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W-30: Analysis of Products Awarded the Rare Pediatric Disease Priority Review Voucher and the Impact of Advancing Hope Act

Poster Presenter

Caitlin Wolf Skenyon

Regulatory Strategy
Alnylam Pharmaceuticals
United States

Objectives

The Rare Pediatric Disease Priority Review Voucher (RPDRV) program was amended by the Advancing Hope Act (AHA) in 2016. This analysis characterizes applications awarded by the RPDRV and trends in applications approved before and after implementation of the amendment.

Method

A systemic database search of the Federal Register was conducted to identify products granted an RPDRV. Using the Drugs@FDA database, New Drug Application (NDA) reviews for each drug were analyzed for prespecified characteristics: approved indication, patient population, and pediatric enrollment.

Results

From the initiation of the RPDRV program in 2014, a total of 17 products have been awarded a voucher. One third (n=6) of these products are chemically synthesized drugs, two-thirds (n=10) are biologics, and one is a gene therapy. Nine vouchers have been sold to subsequent pharmaceutical companies, of which six vouchers have been used to successfully commercialize a product. Three products received Rare Pediatric Disease Designation prior to receiving the voucher. The majority of products (n=13) received approval by the FDA first, while three products were approved by the European Medicines Agency (EMA) a few months prior to the US. One product was available outside of the US for 32 years. Three products were indicated for disease states in which FDA approved treatments were already available. Eleven products included adult populations in the indication. Most of the recipients (n=11) had Phase 3 clinical trials that restricted enrollment to only pediatric patients. One product excluded pediatric patients from Phase 3 trials. Prior to the AHA implementation in September 2016, seven products were awarded an RPDRV and ten products received a voucher after. Before the AHA, 28% (n=2) of the approved products had a specified indication in pediatric populations. Nine (90%) products had Phase 3 trials with 100% enrollment of pediatric patients, except for one trial that had enrolled 79.5% pediatric patients of the total enrolled group. After the AHA, 100% (n=10) of the labels approved included pediatrics indications and 60% (n=6) of Phase 3 trials had 100% enrollment of pediatric patients. Trials that enrolled adult patients in addition to pediatric patients enrolled 43-66% pediatric patients. The number of products that received breakthrough designation or priority review in addition to an RPDRV increased after the AHA, from 29% (n=2) and 57% (n=4) to 50% (n=5) and 60% (n=6), respectively. The duration of the trials shortened after the AHA from 175 weeks to 36 weeks.

Conclusion

The aim of the RPDRV Program is to incentivize drug development for rare diseases in pediatric populations which have been historically underserved due to the complicated nature of drug development in these patients. Vouchers granted under this program are transferrable, allowing a sponsor to utilize priority review for their own application or sell to another sponsor. Vouchers have been sold for up to 130 million USD. Over time, the price of the vouchers has fluctuated to as low as 67 million USD. However, the value of the sold voucher is not always disclosed. A primary criticism of the voucher program is that products previously approved in other countries gain unnecessary incentive to apply for approval in the US market. While this remains a concern, there does not appear to be a trend, as only one of the 18 products was available for decades prior to approval in the US. Other products were commercialized in the European Union within months FDA approval. The implementation of the Advancing Hope Act strengthened the definition of rare pediatric disease by specifying that the condition must be serious or life-threatening and primarily affecting patients less than 18 years old. This is verified by the approved indication statements in product labels post-AHA, as all products obtaining a voucher during this time had a specified use in pediatric populations. Furthermore, the duration of the Phase 3 trials for these products shortened significantly after the AHA. This is most likely due to the increase in priority review and breakthrough designations granted to these products. There was a significant increase in the number of RPDRVs awarded after the AHA, which demonstrates a growing interest in the voucher programs. The results of this study were dependent on the availability and consistency of information provided in FDA reviews, which had varied over time.