Orphan Disease R & D Has a Home at FDA

John J. Whyte, MD, MPH; Gayatri R. Rao, MD, JD


November 08, 2016

Editorial Collaboration

Medscape &

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The Focus on Orphan Diseases at FDA

John J. Whyte, MD, MPH: Hello. I'm Dr John Whyte, the director of Professional Affairs and Stakeholder Engagement at the US Food and Drug Administration (FDA). I'm here at the National Organization for Rare Disorders (NORD) Orphan Disease Summit with my colleague, Dr Gayatri Rao, who is the director of the Office of Orphan Products Development at the FDA. Thanks for joining me, Dr Rao.

Gayatri R. Rao, MD, JD: Thank you.

Dr Whyte: Tell us a little bit about what your office does.

Dr Rao: We are a small office that is tucked away in the commissioner's office, and we have a pretty remarkable mission. Our mission is to promote the development of products—all kinds of products, such as drugs, devices, biologics, and even medical foods—for patients with rare diseases. We do that in a number of different ways, whether it is through providing financial incentives, through our drug designation program, or through providing research grants to promote the development of important products for the patients who really need it.

Dr Whyte: You mentioned the grants program. Can you talk a little bit about how the grants program functions and how you might apply for it?

Dr Rao: Sure. It's interesting, because folks usually don't think about the FDA as an agency that funds research. When you think about funding, you think about the National Institutes of Health (NIH). However, the FDA has long had a grants program to stimulate the clinical development of products for rare diseases. Over the course of 30 years, we've spent more than $370 million funding clinical studies, and we have funded close to 600 studies in that course of time.

What's neat about this program is that it's really focused on funding those studies that really show promise in getting products out on the market. We're very proud of the fact that the studies that we've funded have gone on to contribute to approvals of more than 55 different products. In terms of who can apply, pretty much anybody can apply, whether you are domestic or international, whether you're a patient organization, academic, or industry. Almost anyone can apply.

In addition to that program, we launched a new grant program this year to fund the development of natural histories for rare diseases. It's a tiny program, a $2 million program, and we're hoping to fund about two to five different studies. It's to try to better understand the clinical course of these studies so that we can really inform how we design trials, what the right endpoints are, and whether we're studying the right population or not. This is the foundational stuff that is often missing in rare diseases. We're hoping that with investing in this foundational science, we'll really be investing in long-term product development.

Dr Whyte: Can you talk a little bit about which grants you were most proud of during the past decade or so?

Dr Rao: That's a long list. Today we are just announcing our newest grant recipients on our clinical trials side, and as a part of that initiative, we are funding 21 new studies for $23 million over the course of 4 years. As part of the 21 studies, we are funding several in the oncology space, specifically in pediatric oncology, which I'm very excited about. We're also doing a lot in pediatric rare diseases as well as funding a device trial. So there's a range of different product areas and diseases that we're targeting that I've been pretty excited about.

Involving the Patient Community

Dr Whyte: As I mentioned, we're here at the NORD Orphan Disease Summit, and we just listened to our commissioner, Dr Califf, talk about some of the issues around rare diseases. One of the topics he talked about is patient engagement.

Dr Rao: Yes.

Dr Whyte: How do we get the patient community more involved in our decision-making? You talk a lot about enrollment in clinical trials, so how do we do that? How do we get patients more involved, or how do patients themselves approach us? We often talk about the FDA as a big place, and it can be very confusing where to go.

Dr Rao: Especially in rare diseases, patients play a critical role in product development. I say "product development" because the focus is often on drugs, but we're talking about drugs, biologics, and diagnostics. Patients play such a critical role. The traditional roles that they've played have been in funding research and supporting one another. Those continue to be very important roles that they play, but they're increasingly becoming partners in drug and device development.

The first thing that's important for the patient community to do, particularly if they want to be successful in this area, is to really understand how the agency works. What is it that we actually need to do in order to make the decisions that we have to make? If patients really understand what that process is, that's the best way that they can educate their constituency, work well with industry, and provide meaningful input, whether it's in the design of clinical trials, what the endpoints should be, or what matters most to them. All along the spectrum of drug development, patients can provide input. The first step, from what I've seen, is understanding what we need in order to approve a product.

Dr Whyte: Many people are not aware that there have been a fair number of new drugs to treat rare diseases that were approved in the past few years. Could you talk a little bit about the state of drug development in rare diseases and whether you're hopeful for the future in terms of this space?

Dr Rao: It's a very exciting time for rare diseases. For a long time, there just wasn't as much focus on its development. In fact, I don't think my office would have even existed had there been a real market. But over the course of time, this has become an area of great interest, and that is in large part due to the success and the strength of the patient community in getting industry groups and academic groups interested in this space. Interest is growing, and we're seeing that many of the product approvals, when you look at percentages, are for rare diseases.

I'm always asked, "Look into your crystal ball. What do you see?" It's difficult to anticipate. Certainly, from my office's standpoint, we are seeing tremendous increases in the number of companies coming in to seek orphan drug designation. That's your gateway, essentially, to getting the incentives to develop your product. Year after year, the numbers have been breaking records. Do I think this is going to continue? I don't know. My sincere hope is that the interest in rare diseases is sustained. Even though there is this tremendous growth, if we take a step back and think about the larger context, there are more than 7000 rare diseases, and that number is likely much higher. When you think about that larger context versus the number of products that are actually approved to treat those rare diseases, it's a small fraction. There is still a tremendous unmet need out there. I'm hopeful that this interest will continue and will be sustained in the long run. I'm very excited and proud to be a part of that.

A World of Zebras

Dr Whyte: How did you get involved in rare diseases? Most of us as medical students and young physicians would not necessarily think that we're going to be involved in the disease that doesn't impact a lot of people. Tell us a little bit about how you got involved in rare diseases.

Dr Rao: I think that like many folks, one thing just led to another. I remember being in medical school learning about rare diseases and being told, "But those are the zebras. When a patient comes to you, don't look for the zebra; look for the horses." I never really thought that I would end up where my entire world is zebras and nothing but zebras. I was always interested in being in a place where what I did had the possibility of helping a lot of people. It may sound idealistic, but I've had the good fortune of being given the opportunity to work in an office where I get to do just that. Every day, we provide important incentives to companies. We interact with patients and researchers, all of whom are driven by the same mission. We want to develop products for some of the most vulnerable patients in the country, and I have the privilege of working in an office where I get to do that every day. I'm blessed.

Dr Whyte: How can people find out about your office?

Dr Rao: It's very easy to navigate the FDA website. The best way to find out about our office is to go to That will take you directly to our page, and we try our best to link you to other places within the agency that have important information. For folks who are watching, we try very hard to be accessible, so you'll see some contact names and numbers and emails. Please write or call. We do our very best to get back to you, so please write or call if you have questions.

Dr Whyte: Thank you, Dr Rao, for taking the time during the summit to share your thoughts about what your office does, as well as where you see the future of rare diseases.

Dr Rao: Thank you very much.

Gayatri R. Rao, MD, JD, is director of the Office of Orphan Products Development (OOPD) at FDA. The Office's mission is to advance the development of promising drugs, biologics, devices, and medical foods for rare diseases. As director, she oversees a number of programs created to promote the development of rare disease products, including multiple designation programs like orphan drug, rare pediatric disease, and humanitarian use device, as well as several multi-million-dollar grant programs. In addition, she serves as FDA's lead in coordinating cross-agency efforts on rare disease issues, is actively engaged in a number of internal and external collaborations, and oversees the OOPD's extensive outreach efforts to patients, sponsors, and other stakeholders.