FDA's Priority Review Voucher Program Not Spurring Drug Development as Intended

In 2007, Congress approved a program to help overcome barriers to development of drugs that treat conditions disproportionately affecting poor people in developing countries. The program offers priority review vouchers (PRVs) to companies that sponsored newly approved medications to treat qualifying neglected tropical diseases such as tuberculosis (TB), malaria, schistosomiasis, and yaws. Once awarded, PRVs can be sold or transferred or redeemed at the FDA to accelerate the regulatory review of a different product from the standard 10 months to a priority 6-month period meant for drugs that appear to represent a therapeutic advance. In 2012 the program was expanded to cover sponsors of FDA-approved drugs treating rare pediatric diseases.

In recent JAMA Viewpoint opinion article, Aaron S. Kesselheim, MD, JD, MPH, and colleagues at Harvard Medical School analyzed the experience with the PRV program to date. Through August 6, 2015, the FDA has issued 6 PRVs:

• 2009: To Novartis for antimalarial artemether-lumefantrine
• 2012: To Johnson & Johnson for bedaquiline for multidrug resistant TB
• 2014: To Knight Therapeutics for miltefosine for leishmaniasis
• 2014: To BioMarin for elosulfate alfa for rare pediatric syndrome
• 2015: To Asklepion for cholic acid for rare pediatric single-enzyme defect
• 2015: To United Therapeutics for dinutuximab for pediatric neuroblastoma

In most of the 6 cases in which PRVs were awarded, vouchers were sold or used to accelerate FDA reviews of other, non-pediatric and non-tropical, disease-treating drugs. Based on this experience, Dr Kesselheim and his colleagues have concluded that there is little reliable evidence that the program’s primary intention of spurring novel drug development has been met, at least for tropical diseases, for which PRVs have now been available for 7 years.

The authors cite the following evidence: artemether-lumefantrine had been registered worldwide prior to FDA approval; miltefosine was registered outside the US a decade before its FDA review and the sponsor who got the voucher was not involved in its development; and artemether-lumefantrine, miltefosine, dinutuximab, and cholic acid were all created based on significant public sector investment.

Although the value of a PRV has increased from $67.5 million to $350 million, the authors say, even $350 million 10 years in the future is not enough for large pharmaceutical manufacturers to change their investments to tropical or rare pediatric disease.

The PRV program may have had a limited influence on drug development because its value only accrues after drug approval, the authors say.

“One way to potentially prevent such windfalls would be to redesign the voucher system so drug companies would have to show some level of investment in a new drug’s development before earning the reward,” they suggest.

Furthermore, the vouchers are not ensuring affordable access to the products in the US or abroad, and the authors therefore suggest making use or sale of the voucher conditional upon demonstrating equitable marketing of the drug.

Several more promising approaches exist to promote discovery of new treatments for neglected tropical diseases or other overlooked disease classes, Dr Kesselheim and colleagues conclude, such as greater funding of basic science research to help identify novel targets for therapy.