Priority Review Voucher Program Research Articles

Impact of Priority Review Voucher Eligibility on Research and Development of Medical Countermeasures.

The priority review voucher was established to incentivize research and development of treatments for traditionally underfunded diseases and was extended to medical countermeasures from 2016 to 2023, despite limited evidence of an association between the voucher program and increased product development. To determine whether the voucher program has incentivized initiation of new medical countermeasures in clinical trials, we created three cohorts of material threats: (i) COVID-19, (ii) opioid pharmaceutical-based agents, and (iii) all others. Using the Citeline Trialtrove database, we determined the number of medical countermeasures initiated in clinical trials from 2009-2016 and 2017-2023. Eligibility of COVID-19 products for the voucher was confirmed with the issuance of a voucher for remdesivir in October 2020, so we compared January 2020-October 2020 to November 2020-July 2023. We fit two Poisson models-before and after voucher creation-within each cohort. Among COVID-19 medical countermeasures, there was a decrease in the proportion of drugs initiated before (4.5%; 95% CI, 1.0 to 8.3%) vs. after voucher eligibility (-5.1%; 95% CI, -6.1 to -4.0%) (P = 0.01). Among opioid pharmaceutical-based agents medical countermeasures, the rate of new drugs initiated did not change from 2009-2016 (8.1%, 95% CI, -4.4 to 22.6%) to 2017-2023 (5.6%; 95% CI, -3.2 to 15.2%) (P = 0.82). Among all other medical countermeasures, the rate of new drugs initiated also did not change from 2009-2016 (6.6%; 95% CI, -5.6 to 20.8%) to 2017-2023 (-14.8%; 95% CI, -29.2 to 2.0%) (P = 0.15). The priority review voucher program was not associated with stimulating new clinical testing of investigational medical countermeasures.

Analysis of the first ten years of FDA’s rare pediatric disease priority review voucher program: designations, diseases, and drug development

BackgroundThe Rare Pediatric Disease (RPD) Priority Review Voucher (PRV) Program was enacted in 2012 to support the development of new products for children. Prior to requesting a voucher, applicants can request RPD designation, which confirms their product treats or prevents a rare disease in which the serious manifestations primarily affect children. This study describes the trends and characteristics of these designations. Details of RPD designations are not publicly disclosable; this research represents the first analysis of the RPD designation component of the program.ResultsWe used an internal US Food and Drug Administration database to analyze all RPD designations between 2013 and 2022. Multiple characteristics were analyzed, including the diseases targeted by RPD designation, whether the product targeted a neonatal disease, product type (drug/biologic), and the level of evidence (preclinical/clinical) to support designation. There were 569 RPD designations during the study period. The top therapeutic areas were neurology (26%, n = 149), metabolism (23%, n = 131), oncology (18%, n = 105). The top diseases targeted by RPD designation were Duchenne muscular dystrophy, neuroblastoma, and sickle cell disease. Neonatology products represented 6% (n = 33), over half were for drug products and 38% were supported by clinical data.ConclusionsThe RPD PRV program was created to encourage development of new products for children. The results of this study establish that a wide range of diseases have seen development—from rare pediatric cancers to rare genetic disorders. Continued support of product development for children with rare diseases is needed to find treatments for all children with unmet needs.

The Impact of the Priority Review Voucher on Research and Development for Tropical Diseases.

BackgroundIn 2007, the priority review voucher (PRV) was implemented in the US to incentivize research and development (R&D) for tropical diseases. The PRV is issued by the US FDA and grants a quicker review to manufacturers upon successful development of a product for a disease eligible for the program.ObjectiveThe objective of this analysis was to assess whether the PRV has incentivized R&D (measured as clinical trial activity) for the intended tropical diseases.MethodWe used a difference-in-difference-in-differences (DDD) strategy by exploiting variation in its implementation across diseases and registries around the world. Clinical trials were retrieved from the World Health Organization International Clinical Trials Registry Platform for the years 2005–2019.ResultsWe found a positive, but not statistically significant, effect of the PRV on stimulating R&D activity. Delayed effects of the policy could not be found.ConclusionOur findings, which were robust across a series of robustness tests, suggest that the PRV program is not associated with a trigger in innovation for neglected diseases and therefore should not be considered as a stand-alone solution. It should be supplemented with other government measures to incentivize R&D activity. To increase the value of the program, we recommend that the PRV only be awarded to novel products and not to products that have already been licensed outside the US. Doing so would restrict the number of vouchers awarded and slow down their ongoing market depreciation. Finally, we propose that product sponsors be required to submit an access plan for PRV-awarded products.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40290-022-00427-x.

​US Tropical Disease Priority Review Vouchers: Lessons In Promoting Drug Development And Access.

The COVID-19 global pandemic has devastated lives and economies. It has served as a reminder of how critical it is to invest in preventing and treating infectious diseases. Until the COVID-19 pandemic, the largest US government-sponsored reward for infectious disease drug and vaccine development was the Tropical Disease Priority Review Voucher program. Under this program, the Food and Drug Administration awards a priority review voucher to the sponsor of a new drug or vaccine for tropical infectious diseases. The voucher then can be exchanged for the faster review of one drug. We provide case studies for tropical disease voucher recipients between 2007 and 2018, examine the effects of the voucher program on product innovation and access, and recommend that policy makers protect the voucher program while creating complementary incentives.

Lassa virus diversity and feasibility for universal prophylactic vaccine.

Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, Mastomys natalensis, which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO’s TPP for an LASV vaccine.

Is the priority review voucher program stimulating new drug development for tropical diseases?

Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.

Expansion of the Priority Review Voucher Program Under the 21st Century Cures Act: Implications for Innovation and Public Health.

The U.S. federal government awards a priority review voucher (“PRV”) to a pharmaceutical manufacturer after the Food and Drug Administration (“FDA”) approves a product for one of a list of voucher-eligible indications. The voucher, which can be transferred or sold, allows the company to accelerate the review timeline of another product for any indication. The PRV program was proposed in 2006 as an incentive for research and development for neglected diseases, such as dengue and leishmaniasis.Neglected tropical diseases (“NTDs”) predominantly affect the world’s poorest populations and are associated with significant morbidity and mortality. Despite their global public health importance, neglected diseases were estimated to account for less than 1% of pharmaceutical research and development expenditures. The voucher program was intended to address this gap between investment and disease burden: “[t]he major obstacle to stimulating the R&D of new medicines for neglected diseases is lowincome nations' inability to pay for such medicines.” The voucher would provide an additional financial incentive to fund clinical development of these products without requiring additional appropriations from Congress.

Biosecurity Implications for the Synthesis of Horsepox, an Orthopoxvirus.

This article examines the biosecurity and biodefense implications resulting from the recent creation of horsepox virus, a noncirculating (extinct) species of orthopoxvirus. Here we examine the technical aspects of the horsepox virus synthesis and conclude that orthopox synthesis experiments currently remain technically challenging-and will continue to be so, even once this work is published in the scientific literature. This limits potential misuse by some types of nefarious actors. We also examine the implications of one stated purpose for the recreation of horsepox virus: the development of a smallpox vaccine. If the development is successful, it could take advantage of US government incentives for the priority FDA review of medical countermeasures (MCMs) against biosecurity threats. However, if this case leads to the determination that this incentive is counterproductive for security, the newly created priority review voucher program should be more clearly defined or limited based on need. Limiting the program could have costs that require further consideration, however, as general incentives for biodefense medical countermeasure development are required for MCMs to be available. Finally, while the recreation of horsepox virus was not technically trivial, nor was it cell-free, this experiment was a de facto demonstration of already-assumed scientific capabilities. The ability to recreate horsepox, or smallpox, will remain no matter what policy controls are put into place. It will be impossible to close off all avenues for nefarious misuse of gene synthesis, or misuse of biological materials more broadly. As a result, we advocate for the implementation of policy, regulations, and guidance that will make illicit recreation harder, more burdensome, more detectable, and, thus, more preventable without having sweeping negative consequences for the research enterprise. As part of our biosecurity efforts, we must also encourage and enable scientists to participate actively and to do all they can to safeguard their technical fields from irresponsible or illicit actions.

Association of the Priority Review Voucher With Neglected Tropical Disease Drug and Vaccine Development

This study uses commercial pharmaceutical database data to evaluate the number of new drugs and vaccines for neglected tropical diseases entering phase 1 clinical trials before and after introduction in 2007 of a priority review voucher program to incentivize development.

Strengthening the US Medical Countermeasure Enterprise for Biological Threats.

Strengthening the US Medical Countermeasure Enterprise for Biological Threats.

Obama extends program for rare pediatric drugs

President Barack Obama has signed into law a bill ( S. 1878) extending FDA’s rare pediatric disease priority review voucher program through the end of the year. The biotech industry, which strongly supports the program, is urging lawmakers to include a multiyear extension in the 21st Century Cures Act, a sweeping piece of health care legislation that is being negotiated by the House of Representatives and the Senate. The rare pediatric disease program awards a voucher to a drugmaker that wins approval of a treatment for an illness affecting 200,000 or fewer children. The company can later redeem the voucher when seeking approval for another medicine to treat any illness. FDA is obligated to review the other drug in six months instead of the standard 10 months. The Biotechnology Innovation Organization, an industry trade group, calls the voucher program “a critical incentive in promoting research into rare diseases affecting children.”

Priorities for the Priority Review Voucher

The U.S. Congress created the priority review voucher program in 2007 to encourage development of drugs for neglected diseases. Under the voucher program, the developer of a drug for a neglected or rare pediatric disease that is approved by the U.S. Food and Drug Administration receives a bonus priority review voucher for another drug. As of 2016, four vouchers have sold for an average price of $200 million. Recent experience with the voucher program indicates strengths and weaknesses of the program, as well as a need for legislative changes.

Analyzing the FDA Priority Review Voucher Program's Stimulation of Research and Public Health Impact

Priority Review Vouchers are FDA incentive programs for stimulating research into rare pediatric and neglected tropical diseases. Upon successful approval of a new drug application or new biologic license application for a target rare/neglected disease, the sponsor is awarded a voucher. This voucher may then be applied to shorten the review time of any subsequent drug/biologic application. The voucher can also be sold for use by another drug sponsor. These programs have been controversial and subject to criticism. In order to supplement current reviews of the programs, we have undertaken a quantitative analysis of the programs’ efficacy. Through interviews and examination of available data, we have observed an increase in drug approval, significant interest in the intended research areas as well as some modest investment since program establishment. Despite the increase in the use of these vouchers, there is no evidence of a decrease in the FDA’s ability to respond to drug applications in a timely manner. Taken together, we conclude that the programs appear to be on track to stimulate research and development for the targeted rare/neglected indications. Because of the long cycle of drug development, more time is needed before a conclusion can be made on whether the programs have met their stated goals. Finally, we offer suggestions for improvement to the program. Keywords: Priority Review Voucher, PRV, Rare Pediatric Disease, Neglected Tropical Disease, FDA Incentive.

The Commercial Market For Priority Review Vouchers.

In 2007 the US Congress created the priority review voucher program to encourage the development of drugs for neglected diseases. Under the program, the developer of a drug that treats a neglected disease receives both a faster review of the drug by the Food and Drug Administration and a voucher for a faster review of a different drug. The developer can sell the voucher. We estimated the commercial value of the voucher using US sales of new treatments approved in the period 2007-09. A third of the commercial value of a voucher comes from capturing market share from competitors, nearly half from the value of earlier sales because of the expedited review, and less than a quarter from lengthening the time between approval and the launch of a generic competitor. We estimate that if only one priority review voucher is available in a year, it will be worth more than $200million, but if four vouchers are available, the value could fall below $100million. Congress should be cautious about expanding the voucher program, because increasing the number of vouchers sharply decreases the expected price. Lower voucher prices could undermine the incentive to develop new medicines for neglected diseases.

Experience With the Priority Review Voucher Program for Drug Development.

Experience With the Priority Review Voucher Program for Drug Development.

New regulatory paradigms for innovative drugs to treat pediatric diseases.

New regulatory paradigms for innovative drugs to treat pediatric diseases.

The Impact of the US Priority Review Voucher on Private-Sector Investment in Global Health Research and Development

Diseases such as trypanosomiasis, leishmaniasis, and lymphatic filariasis impose substantial health burdens in developing countries [1], [2]. These diseases are widely neglected because there is little financial incentive for biopharmaceutical companies to invest in developing new treatments, vaccines, and diagnostics. Most of the 1,000,000,000 people affected by neglected diseases are poor and live in low-income countries [3]. Although there is a significant need for new cost-effective drugs and vaccines, from 1975–1999 less than 1%–2% of new chemical entities marketed were for tropical diseases and tuberculosis [1], [4]. Market incentives play an important role in mobilizing companies toward neglected tropical disease (NTD) research. Pharmaceutical companies have a fiduciary responsibility to shareholders to maximize profits. Absent of other incentives, companies will focus research and development (R&D) on products and programs that possess a profitable market, have a sufficient likelihood of technical success, and are likely to achieve a maximum return on investment. In contrast, the global burden of neglected infectious diseases is concentrated in developing countries with inadequate health budgets and poor patients who can pay only low prices for drugs, if they can afford to pay at all. Drugs and vaccines that target neglected diseases thus typically cannot compete with potentially profitable products for internal company or investor R&D dollars. Governments and foundations have recognized the dearth of private-sector incentives for investment in NTD research and have responded with “push” funding (up-front funding for drug development) and “pull” mechanisms (rewards for output) to promote successful development [5], [6]. The priority review voucher (PRV) program, currently administered by the US Food and Drug Administration (FDA), was passed into United States law in 2007 as a pull mechanism to help promote R&D for new medicines targeting NTDs, malaria, and tuberculosis [7]. Under this law, companies that receive FDA approval for a novel drug or vaccine targeting one of 16 tropical diseases are awarded a transferable voucher. This voucher can be sold to a second organization or can be redeemed to grant the bearer priority six-month review for a future medicine of their choosing [8]. As average standard review periods can range between 10–16 months, the voucher could potentially allow drugs to reach the market up to eight months earlier. Economic models have predicted that this faster time to market could be worth between US$50 million to US$300 million [9], [10]. However, the impact of the PRV incentive in developing new medicines for NTDs has been questioned, in part due to uncertainty around the value of the voucher among pharmaceutical and biotech companies [11], [12]. The PRV program as implemented carries restrictions that make earning or using a voucher difficult or impractical, such as a requirement that developers provide notice to the FDA at least one year prior to the use of a voucher (often before clinical trials have concluded). Further, the voucher has not resulted in demonstrated value for any company to date. At writing, Novartis is the only company to have received a PRV, which they used in 2011 to accelerate the review of a supplemental new drug application (sNDA) for their gouty arthritis drug candidate Ilaris (canakinumab) [13]. The FDA fulfilled their responsibilities under the PRV program to conduct a six-month priority review, but ultimately denied approval of Ilaris citing the need for further data to assess the overall safety profile [14]. It is possible that Novartis gained some benefit from the use of the PRV for the review of Ilaris, but this value is difficult to quantify.

Accelerating drug development and approval

Regulatory agencies are the gateway between the pharma/biotech industry and patients and can serve as stimulators of new drug development. This article highlights several means of doing so implemented thus far, many with already impressive histories, such as orphan drug legislation, and others of a more experimental nature, such as the FDA's priority review voucher program. These initiatives represent different approaches to finding treatments for rare and widespread but neglected diseases, as well as speeding the development process for pharmaceutical and biological agents more generally. Commercial incentives, streamlined regulatory processing, exploratory trial designs, research assistance and cash infusions are all means of promoting drug development being explored in the United States, Europe and beyond. In some cases, such as fast track designation and priority review vouchers, regulatory agencies have turned their own processes into incentives, offering advantageous alternative routes to product approval, like a faster lane on the highway for vehicles carrying multiple passengers. In 2009, regulatory agencies and the governments they represent also had to confront two tremendous challenges: the global recession and the H1N1 influenza virus pandemic. These tests have been met with increased funding in the former case and coordinated efforts to develop, approve and stockpile H1N1 vaccines in the latter.