Understanding The FDA Priority Review Voucher Program

An overview of the priority review voucher program for pharmaceutical regulatory and competitive intelligence professionals

Recently, the Food and Drug Administration (FDA) priority review voucher program (PRV) made headlines when the Wall Street Journal ran a piece describing a “lucrative secondary market” that has emerged as drug companies pay hundreds of millions of dollars to purchase vouchers.

With blockbuster treatments, high sales figures, fierce competition and legislative action in play, regulatory and competitive intelligence professionals need to know about priority review vouchers and how they change the game of drug review. What follows is a primer on the history of the program, key legislation, sales figures and major players to keep corporate intelligence professionals up to date on this small but important corner of the pharmaceutical regulatory affairs realm.

Priority review vouchers are an incentive, a sort of golden ticket, designed to encourage (and reward) companies who develop treatments for underfunded, neglected or rare diseases. A company bringing to market a new drug to treat, say, drug-resistant malaria in hard-hit tropical areas will receive a voucher guaranteeing expedited review of another drug at some later date. Priority review shortens the FDA’s decision deadline to six months (versus the standard ten months), which—if the drug in question is approved—can mean the drug reaches the market and begins generating profits much faster. (Vouchers do not guarantee drug approval, but they do shorten the time drug companies must wait for a decision from the FDA.)

The idea of “linking incentives for essential drugs in developing countries with ‘blockbuster’ drugs in the developed world” originally came from a 2006 paper in Health Affairs written by Duke University researchers. The paper inspired Senator Sam Brownback to draft legislation introducing the “priority review voucher” system, and the first vouchers were signed into law as part of the 2007 Food and Drug Administration Amendments Act (FDAAA) (see Sec. 1102, “Priority Review to Encourage Treatments for Tropical Diseases”).

Expansion of the Priority Review Voucher Program

While the original vouchers focused on incentivizing drugs for neglected tropical diseases, the program later expanded to include rare pediatric diseases. The 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) included the Rare Pediatric Disease Priority Review Voucher Incentive Program (see Sec. 529, “Priority Review to Encourage Treatments for Rare Pediatric Diseases”). (The Rare Pediatric Disease Priority Review Voucher Program is currently administered as part of the FDA’s Office of Orphan Products Development.)

In 2014, the Adding Ebola to the FDA Priority Review Voucher Program Act was signed into law, expanding the tropical disease voucher program and also making some notable changes to the program.

Summary of the Key Voucher Legislation At-a-Glance

For further information, the Regulatory Affairs Professionals Society provides an excellent Regulatory Explainer on priority review vouchers. Additional information for industry can be found in the 2014 FDA draft guidance entitled Rare Pediatric Disease Priority Review Vouchers, Guidance for Industry.

Limitations of Priority Review Voucher System

There are important limitations on pediatric priority review vouchers. As the law currently stands, the program will end on March 17, 2016 unless legislative action is taken. The FDASIA provision was written to trigger a one-year “sunset period” after the third pediatric voucher was issued; FDA’s approval of Cholbam on March 17, 2015 put the sunset clause into effect and also triggered a required review by the Government Accountability Office (GAO). The race is now on, as the existing vouchers become an even more valuable commodity and legislators, rare disease advocates and drug companies anxiously wait to see if the program will be renewed before the deadline.

The 21^st Century Cures Act, passed in 2015, includes a proposal for renewal of the Pediatric Priority Review Vouchers program which is described in detail by the FDA Law Blog. The Advancing Hope Act of 2015, introduced to the House in March of this year, would reauthorize and expand the PRV program for pediatric diseases; a similar Senate bill was introduced in July.

For now, though, uncertainty about the program’s future only fuels competition.

Where Priority Review Vouchers Are Used

Existing vouchers are seen as rare and precious commodities, and they command huge sales prices. Nine vouchers have been issued so far:

1. Novartis received a tropical disease voucher in 2009 for the malaria drug Coartem. Novartis later used the voucher, unsuccessfully, to fast-track the review of its arthritis drug Ilaris.
2. Janssen’s multi-drug resistant tuberculosis treatment Sirturo received priority review designation via the tropical disease program in 2012.
3. The first pediatric rare disease PRV was issued to BioMarin in 2014 for its congenital enzyme disorder treatment Vimizim. BioMarin sold its voucher to Regeneron in 2014 for $67.5 million. Regeneron and Sanofi later used the voucher to speed the review of their cholesterol drug Alirocumab, which was successfully approved.
4. Knight Therapeutics received a 2014 tropical disease voucher for the leishmaniasis drug Impavido. Knight sold the voucher to Gilead for $125 million. Gilead has used the voucher to speed a New Drug Application for an investigational HIV drug.
5. United Therapeutics was awarded a rare pediatric disease PRV in 2015 for Unituxin, which treats high-risk neuroblastoma. AbbVie later purchased the voucher for $350 million, and thus far has not announced plans for its use.
6. Asklepion Pharmaceuticals received the third, sunset-triggering pediatric PRV in March 2015 for its rare bile acid synthesis disorder treatment Cholbam. The PRV was transferred to Retrophin under terms of an existing agreement and later sold to Sanofi for $245 million. Some analysts have speculated that the voucher may be used (subscription or purchase required) to fast-track review of the diabetes treatment Lixilan.
7. Wellstat was issued a rare pediatric disease PRV in September 2015 for Xuriden, a drug to treat the rare metabolic disorder hereditary orotic aciduria. The company announced that it had entered into an agreement with AstraZeneca under which the voucher would be transferred to AstraZeneca upon approval.
8. Alexion Pharmaceuticals received a voucher under the pediatric rare disease program with the October 2015 FDA approval of Strensiq, a treatment for perinatal-, infantile- and juvenile-onset hypophosphatasia. Alexion CEO David Hallal later shared plans for the company to use the voucher for one of its own future products.
9. Alexion was awarded a second pediatric PRV in December 2015, this time for its lysosomal acid lipase deficiency (LAL-D) treatment Kanuma. The drug was approved for use in pediatric and adult patients.

The fate of the pediatric PRV program, as well as that of the unused existing vouchers, remains unclear. What is certain, however, is that demand for vouchers remains high, and both pharmaceutical regulatory affairs and competitive intelligence professionals should understand these PRV laws.