«

»

Feb 12 2013

Everything You Need to Know About Priority Review Vouchers: Part 1 of 2

The Basics, History, and Record of the Priority Review Voucher Program

The Basics

PRV Coupon - Pt1If your company’s goals include funding pipeline development or increasing speed to market you should, at least, be familiar with the concept of the Priority Review Voucher (PRV). A PRV would be aptly described as an obscure or esoteric regulatory curiosity by even the most seasoned drug development professional.  But despite the PRV’s poorly understood, and at times maligned nature, drug developers both big and small will be well served to educate themselves on the existence and nuances of the PRV.

If the idea of a coupon that grants the bearer a 6-month priority review by the FDA doesn’t intrigue you, the estimated, and much debated, value of $50 to $300 million should.  It is important to realize that, soon enough, more PRVs will hit the market and suddenly lots of people, possibly your CEO or shareholders will be talking about them. The Cato Research advice is that you bone up on the PRV now and stay one step ahead of the regulatory curve.

Taken from FDA, “Priority Review means that the time it takes FDA to review a new drug application is reduced.  The goal for completing a Priority Review is six months.”  This is in comparison to a normal review, which aims for 12 months but is subject to review creep and often takes in the range of 14 months.  Normally Priority Review is reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists.  If a drug does not meet those criteria there is one other way for a drug sponsor to obtain Priority Review.

The Priority Review Voucher (PRV) is defined as a voucher issued by the Secretary that entitles the holder to priority review of any 505(b)(1) drug or 351(a) biologic.  In short, upon marketing approval of a drug that meets certain criteria, FDA will grant you a transferrable voucher that will give the bearer priority review of a drug of their choosing.  Currently the development of some drugs to treat neglected tropical diseases (NTD) or rare pediatric diseases (RPD) can qualify for issuance of a PRV.

The History

In 2006, three researcher at Duke University published a paper in the journal Health Affairs entitled “Developing Drugs for Developing Countries”.  Among other statistics in the paper they noted that despite the over one billion individuals affected by NTDs, that between the years of 1975-1999 only 1-2% of all new chemical entities were developed and marketed to treat those diseases.  What the authors proposed was to incentivize big pharma to develop drugs in the NTD arena.  To do so they suggested that the agency grant a voucher for priority review to a company who develops a drug that will treat a neglected tropical disease.  Furthermore they suggested that the original drug developer can use the voucher or that they can sell it on the open market, potentially to the developer of a blockbuster drug, where the shortened review would translate into extended patent life and considerable more value to the developer.

Backed by Sam Brownback (R-KS) and Sherrod Brown (D-OH) the original PRV for neglected tropical diseases was written into the Food and Drug Administration Amendments Act (FDAAA), and  in 2007 George W. Bush signed the legislation into law creating a new section, §524 to the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360n).  In October of 2008 the FDA issued draft guidance for Tropical Disease Priority Review Vouchers.  The guidance is provides an overview of §524 and helped to establish policies and procedures for execution of the program.

The Record

Skeptics both inside the FDA and in industry have taken shots at the PRV and have valid reasons to support their assertions that the program is a failure.  In a 2008 NEJM perspective subtitled “The Trouble with FDA Review Vouchers” author Aaron Kesselheim takes aim at the PRV.  Dr. Kesselheim insists, among other criticisms, that PRVs represent “an inefficient and potentially dangerous way of encouraging research into tropical diseases”.  The charges were rebutted in a 2009 NEJM letter to the editor by the original PRV authors, but the damage had been done.  The NEJM has given voice to detractors of the controversial program and a flurry of criticism followed.

While opinions vary concerning the potential for PRV’s to incentivize drug development, the track record of PRV’s, thus far, has left much to be desired.  So far only one PRV has been awarded.  It was issued with the approval of Novartis’ anti-malarial drug Coartem in 2009.  A test case for the value of the PRV on the open market has yet to be seen. Novartis did not sell the PRV,  instead they kept the voucher in house and redeemed it for the review of Ilaris, a drug they were developing for gouty arthritis.  The Agency determined that Ilaris was not approvable for the indication Novartis was seeking.  The review was completed in 6 months.

There were vocal critics for the issuance of a PRV for Coartem in the first place.  The argument followed that the spirit of the program was to spur development of novel drugs for NTDs, and that in the case of Coartem, which was already approved in 85 countries, the FDA had missed the mark in granting a voucher.  On the flipside others point to the fact that, since only one PRV has been issued since the inception of the PRV program that, in it of itself, points to a failure of the program.  Despite the criticism however the NTD PRV program continues and in 2012 a new PRV initiative was signed into law.  The Rare Pediatric Disease PRV program was designed as an improvement to the existing program and is the topic of the second half of this Ask CATO series.

This is a post by Matt Medlin, Ph.D.  Matt is a Regulatory Scientist at Cato Research and an Analyst for Cato BioVentures.