The Program Stimulating Research Into Tropical and Rare Pediatric Diseases

The priority review voucher (PRV) program was designed to incentivize development for drugs treating diseases that otherwise would be unlikely to attract interest from manufacturers.

The program was first signed into law in 2007 to provide the reward of an additional priority review (beyond the drug that earned the PRV) for a manufacturer that has acquired FDA approval for a drug treating a neglected tropical disease. The program was expanded to include rare pediatric diseases in 2012.

Neglected tropical diseases are found primarily in developing countries where many patients are unlikely to be able to afford expensive drugs, while pediatric rare diseases have low patient populations. In both cases it was thought that drugs used to treat these diseases would not be profitable for their developers.

A PRV can be applied to another new drug application (NDA) or biologics license application (BLA) in the future that would not otherwise qualify for a priority review. For example, a manufacturer earns a PRV for gaining approval for a drug treating dengue. They could apply that PRV to a different non-novel drug treating hypercholesterolemia (that likely wouldn’t merit priority review on its own) being submitted for FDA review. The PRV can be used for another one of the manufacturer’s pipeline drugs or it may be sold to another manufacturer who is interested in having their own drug reviewed by the FDA in 6 months._¹

How Have PRV’s Been Used?

Manufacturers of 11 products have been awarded PRV’s since the program started and they have proven to be valuable assets. Four are known to have been sold with prices ranging from $67.5 to $350 million. Selling PRV’s may be an appealing option to smaller manufacturers who could be more likely to benefit from additional funds than to have another pipeline drug in development that would benefit from a faster FDA review.

Praluent® (alirocumab) and Odefsey® (emtricitabine + rilpivirine + tenofovir alafenamide) each came to market after their manufacturers redeemed a PRV. Additionally, 5 awarded PRV’s have not yet been used.²

Potential Drawbacks to the PRV Program

While the PRV program may appear to be a win-win situation for all involved, there are some potential drawbacks associated with it that may be less obvious.

There is an additional burden on the FDA to perform a priority review for a drug that would not ordinarily merit one and the FDA claims that expedited timeline can be difficult to meet. While the FDA does have to work under tighter timelines to perform a priority review, they are regularly awarded. In fact, 24 of the 45 (53%) of novel new drugs approved in 2015 were granted priority review by the FDA.² If priority reviews are overly taxing on the FDA, it would be sensible to tighten the criteria for earning one.

It is difficult to prove that the PRV incentive is achieving its intended purpose. Is the PRV incentive what led manufacturers to develop drugs for rare pediatric and neglected tropical diseases or would they have done so otherwise given that there are other orphan drug development incentives such as market exclusivity and tax breaks?

Partly due to the lengthy nature of drug development , the US Government Accountability Office concluded that it was too early to gauge the effectiveness of the rare pediatric disease PRV program.³ However, at least 2 leaders at different manufacturers have written to the innovators of the PRV program to explain how it encouraged their company in the development of treatments for neglected tropical diseases.⁴

The PRV program should continue to be evaluated for how well it accomplishes the goal of incentivizing drug development for rare pediatric and neglected tropical diseases. It likely will be difficult to measure quantitatively, but as more time goes by we will perhaps have a better picture of its efficacy.

Drug costs are a serious concern in the United States and orphan drugs are among the most expensive treatments. There may be concern that the PRV program is providing an additional reward to manufacturers that is not deserved. However, it would be unfortunate to lump the PRV program into the broader problem of drug cost. The issue of drug cost goes well beyond the PRV program and deserves attention as a separate, and more complex, issue.

What Happens to the PRV Next?

The rare pediatric disease portion of the PRV program was scheduled to expire at the end of September 2016. However, President Obama signed a bill to extend the program by 3 months, presumably for further evaluation and possible adjustment.^₅.

The ideas behind the PRV voucher program are laudable. New treatments becoming available for rare pediatric or neglected tropic diseases and rewarding manufacturers for their development is a positive thing. Instead of letting the PRV program expire, the most sensible course of action would be to make modifications to the program to address some of the concerns and monitor it for long term efficacy as best as possible.

References

1. Regulatory Affairs Professionals Society. “Regulatory Explainer: Everything you need to know about FDA’s priority review vouchers.” http://www.raps.org/Regulatory-Focus/News/2015/07/02/21722/Regulatory-Explainer-Everything-You-Need-to-Know-About-FDA%E2%80%99s-Priority-Review-Vouchers/. Accessed November 17, 2016

2. US Food and Drug Administration Center of Drug Evaluation and Research. Novel Drugs 2015 Summary.

3. US Government Accountability Office (GAO). “Rare diseases: too early to gauge the effectiveness of FDA’s Pediatric Voucher Program”. GAO Website. http://www.gao.gov/products/GAO-16-319. Accessed November 17, 2016.

4. Priority Review Voucher. http://priorityreviewvoucher.org/. Accessed November 21, 2016.

5. FDA Law Blog. The Official blog of Hyman, Phelps, & McNamara, P.C. “Pediatric priority review vouchers saved in the eleventh hour." http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2016/10/pediatric-priority-review-vouchers-saved-in-the-eleventh-hour.html. Accessed November 17, 2016.