FDA Clarifies Its Rare Pediatric Disease Priority Review Voucher Program

By Alexander J. Varond & Anne K. Walsh –

On November 17, 2014, FDA announced the availability of its draft guidance entitled, “Rare Pediatric Disease Priority Review Vouchers.” The draft guidance “is intended to assist developers of rare pediatric disease products in assessing whether their product may be eligible for rare pediatric disease designation and a rare pediatric disease priority review voucher.” Earlier this year, FDA had announced its intention to release the draft guidance as part of a larger effort to clarify issues related to pediatric drug development.

We posted here an in-depth discussion of the Rare Pediatric Disease Priority Review Voucher (“Pediatric PRV”) program in comparison to the earlier implemented Tropical Disease PRV program.  As a short recap, the Pediatric PRV program was created in 2012 to encourage development of treatments for rare pediatric diseases. (See our FDASIA summary at pages 54-56). A Pediatric PRV is granted to the sponsor of a qualifying approved “rare pediatric disease product application.” The voucher can be sold (without limitation), and the holder of the voucher can redeem it with a subsequently filed NDA or BLA, requiring FDA to meet the review goals for a priority review, versus a standard review.

To qualify to receive a Pediatric PRV, a sponsor must submit an application for a drug or biologic intended to prevent or treat a rare pediatric disease.  Such drug or biologic may not contain any active ingredient (including any ester or salt of the active ingredient) previously approved in any drug or biologic application.  The rare pediatric disease application also must be eligible for priority review (e.g., an application for a drug that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness) and rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population.

FDA’s draft guidance “clarifies the process for requesting [Rare Pediatric Disease] designations and vouchers, sponsor responsibilities upon approval of a rare pediatric disease product application, and the parameters for using and transferring a rare pediatric disease priority review voucher.” It is written in a Q&A format, and its questions range from the basic (e.g., “What is a priority review voucher and when is it awarded?”) to the more complex (e.g., “What does ‘Does not seek approval for an adult indication in the original rare pediatric disease product application’ mean?” or “Will a drug that receives rare pediatric disease designation also qualify for orphan-drug designation?”). In general, the draft guidance reiterates much of what was already contained in Section 908 of the FDASIA.

Nevertheless, the draft guidance is useful in that it:

• Interprets the term “rare pediatric disease” to mean “if the entire prevalence of the disease or condition in the U.S. is below 200,000 and if more than 50% of patients with the disease are 0 through 18 years of age. Another way a drug may qualify as a drug for a ‘rare pediatric disease’ is if it is for an ‘orphan subset’ of a disease or condition that otherwise affects 200,000 or more persons in the U.S., and if this subset is primarily (i.e., more than 50%) comprised of individuals aged 0 through 18 years.”
• Describes the rare pediatric disease designation process.
• Clarifies that the designation is not a prerequisite to requesting or receiving a priority review voucher.
• Details the information that should be included in the designation requests.
• Explains how sponsors should calculate prevalence estimates, breaking down the differences in estimating prevalence for therapeutic drugs and for vaccines, diagnostic drugs, and preventative drugs.
• States the terms for transferring the Pediatric PRV, for notifying FDA, and for redeeming the voucher with a subsequently filed application.

This guidance comes at an ideal time. Just two days after its publication, on November 19, 2014, Knight Therapeutics Inc. announced that it had sold its Tropical Disease PRV for $125 million to Gilead Sciences, Inc. The Tropical Disease PRV program is designed differently than the Pediatric PRV program, but the incentive program operates similarly. Gilead’s purchase nearly doubles the $67.5 million price paid in July 2014 by Sanofi and Regeneron for BioMarin Pharmaceutical Inc.’s Pediatric PRV. Perhaps these recent sales will provide further incentive to companies to develop drugs to treat rare pediatric diseases or tropical diseases, an outcome which Congress anticipated.

In addition, both the House and Senate are quickly moving toward a vote on legislation that would modify the Tropical Disease PRV program to include Ebola as a disease eligible for a Tropical Disease PRV and make the benefits of the program more favorable. If enacted, the legislation would remove the current limit on the number of times a Tropical Disease PRV can be transferred and reduce the notification time required to use the Tropical Disease PRV from one year to 90 days.