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Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program is a program that grants a voucher for priority review to a drug developer as an incentive to develop treatments for disease indications with limited profitability.
Priority review vouchers are currently earned by pharmaceutical companies for the development and approval of drugs treating neglected tropical diseases, rare disease, and "medical countermeasures" for terrorism. The voucher can be used for future drugs that could have wider indications for use, but the company is required to pay a fee (approximately $2.8 million) to use the voucher.
When seeking approval for a drug, manufacturers can apply to the FDA for priority review. This is granted when a drug is intended to treat a serious condition and would "provide a significant improvement in safety or effectiveness" over currently available treatments. A priority review voucher can be used when a drug does not fit these requirements, but the company wishes to expedite the review process.
In 2007, Title XI of the Food and Drug Administration Amendments Act of 2007 created the priority review voucher program for neglected tropical diseases. This was extended in 2012 by the Food and Drug Administration Safety and Innovation Act to include rare pediatric diseases. The act built upon the tropical disease system and made amendments including a shorter notification to the FDA before exercising a voucher, a designation system so that early in the drug development cycle sponsors may use the possibility of earning a voucher in their valuation of their company, a requirement of a marketing plan and reporting of marketing, and indefinite transferability of the voucher. In 2016, medical countermeasures were added to the program.
A priority review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. The 2002 amendments to PDUFA set a goal that a standard review of a new drug application be accomplished within a ten-month time frame. The FDA goal for completing a priority review is six months. Priority review status can apply both to drugs that are used to treat serious diseases and to drugs for less serious illnesses.
The distinction between priority and standard review times is that additional FDA attention and resources will be directed to drugs that have the potential to provide significant advances in treatment. Such advances can be demonstrated by, for example: evidence of increased effectiveness in treatment, prevention, or diagnosis of disease; elimination or substantial reduction of a treatment-limiting drug reaction; documented enhancement of patient willingness or ability to take the drug according to the required schedule and dose; or evidence of safety and effectiveness in a new subpopulation, such as children.
A request for Priority Review must be made by the drug company. It does not affect the length of the clinical trial period. FDA determines within 45 days of the drug company's request whether a priority or standard review designation will be assigned. Designation of a drug as "priority" does not alter the scientific/medical standard for approval or the quality of evidence necessary. Safety requirements for a priority review are equal to that of a standard review.
The amendment can be found on page 150 of the Food and Drug Administration Amendments Act of 2007.
Under current Prescription Drug User Fee Act targets, the FDA aims to complete and act upon reviews of priority drugs within six months instead of the standard ten-month review period. Actual FDA review timelines, however, can be longer than the target PDUFA review periods, particularly for new products that haven't previously been approved for any indications. Economists at Duke University, who published on this concept in 2006, estimated that priority review can cut the FDA review process from an average of 18 months down to six months, shortening by as much as a full year the time it takes for the company's drug to reach the market.
An intangible benefit of the voucher is the value created for a company if the faster review provides them "first mover advantage," allowing the voucher holder's product to be introduced ahead of a similar, competing product. By taking advantage of existing market forces, patients in the developing world can have faster access to lifesaving products that may not otherwise be developed. And sponsors of neglected disease drugs can be rewarded for their innovations
Sponsors must inform the FDA of their intention to use a priority review voucher 90 days before submission. Before the Adding Ebola to the FDA Priority Review Voucher Program Act in 2014, this requirement was 365 days, which was a hindrance to the process of speedy review, as companies do not typically determine when drugs will be submitted until the results of safety studies are available.
Companies may also sell vouchers to other drug companies. Thus far, priority review vouchers have sold for $50–350 million.
| +Vouchers have been awarded for the following: !Program !Drug !Indication !Company !Year | ||||
| Tropical disease | Coartem | Malaria | Novartis | |
| Tropical disease | Sirturo | Multi-drug-resistant tuberculosis | Janssen Pharmaceutica | |
| Rare pediatric disease | Vimizim | Morquio syndrome | BioMarin Pharmaceutical | |
| Tropical disease | miltefosine | Leishmaniasis | Knight Therapeutics | |
| Rare pediatric | Unituxin | Neuroblastoma | United Therapeutics | |
| Rare pediatric | cholic acid | Zellweger syndrome | Asklepion Pharmaceuticals | |
| Rare pediatric | Xuriden | Orotic aciduria | Wellstat Therapeutics | |
| Rare pediatric | Strensiq | Hypophosphatasia | Alexion Pharmaceuticals | |
| Rare pediatric | Sebelipase alfa | Lysosomal acid lipase deficiency | Alexion | |
| Tropical disease | Vaxchora | Cholera prevention | PaxVax | |
| Rare pediatric | Exondys 51 | Duchenne muscular dystrophy | Sarepta Therapeutics | |
| Rare pediatric | Spinraza | Spinal muscular atrophy | Ionis Pharmaceuticals | |
| Rare pediatric | Emflaza | Duchenne muscular dystrophy | Marathon Pharmaceuticals | |
| Rare pediatric | Brineura | Batten disease | BioMarin Pharmaceutical | |
| Tropical disease | benznidazole | Chagas disease | ChemoResearch | |
| Rare pediatric | Kymriah | B-ALL | Novartis | |
| Rare pediatric | Mepsevii | Sly syndrome | Ultragenyx | |
| Rare pediatric | Luxturna | RPE65-mutated retinal dystrophy | Spark Therapeutics | |
| Rare pediatric | Crysvita | X-linked hypophosphatemia | Ultragenyx | 2020 |
| Tropical disease | Moxidectin | Onchocerciasis | Medicines Development for Global Health | |
| Rare pediatric | Epidiolex | Lennox-Gastaut syndrome | GW Pharmaceuticals | |
| Material threat countermeasure | Tpoxx | Smallpox | SIGA Technologies | |
| Tropical disease | Krintafel | Malaria | GlaxoSmithKline | |
| Rare pediatric | Revcovi | Adenosine deaminase-SCID | Leadiant Biosciences | |
| Rare pediatric | Gamifant | Haemophagocytic lymphohistiocytosis | Novimmune | |
| Tropical disease | Egaten | Fascioliasis | Novartis | |
| Rare pediatric | Symdeko | F508del cystic fibrosis | Vertex Pharmaceuticals | |
| Tropical disease | Dengvaxia | Dengue | Sanofi | |
| Rare pediatric | Zolgensma | Spinal muscular atrophy | AveXis | |
| Tropical disease | Pretomanid | Tuberculosis | TB Alliance | |
| Material threat countermeasure | Jynneos | Smallpox | Bavarian Nordic | |
| Rare pediatric | Trikafta | Cystic fibrosis | Vertex Pharmaceuticals | |
| Tropical disease | Ervebo | Ebola | Merck & Co. | |
| Capmatinib | MET exon 14 skipping mutated non-small cell lung cancer | Novartis | ||
| KTE-X19 | Mantle cell lymphoma | Kite Pharma | ||
| Selpercatinib | RET fusion-positive non-small cell lung cancer | Eli Lilly | ||
| elantamab mafodotin | Multiple myeloma | GlaxoSmithKline | ||
| Cedazuridine and decitabine | Chronic myelomonocytic leukemia | Astex Pharmaceuticals | ||
| Rare pediatric | Vyondys 53 | Duchenne muscular dystrophy | Sarepta Therapeutics | 2020 |
| Rare pediatric | Oxlumo | Primary hyperoxaluria type 1 | Alnylam Pharmaceuticals | 2020 |
| Rare pediatric | Rethymic | Congenital athymia | Enzyvant Therapeutics | 2021 |
The pediatric voucher program includes changes to the voucher program. First, the pediatric treatment developer can ask the FDA in advance for an indication of whether the disease qualifies as a rare, pediatric disease.
The awardee must market the drug within 365 days of approval, or the voucher may be revoked. Within five years of approval, the manufacturer must submit a report containing information on the estimated population in the United States suffering from the rare pediatric disease, the estimated demand in the United States for such rare pediatric disease product, and the actual amount of such rare pediatric disease product distributed in the United States.
The Advancing Hope Act of 2016 reauthorized the program until December 31, 2016 and instructed the GAO to compile a report on the effectiveness of the program.
On a technical level, S. 2917 added "Filoviruses" to the priority review list. The Ebola virus is a type of Filovirus. According to the Congressional Budget Office, enactment of the law does not have an effect on the federal budget.
In 2014, Regeneron Pharmaceuticals and Sanofi purchased a PRV that BioMarin had won for a recent rare disease drug approval for $67.5 million; the voucher cut four months off the regulatory review time for alirocumab and was part of their strategy to beat Amgen to market with the first approval of a PCSK9 inhibitor. In 2015, Retrophin sold a PRV to Sanofi for around $245 million, and later the same year, United Therapeutics Corp. sold a PRV for a drug for a rare pediatric disease to AbbVie Inc. for $350 million.Chelsey Dulaney, United Therapeutics Sells Priority-Review Voucher to AbbVie for $350 Million, Wall Street Journal (August 19, 2015). In 2016–2018, the value of a voucher ranged from $125 million to $200 million, down from its peak in 2015.Conor Hale, Jazz grabs Spark's priority review voucher for $110M, Fierce Biotech (April 30, 2018).
Pediatric rare diseases are any disease that primarily affects people under the age of 18 and affects 200,000 or fewer people in the United States. Medical countermeasures are drugs to be used "in the event of a public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, a naturally occurring emerging disease, or a natural disaster."
The priority review voucher may tax FDA resources. To mitigate this, use of the priority review voucher includes an extra fee paid by manufacturers to the FDA and requires that voucher bearers provide FDA with 90 days' notice before using a voucher.
Critics of the FDA allege that priority review might not be safe. Priority review should not, however, be confused with accelerated approval or fast track designation. Priority review does not omit safety or efficacy studies or require approval within a given time frame. It sets a target of 6 rather than 10 months for FDA review. Nevertheless, a study in 2008 claimed that new molecular entities approved in the two months before the first review deadlines showed a higher rate of postmarketing safety problems than drugs approved at other times. Nardinelli and colleagues (2008) of the FDA, however, wrote that they were not able to replicate the findings and that the findings might be driven by HIV-AIDS therapies. Following the Nardinelli piece, Carpenter acknowledged several errors in their data set and demonstrated errors in the FDA's and Nardinelli's data; Carpenter and colleagues report that the original associations between last-minute approvals and safety problems hold.
There have also been complaints that the priority review voucher encourages innovation, but does not pay for access to existing therapies. Funding from governments or foundations might be needed to purchase treatments for poor people. Aidan Hollis of the University of Calgary has commented that the proposal does not address "the access problem, but helps to increase incentives through creating distortions in markets in developed countries". This is entirely a separate issue from the promotion of research intended by the priority review program.
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According to Bill Gates,
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