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

Abstract

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.

Congress created the priority review voucher in 2007 to incentivize the development of treatments for neglected tropical diseases. Vouchers, which can be transferred or sold, are awarded when a company obtains US Food and Drug Administration (FDA) approval for a drug or vaccine indicated for a neglected tropical disease (Box). They allow sponsors to obtain faster FDA review of a product for any indication, not restricted to neglected tropical diseases, moving the application from the standard 10 months to the priority review timeline of 6 months. This provides valuable earlier access to the US market for those drugs that would have not otherwise qualified for priority review: vouchers have been sold for prices ranging from $67 million to $350 million.

Box. Criteria for Neglected Tropical Disease Priority Review Voucher Eligibility.

1. Provision of treatment or vaccination of 1 of the following diseases^a:

   • Blinding trachoma

   • Buruli ulcer

   • Chagas (added 2015)

   • Cholera

   • Dengue

   • Dracunculiasis

   • Fascioliasis

   • Filovirus (added 2014)

   • Leishmaniasis

   • Leprosy

   • Lymphatic filariasis

   • Malaria

   • Neurocysticercosis (added 2015)

   • Onchocerciasis

   • Schistosomiasis

   • Soil-transmitted helminthiasis

   • Trypanosomiasis

   • Tuberculosis

   • Yaws

   • Zika virus (added 2016)

2. Submission to the US Food and Drug Administration as a new drug application or biologics license application

3. Novel drug or biological product (no active ingredient of the drug, including any ester or salt of the active ingredient, may have been approved in any other application)

4. Qualification of a drug or vaccine for priority review on its own merit

Since 2007, only 4 neglected tropical disease vouchers have been awarded. To our knowledge, no one has investigated whether the use of priority review vouchers may have had the intended effect on incentivizing development of drugs and vaccines for neglected tropical diseases. This study evaluated the number of new drugs and vaccines for neglected tropical diseases entering phase 1 clinical trials before and after the voucher incentive was created.

Methods

We identified all compounds entering phase 1 trials between January 2000 and December 2014 using Pharmaprojects, a large commercial database of global pharmaceutical research and development (Informa) that is widely used by researchers, regulators, and industry to track drug development trends. This database is one of the most comprehensive of its kind and compiles public and proprietary information about investigational drugs throughout their lifecycle, including press releases, regulatory filings, investor reports, scientific literature, and direct communication with companies. We cross-checked information on trial start dates with AdisInsight (Springer), 1 of the 2 other major commercial databases.

We identified voucher-eligible new drugs and biologics with qualifying indications entering phase 1 trials. To compare trends before and after voucher program creation, a Poisson model was fit that included the count of neglected tropical disease drugs each year as the dependent variable and variables for year before and after 2007 (year of voucher program creation) as the independent variables. The log of the total number of drugs each year was included as a model offset, so that parameters could be interpreted as rate ratios, in which the rate was the proportion of neglected tropical disease drugs each year (R [R Foundation], version 3.3).

Results

Between 2000 and 2007, 32 novel products intended to prevent or treat neglected tropical diseases started phase 1 trials (1.9% of 1704 phase 1 trials), vs 34 products between 2008 and 2014 (1.5% of 2302 trials) (Figure). The proportion of neglected tropical disease drugs among all products in development decreased by 1.74% per year (95% CI, −13.68% to 12.87%) before the voucher was created and decreased by 1.73% per year (95% CI, −12.75% to 10.27%) after the voucher was created.

Figure. Neglected Tropical Disease Phase 1 Trial Initiation, 2000-2014.

Congress created the priority review voucher in 2007 to incentivize the development of treatments for neglected tropical diseases. The number of voucher-eligible pharmaceutical products entering phase 1 trials was identified for each year from 2000-2014. The Figure shows trend lines fit to the data separately for the years 2000-2007 and 2008-2014. For 2000-2007, the mean No. of voucher-eligible pharmaceutical products entering phase 1 trials per year was 4 (median, 4.5 [range, 1 to 6]). For 2008-2014, the mean No. of voucher-eligible pharmaceutical products entering phase 1 trials per year was 4.9 (median, 5 [range, 2 to 7]). The percentage of new neglected tropical disease drugs is the proportion of all phase 1 trials for drugs with a neglected tropical disease indication. This proportion decreased by 1.74% per year before 2007 (95% CI, −13.68% to 12.87%) and decreased by 1.73% after 2007 (95% CI, −12.75% to 10.27%).

Discussion

The priority review voucher was not associated with an increase in innovative, early-stage neglected tropical disease product development. Although this analysis did not examine whether the voucher encouraged companies to move compounds already in clinical development into phase 2 and phase 3 trials, any such products would likely have completed development in the last 9 years. The paucity of approved neglected tropical disease products in the last decade suggests the voucher also did not serve as a stimulus for stalled late-stage development. The assessments of novelty used in this analysis were based on publicly available information and may differ from the FDA’s determination.

Companies may not have responded to the voucher incentive because its value is uncertain: the value decreases as more vouchers become available on the market. Since 2007, Congress has expanded the number of voucher programs so that vouchers can now also be awarded for new treatments for rare pediatric diseases and medical countermeasures. An improved incentive scheme would reduce the risk of neglected tropical disease product development such as by decreasing the cost of clinical trials to pharmaceutical companies. A public-private partnership could provide financial support to sponsors of neglected tropical disease products. The partnership could be actively managed to ensure reasonable cost and access to the end product, unlike the priority review voucher, which does not require companies to make products widely available to patients.

Section Editor: Jody W. Zylke, MD, Deputy Editor.