Exploring the FDA's Tropical Disease Priority Review Voucher

The neglected tropical disease priority review voucher (PRV) program has helped fast-track several drugs for US Food and Drug Administration (FDA) approval, improving outcomes for those infected with malaria and tuberculosis, among others.

As concerns over the spread of tropical infectious diseases increase, in the age of Zika virus and Dengue fever in particular, PRVs may have significant implications for the development of novel vaccines and antivirals, assuming the program is used effectively. In a perspective piece published in the January issue of The American Journal of Tropical Medicine and Hygiene (AJTMH), Jonathan Berman, MD, PhD, and Tanya Radhakrishna debate the merits of the federal program, based on its implementation to date.

“In favor of the program is that, at no cost to the US taxpayer and without impact on FDA review of other products, tropical disease products are available for US use, and increased confidence is generated for the product worldwide from an intense FDA clinical and manufacturing review and from [postmarketing requirement]-generated data,” they write. However, they add, “it may be difficult to decide whether the advantages of the PRV program outweigh the disadvantages or vice versa.”

According to Dr. Berman, senior vice president, Clinical Affairs at North Potomac, Md.-based Fast Track Drugs and Biologics, LLC, a contract research organization that provides strategic planning, clinical trial, and regulatory support services to pharmaceutical and biotech companies, and Radhakrishna, director, Business Development at Montreal-based Knight Therapeutics, a specialty pharmaceutical company, the PRV program was enacted into law by Congress in 2007 as part of a new section of the Federal Food, Drug, and Cosmetic Act. It effectively “provides financial incentives for sponsors of tropical disease products.” The authors note that sponsors must be approved for a new drug application or biologics licensing application (BLA) for a new chemical entity “that constitutes a significant improvement for one of at least 16 listed tropical diseases” prior to applying for PRV, which fast tracks the process for any subsequent new drug application and/or biologic licensing application as a “priority review.” A priority review usually cuts the FDA review period from 10 months to 6 months.

Of particular concern to some within the industry, PRVs are transferrable, and have been sold for fees in excess of $300 million from company to company as the products for which they have been granted have changed hands. In some cases, they write, the return on investment for PRVs “may… be viewed [either] as acceptable or excessive.” For example, according to Dr. Berman and Ra Radhakrishna dhakrishna, the pharmaceutical company Retrophin received $245 million for the voucher for cholic acid, for which it invested $79 million, while Paladin/Knight received $125 million for the tropical disease voucher for miltefosine, for which it invested $12 million.

Despite these debatable shortcomings, in recent years, Congress has added Ebola/filoviruses and the FDA has added Chagas disease and neurocysticercosis to the list of PRV-eligible diseases. Moreover, last year, as part of a related program for rare pediatric diseases, a PRV was awarded for Vaxchora, a vaccine against Vibrio cholerae serogroup O1.

“With these actions, the US government, at least, is viewing the neglected tropical disease PRV program positively,” Dr. Berman and Radhakrishna write.

According to the authors, to qualify for a PRV, a drug must be a new chemical entity, rather than a “new ether of an already-approved drug… [or] new indication for a previously approved drug.” Furthermore, any product for which a company is applying for a PRV must have sufficient clinical trial data for the FDA, supporting its safety and efficacy as well as its therapeutic value over currently available products. This, Dr. Berman and Radhakrishna note, is “defined as increased effectiveness, substantial reduction of a treatment-limiting drug reaction, enhancement of patient compliance, or safety and effectiveness in a new subpopulation.” Notably, they add, companies can only apply for PRV once a new-drug/biologic-licensing application has been approved.

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.