Priority Review Vouchers Raise Risks, say FDA Officials

December 29, 2015

Jill Wechsler on why the FDA program that encourages biopharma companies to develop new treatments for rare and neglected diseases has been in the spotlight recently.

The FDA program that encourages biopharma companies to develop new treatments for neglected tropical diseases and rare pediatric disorders has been in the spotlight recently, as pharma companies have bid up prices on the program’s accompanying vouchers that offer a speedier review of a new drug application.

Priority review vouchers (PRV) have strong support from the rare disease community and international health authorities in hopes that it will spur development of needed new therapies. In the recently approved omnibus budget bill, Congress reauthorized the pediatric rare disease voucher program through next September, preventing it from sunsetting in March.

But many FDA officials object to the PRV program because it compromises their ability to decide which drug candidates warrant a priority, six-month review (vs. the usual ten months), based on a new drug’s breakthrough, orphan drug status, or potential to address an unmet medical need. Even though PRVs are awarded to developers of qualifying treatments for rare conditions, they can be applied to any new drug application (NDA), and FDA is obliged to speed up its oversight process, even for what it considers a conventional therapy. PRVs are worth millions to sponsors of potential blockbuster drugs, and the purchase prices have been increasing. One voucher recently sold for $350 million, and Sanofi recently filed an NDA for a new fixed-dose combination diabetes treatment, along with a PRV purchased for a total $245 million; Sanofi hopes to gain market approval for its diabetes treatment before competitors, as it did last year with its new PCSK9 inhibitor for high cholesterol.

The program also has drawn fire by awarding PRVs to biopharma companies that gain FDA approval of drugs long-used to treat tropical diseases in developing countries, but never marketed in the US‑ actions that don’t really meet the aim of stimulating R&D on new medicines. Before his recent indictment, former Turing CEO Martin Shkreli bragged that through his acquisition of drug maker KaloBios, he would seek FDA approval of a widely used treatment for Chagas disease in order to gain a PRV that he then could sell for millions.

Faulty Principles

Being required to conduct a speedy review of an application that may not be suitable for fast scrutiny and approval, which draws strong objections from some FDA officials. At the FDA/CME Summit in December 2015, John Jenkins, director of the Office of New Drugs (OND) in the Center for Drug Evaluation and Research (CDER), described the priority review voucher concept as “built on faulty economic principles.”

While Jenkins supports the overall goal of providing incentives for manufacturers to develop new therapies to treat tropical diseases and rare disorders, he objects to being obliged to provide an accelerated review for a new therapy that may raise important safety and efficacy issues.

“You can’t magically change the risk profile of a standard drug,” he told this reporter, noting that reviewers often have to address complex issues, and that rushing a review could lead to errors. The program’s entire premise is “wrong,” he said; “We’re not making pizza here.”

And in offering FDA’s limited resources to the highest bidder, Jenkins fears that could create situations which heighten the perception of FDA being in “industry’s pocket.”