FDA's Rare Disease Program: A Rare Opportunity to Help Kids

Laura A. Stokowski, RN, MS,Anne Pariser, MD; Andrew Mulberg, MD


March 18, 2014

Editorial Collaboration

Medscape &

In This Article

Editor's note:
The US Food and Drug Administration (FDA) has just approved the first product under the new rare pediatric disease priority review voucher (PRV) program. Elosulfase alfa (Vimizim™) is a new type of enzyme replacement therapy (ERT) that received a PRV, which can now be awarded to the sponsors of new rare disease drug or biological products that meet certain criteria. The PRV program is administered through the FDA's Office of Orphan Products Development. Elosulfase alfa is now approved to treat mucopolysaccharidosis type IV A (MPS IVA), Morquio A syndrome, a rare, autosomal recessive lysosomal storage disease caused by a deficiency in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Medscape spoke with Anne Pariser, MD, Associate Director for Rare Diseases, Office of New Drugs, Rare Diseases Program, at the FDA's Center for Drug Evaluation and Research (CDER), and Andrew Mulberg, MD, Deputy Director, Division of Gastroenterology and Inborn Error Products (also at CDER), about the PRV program, the recent approval of elosulfase alfa, and the lessons for clinicians caring for children with a rare disease.

Orphan Drugs for Rare Pediatric Diseases

Medscape: Can you start by explaining what qualifies as a rare disease for the purposes of an orphan drug treatment in your program?

Dr. Anne Pariser

Dr. Pariser: In the United States, a "rare" or "orphan" disease is a disease that would meet the legal criterion of affecting fewer than 200,000 patients. Most of the time, however, we are talking about diseases that have a much lower prevalence than that. Most rare diseases affect 20,000 people or fewer, so we are primarily talking about small numbers of patients. Individually, these disorders affect small numbers of patients, but when you look at them collectively, it is estimated that 25-30 million Americans (about 1 in 10) have a rare disease, so it is a very large public health concern. Therefore, we care very much about patients with the individual diseases and also about the larger public health considerations that go along with the problem of rare diseases.

Most of these are serious disorders. Many of them affect children, and as you know, they occur across a spectrum of how rapidly they progress and their clinical manifestations. We don't have good prevalence estimates for most of these diseases. They are hard to diagnose. Patients often describe going years without a diagnosis, and having to go from doctor to doctor and from center to center trying to get a diagnosis. The more severely affected patients with the more rapidly progressive disease courses are the patients who tend to come to medical attention, but there are other patients who are at the more attenuated, slowly progressive end of the spectrum who may not come to medical attention and are only diagnosed after a family member has been identified.

Medscape: Elosulfase alfa was the first orphan drug to come out of the rare pediatric disease PRV program. Could you explain how the new program differs from the previous voucher program for neglected tropical diseases (NTD) and how you anticipate that this program will enhance the development of treatments for rare pediatric diseases?

Dr. Pariser: The pediatric rare disease PRV program was modeled after the NTD voucher program, which is still up and running and is still available. The main intent of that program was to provide an additional incentive for drug sponsors to pursue these drugs. What both of them have in common is that if you have a new product that qualifies -- in this case for a rare pediatric disease -- and the marketing application is submitted to the FDA, and it qualifies for a priority review, then if that drug is approved, at the time of approval a voucher will be given to the drug sponsor. They can take that voucher and apply it to a different drug in the future to convert that marketing application review from a standard review to a priority review. The main difference between a priority review and a standard reviews is that the FDA's review clock is 4 months shorter for a priority review.

Another benefit is that the drug company doesn't have to use that drug voucher themselves. They can sell it to someone else, and that can be a financial incentive. That is the very basic outline of the voucher program. What does the pediatric voucher program have that is different from the NTD voucher program? The pediatric voucher can be transferred any number of times. There is no limit to how many times the voucher can be sold and resold and resold again, which we hope will make it more valuable and more flexible. The NTD voucher can only be transferred once. The sponsors also have to notify the FDA when they want to redeem the voucher; for the pediatric voucher, it's 90 days in advance of the marketing application, whereas for the NTD voucher, it was a year. This was an attempt to provide more flexibility and increase the voucher's value.

What the pediatric voucher also offers is the opportunity to designate the product during the development time, during the investigational new drug phase. It can be designated as a rare pediatric disease if the sponsor chooses. They can do this if they want to. It's not required to have a designation if the sponsor wants to request a voucher later on, but that is also something that was thought to increase the attractiveness of the program -- the company could show the investment community, for example, that they qualified as a rare pediatric disease on the marketing application. These were the 3 major points that were tweaked with the existing NTD voucher program to make this more attractive.