the poor. Under a law signed by President Bush last year, any drug company that develops a new treatment for a neglected disease like malaria or TB can get priority review from the Food and Drug Administration for another product they've made. If you develop a new drug for malaria, your profitable cholesterol-lowering drug could go on the market a year earlier. This priority review could be worth hundreds of millions of dollars" (transcript, video, video excerpt).
Extension to Europe
Writing in The Lancet, David Ridley and Alfonso Calles Sanchez proposed extending the voucher to the European Union (Ridley and Calles Sanchez 2010). The proposed EU voucher would provide priority regulatory review through the European Medicines Agency, as well as accelerated pricing and reimbursement decisions by EU member states.
Extension to Patents
Inspired by the priority review voucher, in 2012 the United States Patent and Trademark Office (USPTO) launched a pilot program called Patents for Humanity" to encourage businesses to apply their patented technology to addressing humanitarian challenges. Winners receive a voucher with which they may (1) move a patent re-examination proceeding to the front of the queue; (2) move a patent appeal case in front of the Board of Patent Appeals and Interferences to the front of the queue; or (3) accelerate the examination of a patent with the goal of a final decision on the application within twelve months. Application categories include medical technology, food & nutrition, clean technology, and information technology. In 2013, the USPTO awarded ten acceleration certificates.
Extension to Rare Pediatric Diseases
In 2012, the U.S. President signed into law the FDA Safety and Innovation Act which included Section 908 the "Rare Pediatric Disease Priority Review Voucher Incentive Program". The act extended the voucher program to rare pediatric diseases on a trial basis.
To be eligible for a pediatric voucher, the drug or biological product must
|Legislative authority||FDAAA (2007) (PDUFA IV)||FDASIA (2012) (PDUFA V)|
|Voucher winner||Program expiration||None||October 2020 (2022 approval deadline for drugs with rare pediatric designations in 2020 or earlier)|
|Eligibility||List of neglected diseases (may be extended by Congress or Secretary of HHS)||Rare, pediatric diseases (may ask FDA in advance for an indication of whether disease qualifies as a rare, pediatric disease)|
|Obligations for voucher winner||None (other than public pressure)||Winner must market drug within a year and report to FDA about use of drug within five years|
|Voucher user||Notification||90 days prior to voucher redemption|
|Additional user fee||$2,457,140 in fiscal year 2019|
|Voucher expiration date||None|
Extension to Medical Countermeasures
In 2016, Congress extended voucher eligibility to medical countermeasures.
Program limitations pertaining to winners of vouchers (drugs for neglected and rare diseases):
Program limitations pertaining to users of vouchers (drugs which would have had standard review now receiving priority review):
This web page is maintained by David Ridley, one of the authors of the priority review voucher program.