Analysis of Neglected Tropical Disease Drug and Vaccine Development Pipelines to Predict Issuance of FDA Priority Review Vouchers over the Next Decade

Abstract

The need for new drugs and vaccines for neglected tropical diseases (NTDs) is widely accepted [1]. Yet, encouraging pharmaceutical and biotechnology company investment in developing these much-needed treatments remains a challenge due to a lack of a commercial market driving companies to pursue NTD projects [2]. To address this challenge, economists Ridley, Grabowski, and Moe at Duke University conceived of an incentive to encourage investment in the development of new drugs and vaccines for NTDs: the US Food and Drug Administration's (FDA) priority review voucher (PRV) program [3]. The program was signed into law on September 27, 2007 [4], and went into effect one year later. Under the program, the FDA awards a voucher to the sponsor of a newly approved drug or vaccine that targets an NTD (such as cholera or dengue) or malaria and tuberculosis (TB). The voucher, which can be traded or sold, entitles the holder to a 6-month priority review for a future new drug application that would not otherwise qualify for priority review—potentially shaving between 4 and 12 months from the standard FDA review process [5]. Since the program's inception, only one PRV has been awarded, to Novartis Pharmaceuticals Co. for their 2009 approval of the antimalarial drug Coartem. Novartis used the voucher to accelerate the review of one of its own products, rather than selling it on the marketplace. Because a product resulting from a PRV has not yet been sold in the marketplace, the value remains uncertain. Early economic models estimated that the worth of a PRV could range from US$50 million to US$500 million, with an average value of US$322 million, and a variation in value based on the therapeutic area for which it is used [5], [6]. Part of predicting the value relies on the supply and demand of vouchers; that is, will the number of vouchers awarded be absorbed by the blockbuster products that are likely to be the intended recipients of benefit from accelerated review? The lack of understanding as to how many PRVs may be awarded in the future limits companies from predicting the potential value of a voucher that might be earned. In the absence of a tangible example of a voucher's market value, companies, the FDA, policymakers, and other program stakeholders could benefit from examining NTD product pipelines, understanding when the next PRV(s) are expected to be issued, and ultimately quantifying the supply side of the PRV market. In addition, it is unclear to global health stakeholders whether companies are actively pursuing PRV-eligible products, and if they are, whether the PRV incentive has had an impact on their motivation [5], [6]. Here, we present an analysis of the drug and vaccine development pipeline to a) identify products that meet eligibility criteria to earn a PRV, and b) predict the number of PRVs that will be issued over the next 10 years. Of those products currently in clinical development, standard industry probabilities of success (POS) were applied to predict how many drugs and vaccines will ultimately earn regulatory approval, and therefore a PRV. Presumably, if stakeholders are armed with a supply forecast of the PRV market over the next decade, companies can conduct more informed calculations of value estimates, policymakers can assess whether the demand market for PRVs absorbs those vouchers being awarded, and the FDA can more accurately predict their expected workload increases when the PRVs are used.