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

Abstract

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.