Print BCTV: Therapies for Kids -- FDA, patient-focused drug development program for pediatric rare disease

Therapies for Kids

Transcript of BioCentury This Week TV Episode 172




Dr. Anne Pariser, Associate Director, Rare Diseases, FDA

Nancy Goodman, Founder, Kids v. Cancer

Art Estopinan, Chief of Staff to Rep. Lleana Ros-Lehtinen, (R-Fla)

Stephanie Bozarth, Vice President, National MPS Society Parent Advocate




Abbey S. Meyers,former president, National Organization for Rare Disorders


Dr. Richard Pazdur, Director, Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, FDA

European Medicines Agency

Creating Hope Act

Pediatric Rare Disease Priority Review Voucher program



Steve Usdin, Senior Editor




STEVE USDIN: This week -- what can be done to get new therapies to kids with rare diseases? We'll ask FDA and parent advocates. I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Your trusted source for biotechnology information and analysis. BioCentury This Week.


STEVE USDIN: Can government do more to help children with rare diseases? FDA is holding a meeting this week to get ideas and will release a congressionally mandated plan later this year. Researchers and parents will press the agency to make it easier and more attractive for companies to create new drugs for rare pediatric diseases. This week, we'll meet three parents who have faced terrible diseases in their own families and been transformed into patient advocates. After Nancy Goodman lost a son to brain cancer, she started Kids v. Cancer and persuaded Congress to enact the Creating Hope Act, a law that creates new incentives to develop drugs for rare pediatric diseases.


Art Estopinan's son Arturo was born with a rare and usually fatal disease. His family has not only fought for Arturo's life, but also to increase awareness of rare diseases. Art received the Rare Voice Public Service Award from Rare Disease Legislative Advocates for his efforts on Capitol Hill, where he serves as Chief of Staff to Representative Ileana Ros-Lehtinen of Florida. Stephanie Bozarth's daughter has MPS-IV, also called Morquio Syndrome. In addition to caring for Annabelle, Stephanie serves on the Board of Directors of the National MPS Society and chairs its committee on federal legislation.


I'm pleased to be joined by Dr. Anne Pariser, FDA associate director for rare diseases. Dr. Pariser, about a third of the new drugs that were approved over the last decade were for orphan conditions, for very rare conditions, which sounds like a lot, except that when you get down to it, that's about 10 drugs a year. And there are about 7,000 rare conditions. Is there anything that FDA can do or is doing to try to accelerate the development of drugs for rare diseases to get more new drugs out to patients who need them?


ANNE PARISER: Yes. That's a really good question. You're right, there's about 7,000 rare diseases. Most of them don't have approved treatments, and most of them are serious. So there's a very high unmet medical need. Rare diseases is a high strategic priority for FDA, and we have a number of programs -- some of them are new, some of them are longstanding -- that we've been using to try to accelerate rare disease drug development and approvals.


STEVE USDIN: There's a particular thing called accelerated approval, which is approving drugs based on a surrogate endpoint -- something other than a hard clinical endpoint. And there's a lot of controversy about that in the rare disease community, and a feeling that FDA hasn't done enough to make that mechanism available for rare diseases. A couple dozen members of Congress have signed a letter asking FDA to do more to make accelerated approval available for rare diseases. Is that something you're considering? Is it something that's feasible?


ANNE PARISER: It's something that we've been working on for a long time, and something we've been quite interested in. It's a way to incorporate flexibility into rare disease drug development and drug development for serious illnesses, as well. Most accelerated approvals for new drugs are actually for rare diseases. For the past 10 years or so, it's mostly been for rare cancers, but there have been some other rare diseases in there, as well. But as you noted, the difference between accelerated approval and a traditional approval is usually based on the endpoint, and most rare disease approvals are actually based on surrogates or biomarkers -- usually some kind of a lab test. And a lot of those do receive traditional approvals.


STEVE USDIN: So most of those are either for cancer or they're endpoints that are traditional -- ones that have been known about in medicine for a long, long time. Is there is there a way to get over the hump, to be able to use accelerated approval to create new endpoints for accelerated approval for rare diseases, do you think?


ANNE PARISER: Certainly an area of intense interest and something that we're always trying to work towards. A lot of this goes towards the understanding of the disease -- the mechanistic basis, how the drug impacts on that, and then very importantly, how does that drug impact on patients? Because the ultimate goal is you want to know that the treatment is benefiting patients.


STEVE USDIN: So let's talk about patients. One of the things that FDA's talked about a lot and we've talked a lot about on this show is the idea of patient engagement with drug development, with drug regulation. Has it gone beyond just talking about it? Are there any examples in rare diseases that you can discuss where patient engagement has actually changed the way that FDA thinks about things?


ANNE PARISER: I think there's a very long tradition of that, and for rare diseases, the patients have often usually been the driving force behind a lot of the research. This goes back quite a ways to the Orphan Drug Act, which was actually the work, largely, of a mother with two sons.


STEVE USDIN: Abbey Meyers, yes.


ANNE PARISER: Yes, Abbey Meyers. And then, obviously that's really accelerated orphan drug development, but there's been many other ways. Some more recent examples -- I'm sure you've heard of the Patient-Focused Drug Development Program. We're trying to get the community in to talk about how the diseases impact their life and to hear about the things that are important to patients with the hope that then this helps inform clinical trial design and endpoints.


The first rare disease patient-focused drug development meeting for narcolepsy was held about a month ago, and it was very successful. There was a good turnout in the community. There was a lot of discussion. There was a lot of good information. A lot of our staff went, and they did note that it was very informative. So we're looking now -- how do you spread this to more diseases other than the ones just at the meeting? And there's a number of ways. We're looking into that.


STEVE USDIN: In the early AIDS experience, AIDS activists were involved not only just in having meetings like that, but they were actually sitting down at the table and helping to design protocols and helping to define the risk-benefit -- sitting down with FDA reviewers. Is that a model you think we could go back to for rare diseases?


ANNE PARISER: Yes, and actually, it's ongoing. That's a patient representative program, so patients can become special government employees and take part in review, often at the point of the marketing application, and sit in on advisory committee meetings. And we have done that for a number of rare diseases. Cancer does that frequently, but also some of the genetic disorders. For example, the program I worked on a few years ago for Pompeii disease, we did have a patient representative and she took part in the meetings and the advisory committee. And her advice and her perspective was actually very valuable to the review team, so that is something that is done.


STEVE USDIN: Dr. Pariser, you've got a meeting coming up, a three-day meeting about rare diseases. What's on the agenda there? What are you hoping to accomplish?


ANNE PARISER: We're looking to hear from the broad rare disease community. Rare disease is usually described as a team sport, so we need industry and academia and patient advocates and government as well to come together, and we want to hear the diverse opinions of the community. And then we're going to take that information, and it's going to help inform first a report and a summary of the meeting and then also for the pediatric part, it will help inform a strategic plan, looking for priorities moving forward, how to best use resources, and how to coordinate.


STEVE USDIN: Next, we'll hear from three parent advocates. First, here's Representative Ileana Ros-Lehtinen on the floor of the Congress about pediatric rare diseases.


ILEANA ROS-LEHTINEN: I first heard about mitochondrial diseases, which are fatal, from my Chief of Staff Arthur Estopinan who, together with his lovely wife Olgita have been caring for their baby after he was diagnosed with TK2, mitochondrial DNA depletion syndrome.




STEVE USDIN: I'm pleased to be joined by Nancy Goodman, founder of Kids v. Cancer; Stephanie Bozarth, a member of the board of the MPS Society; and Art Estopinan, father of a child with a rare disease and a prominent Hill staffer. I'm going to ask all of you -- nobody signs up to be a parent of a child with a rare disease and become an advocate. Life kind of throws it at you. I'm going to ask all three of you to kind of talk about your journey -- how did you get into this, your experiences with your children -- start with Art.


ART ESTOPINAN: Yes. Well, thank you. Thank you so much for having us here today. And that is the case. About a year and a half ago or so, we noticed that our baby was showing signs of weakness. And all of a sudden, he was getting worse and worse.


And then my wife and I became proactive contacting the doctors, and even having strong discussions with our pediatrician that there was something wrong with our baby. And so it progressed in that direction. And now I have been working in trying to get our son the proper attention, and medical attention, that he needs for his very rare and very aggressive muscular disorder.


STEVE USDIN: Mm-hm. Stephanie.


STEPHANIE BOZARTH: My daughter, Annabelle, is seven years old now. But about four months old, I noticed some differences in her spine. And when I was actually burping her, I noticed that. Quickly, I told the pediatrician about it. Within two months, we did narrow it down to mucopolysaccharidosis, type four.


There's 11 different types. They affect the body in similar ways, but they all have their own little differences. So early on -- we've known since she was six months old what she had. And we joined the National MPS society. We started fundraising immediately.


We delve into the world of figuring out what we needed to do for her medically. One of the things that it does cause is a lot of spinal instability along with a lot of bone changes. So she, at seven years old, has already had over seven major surgeries, which were lifesaving in some cases, and also have kept her out of a wheelchair because of the bone changes in her body.


Since joining the national MPS society, I then decided to join the board of directors. I'm very passionate about trying to get us to treatments, and hopefully one day, cures. And I'm part of running the legislative committee for the MPS society, and keeping us educated -- the whole society, which is over 700 members, on what's important, what we need to know about to move that ball forward for all of our kids.




NANCY GOODMAN: Well, my son Jacob was a normal, healthy child for 8 and 1/2 years. And then one day, he started having headaches and dizziness in the morning, but he was fine in the afternoon. It took us two months to get a diagnosis of medulloblastoma, which is a rare form of pediatric cancer. Jacob was diagnosed on a Monday afternoon at 3:00. He had surgery Tuesday morning. And he was never the same again.


He suffered traumatic brain injury, although the surgery did save his life. And then he went on to two years of chemotherapy, radiation. But the treatments were not effective, and Jacob died two years later. And before Jacob was diagnosed, I knew nothing about pediatric cancer. I assumed that kids were cured. And I assumed that because there's this incredible industry for oncology in the United States that kids are really OK when they have cancer.


And it turns out that there's almost no drug development for pediatric cancers. Even though we have a pipeline of 900 drugs for adult cancers, it's close to zero for pediatric cancers. And so Jacob died and I started Kids v. Cancer.


STEVE USDIN: So briefly now, and we'll pick it up a little more, I want to get kind of your responses to what Dr. Pariser said. What do you hope for? What do you expect could happen from the FDA, from regulators, to advance the development of drugs for kids with rare diseases?


NANCY GOODMAN: So I think the first thing we just need to talk about as a society is the fact that we have this incredibly robust pharmaceutical industry, but it is really designed to hit the major diseases -- the major adult cancers, heart disease -- and seriously ill kids have rare diseases, and they are largely neglected by the pharmaceutical industry. So what can the FDA do about it?


STEVE USDIN: Let's talk about that -- I'm sorry, we have to take a break. Let's talk about that when we come right back.




STEVE USDIN: We're talking with three parent advocates about creating new therapies for rare pediatric diseases. Nancy, I want to pick up where we left off there when you were saying about FDA creating new incentives for companies to develop drugs for rare diseases.


NANCY GOODMAN: Right. Well, first of all, I do want to say that Rick Pazdur, who's the director of the Oncology Division at CDER, has done a great job by kids with cancer, and he has pushed innovative trial designs harder than industry.


And so we hope to continue to work with him to find ways to get access to drugs for kids on compassionate use, single INDs if necessary but, more importantly, for pre-clinical study and for pediatric trials. And we know Dr. Pazdur and the FDA is on board, and we hope that we can work with industry.


STEVE USDIN: Yeah. And Stephanie, kind of what's your response? What are your issues with regulators for patients with kids with MPS?


STEPHANIE BOZARTH: For kids with MPS -- it's a progressive disease, and the average age is around 14 for children with MPS. Some of the things that are important to us at the MPS Society is looking at how many of our trials, early-phase trials, are going over to the UK and Europe. They're starting the Phase I, Phase II trials there. And a lot of that is based on how the flexibility of the international harmonization laws, guidelines, are applied here at the FDA.


We are hoping to have some more flexibility applied when we're looking at giving a child back a known biologic into the body, that there's a low probability of toxicity. This would apply for many kids with lysosomal storage diseases that are missing an enzyme, and we're looking to replace that enzyme, which is exactly what my daughter's been going through in a clinical trial right now.


STEVE USDIN: And the idea there, part of the idea there, is that for kids with rare diseases, or anyone with a rare disease, trials are not just about studying a potential treatment. They're really a form of early access for these patients. And a large percentage of the patients with a rare disease might be on a trial.


STEPHANIE BOZARTH: Absolutely. We were following very closely where this research was going for our daughter's own clinical trial. And immediately, as it was announced, it was, how do we get our daughter into that trial? She needs the medicine now. Every day that she is on a treatment, it's a day that we're possibly slowing that disease progression down, so it is critical.


And when you start a clinical trial at the Phase 1, Phase 2 over in Europe and the UK, that is a minimum of at least two years. That it's two years of -- a lot of kids don't have that much time. So it's important that we figure out a way that we can start early phase clinical trials here so children can have access to these treatments earlier and slow the disease progression.


NANCY GOODMAN: If I could jump in here too, Stephanie, and I really agree with you. For rare diseases, the regulatory process is very expensive for companies to undergo. And why not create a regime in which the FDA recognizes the EMA's approval of a drug for rare disease, and similarly, the EMA recognizes the FDA's approval for a drug? That way, we won't have situations in which there are drugs available for kids with rare diseases in Europe, but not the United States.


STEVE USDIN: Do do you think something like that probably would require legislation? Art, what's the receptivity on the Hill to legislating in this area of rare pediatric diseases?


ART ESTOPINAN: Well, I think I would like to share the same story with my son. The clinical trial started in Europe, in Spain and in Italy, and my son is the only American baby that is undergoing the treatment.


I think that there is a willingness to look into this. I think most members of Congress run to help their community, and helping babies and other children that are very sick and need pediatric immediate attention and medicines to keep them alive is something that I have found that people, our members, are very receptive.


And in my son's case, if it wasn't for his medicine, he wouldn't have survived but one or two more months. His disease is very aggressive, and it was very progressive. And these clinical compounds are critical not only in sustaining him alive, but in making him stronger.


STEVE USDIN: What's the role of NIH? What's the role of government? And should it be playing a bigger role in developing drugs for these ultra-rare diseases?


NANCY GOODMAN: That's right. Major diseases, like breast cancer or heart disease, have a lot of investment by private industry. Whereas, the rare diseases, like the diseases that Annabelle and AJ, Jr., or Jacob, had, are not really addressed by private industry just because they're so rare. The markets are small. So maybe we need to double down, and we have to have a discussion, as a society, about whether that should be one of NIH's roles.


STEPHANIE BOZARTH: And rare diseases, actually there's just over 7,000 that we know of, only a very small percentage of those have any treatments or cures. So about 95% of those do not have any treatments or cures, and the vast majority of those are pediatric. Those are kids that are getting sick and not surviving. So I think it is important that we let . . .


STEVE USDIN: So Art, do you think that there would be receptivity in Congress to more aggressively kind of instructing NIH or orienting it toward these rare diseases and being that kind of prescriptive?


ART ESTOPINAN: I believe that the conversation needs to happen. And I believe that we need to, with the science developing medicines so quickly and advancing so rapidly, we need to start this conversation now.


Always when there is a niche, when there is a bureaucracy, when there is an established organization, when you try to shake things up, you're going to have resistance. But that doesn't mean that we should not start because the lives of many babies and kids depend on having an aggressive program to help these kids with very rare diseases.


Like I said, if it wasn't for the Compassion Bill that the hospital was able to start providing the experimental meds for my son, he wouldn't be with us today. And he's been home now for several weeks, and we, God willing, will continue to pray for him to stay at home after being 13 months in the hospital.


The doctors didn't tell us that this was possible. They told us go home. He will die in two months. This was last July of 2012. But we kept on fighting, and he's a fighter. And science is moving really fast.


STEVE USDIN: We're going to come back. And what I want to do is maybe ask each one of the three of you for some final thoughts and maybe what you'd like to see Congress doing to advance therapies for rare pediatric diseases.


SPEAKER: Now in its 21st year, visit for the most in-depth biotech news and analysis. And visit for exclusive, free content.




STEVE USDIN: We're going to finish up this show today talking about legislation on pediatric rare disorders. Art, you were talking there about your experiences in Congress. And I know that you're advocating not just for your own job, but more broadly. What is it that you'd like to see Congress do?


ART ESTOPINAN: I think that as science continues to improve at lightning speed, and innovation is keeping more and more babies that would have passed away alive now, I think that it would be good and very productive for Congress to work and continue to develop different programs and legislation that is able to help these children.


STEVE USDIN: That's targeted specifically in pediatric diseases.




STEVE USDIN: Stephanie.


STEPHANIE BOZARTH: I think it's important that we look for incentives to continue the ball rolling with research in rare diseases and pediatrics also. Understanding the investment in NIH is critical. It's building jobs. It's actually, more importantly, for us saving lives. So that's where we focus on.




NANCY GOODMAN: You know, I have a good story to report with respect to Congress. And that is that, in 2012, as part of the FDA's Safety and Innovation Act, Congress did pass the Creating Hope Act as the Pediatric Rare Disease Priority Review Voucher program. And this creates a market incentive for pediatric rare disease drug development in the form of a priority review voucher.


So we're waiting for the FDA to publish the designation form and the draft guidance. But as Dr. Pariser mentioned, there's already been quite a bit of interest in this program.


ART ESTOPINAN: And reaching your member of Congress is a process of an education. We have to educate them in these complex rare diseases, and I believe that with that education, it will empower them to move forward.


STEVE USDIN: And you mentioned incentives. Do you think that there's a scope, and that there's a need for other kinds of incentives to make it more economically feasible for companies to invest in these very, very rare diseases?


NANCY GOODMAN: Absolutely. The Creating Hope Act is an important first step, but it's not going to solve the problem. The fact is it's very expensive to develop a drug. And how do you develop a drug for a child, like Art, Jr. who has a disease for which there are what? 100 kids in the United States who have this disease? 50? 10?


ART ESTOPINAN: No. He's the only one in the U.S. that is diagnosed that we are aware of. There's a young lady in New Jersey. But I mean, a there are only 40 in the world.


NANCY GOODMAN: I mean, why not save him? He's a little 2 and 1/2-year-old boy on a trach [sic] who's immobile. I mean, as a society, we should be helping our most vulnerable kids.


STEVE USDIN: And Stephanie, you mentioned NIH is part of it. I mean, it sounds like when we're dealing with diseases that are so rare that there are only a handful of kids around the world that have them, that's going to be something where the government's going to have to step in, isn't it?


STEPHANIE BOZARTH: Absolutely. We do need NIH to appropriate more fundings and grants towards rare diseases. That is where we actually get the big grants. I know there are many patient advocates. We raise money. We raise money for researchers to get the pipeline going with a lot of this research. But then it requires these larger, major grants like from the NIH that actually get it from the lab to the bedside. We have to have that support.


NANCY GOODMAN: And the question is, why do we have an NIH? Why not just have an extramural program that funds academic medical institutions? And what does the NIH do that's special? And maybe it's focusing on pediatric rare diseases or rare diseases generally that private industry has a really tough time developing drugs for.


STEVE USDIN: That's this week's show. I'd like to thank my guests Anne Pariser, Art Estopinan, Stephanie Bozarth, and Nancy Goodman. Have a thought about today's show? Remember, you can tweet it using the hashtag#BioCenturyTV. I'm Steve Usdin. I'll see you next week.