Print﻿ BCTV: Seeing 20/20 - Global project to create 200 rare disease drugs by 2020

Seeing 20/20

Transcript of BioCentury This Week TV Episode 149




Ruxandra Draghia-Akli, Director, Health Research, European Commission

Lu Wang, Program Director, National Human Genome Research Institute

John Walsh, President and CEO Alpha-1 Foundation

Rogerio Vivaldi, Senior Vice President and Head of Rare Diseases, Genzyme




Orphan Drug Act

Nager Syndrome

Gaucher Disease

Viking Disease

International Rare Disease Consortium

Mendelian Centers




Human Genome Project




Steve Usdin, Senior Editor




STEVE USDIN: This week, a patient, a scientist, a physician, and Europe's top science funder discuss tackling rare diseases. I'm Steve Usdin. Welcome to BioCentury This Week.




STEVE USDIN: Few areas of medicine have seen as much progress over the last 20 years as the creation of new therapies for rare diseases. Despite the successes, the unmet need is enormous. There are treatments for only about 200 of the estimated 7,000 to 8,000 rare diseases. Ironically, there's so many rare diseases that having a rare disease is relatively common. About 60 million people in the U.S. and Europe have a rare disease.


Patient advocates persuaded Congress to pass the Orphan Drug Act in 1983. The law gives drug companies the right to sell products for rare disease, defined as a condition affecting 200,000 or fewer Americans, for seven years without competition. Scientific advances, particularly the plummeting cost of gene sequencing, have cut the cost of diagnosing and researching rare disorders.


This week, we'll hear from the European Commission's Ruxandra Draghia and NIH's Lu Wang about an ambitious, international project that hopes to develop therapies for 200 rare diseases by 2020. We'll discuss the need to create better policies to ensure access to rare disease therapies, with a Genzyme executive, Rogerio Vivaldi. And we'll hear how a high tech therapy is transforming lives in the Amazon rainforest.


First, a patient advocate, John Walsh, describes how an organization he started - the Alpha-1 Foundation -- has found an innovative way to fund investments and research on a once fatal rare disease. I'm joined now by John Walsh, Co-founder, President and CEO of the Alpha-1 Foundation. John, what led you to start the Alpha-1 Foundation? What was the experience that led you to start it?


JOHN WALSH: We participated in a seven-year longitudinal disease progression study that was a Phase Four requirement for the first orphan drug approved for Alpha-1. When that study was completed, the NIH advised us they were not going to do any more research intramurally or extramurally on Alpha-1. That was obviously unacceptable to us as a community. So we started the Alpha-1 Foundation to provide the leadership and resources to increase research, improve, help, promote worldwide detection, and ultimately cure Alpha-1.


STEVE USDIN: And what's been your experience? What have you accomplished since starting the Foundation? And also to back up, when was it started?


JOHN WALSH: We started the Foundation in 1995, focused the first three years on building the infrastructure to support the international investigator community. So we have the largest registry in the world of Alpha-1, largest DNA and tissue bank, and translational research lab and genetic lab, which is all really served to really be able to recruit for clinical studies very rapidly. And the registry itself allows us to recruit for a Phase 3 pivotal study within six to eight weeks.


STEVE USDIN: So one of the issues -- so you're working on two fronts. One front is trying to develop new and better therapies, but also to get people access to the therapies that they have now. About the access issues -- how much does it cost in the United States? And how many percent -- what percentage do you think of people who are diagnosed with it get access to the therapy?


JOHN WALSH: So in the US, we had our reimbursement battles right out of the gate when it was licensed. The therapy now costs somewhere between $130,000 and $150,000 per year per patient. We've really focused on making certain that we maintain reimbursement. And we have a medical director that discusses the medical necessity needs with payers and in the U.S., pretty much anybody that qualifies for augmentation therapy gets access to it.


STEVE USDIN: And that's a weekly infusion, right? They have to go into it, out-patient setting, or do it at home once a week?


JOHN WALSH: We do it weekly. About a third have to go into clinics to do it, because of Medicare regulations. But some of us self-infuse. But most people have a nurse that comes to infuse them in their home or work.


STEVE USDIN: So there's a high incidence of this disease in Europe. You told me it's sometimes called the Viking disease, because there's kind of a legacy of it coming from northern Europe and spreading around the world. What's access like in Europe?


JOHN WALSH: Access is tough in Europe. In Norway and Sweden, it's about 1 in 1,600 individuals that are homozygote for Alpha-1, U.S., we're 1 in 2,750. We just came back from an international patient Congress, our fourth in Barcelona, Spain. And we had a workshop on access and how to create a toolkit to assist individuals with Alpha-1 to be able go and advocate, country-by-country, with their health care system and their payers for access to therapy.


STEVE USDIN: And what are the statistics like now? Patients who have the condition in different countries in Europe, do you have any idea how many people are covered? How many people know that they have the disease and can't get covered?


JOHN WALSH: Unfortunately, there's only three countries, and in one case, Belgium stopped covering anybody after a certain date last year, so there are four countries in Europe that you can have access to augmentation therapy.


STEVE USDIN: And what are the consequences of not having access to it?


JOHN WALSH: There's no question that a lot of us on augmentation therapy wouldn't be alive today without it. It slows the progression of the disease down. It improves our quality of life. The reality is if you don't have access to augmentation therapy, you're going to get more frequent infections, hospitalizations, pneumonias. It's going to be more rapidly progressive. And you have a decline in lung function.


STEVE USDIN: So you're working on that front of trying to improve access. Very quickly, what are the things you're trying to do also to develop better therapies


JOHN WALSH: So we've done we've actually funded $47 million of research at 96 institutions in North America, Europe and New Zealand and Australia. So we are really committed to support the international investigator community for the next generation of therapies, not only aerosolyzed therapy, which would give us a more direct and efficient dosing of our augmentation therapy. But also we are working on stem cells, gene therapy, small molecule therapies.


STEVE USDIN: Great. Well, thanks, John Walsh. Next, we'll speak with Genzyme's Rogerio Vivaldi.


NARRATOR: You're watching BioCentury This Week.




STEVE USDIN: One company, Genzyme, pioneered the development of orphan drugs. Today, I'm pleased to be joined by Rogerio Vivaldi, Senior Vice President and Head of Rare Diseases at Genzyme, part of the global pharma company, Sanofi.


Dr. Vivaldi, we just heard from John Walsh, who was a patient who was talking about the difficulties of getting access to a life extending therapy in wealthy countries in Europe. If we're going to be talking about creating 200 new therapies by 2020, don't we need to be talking about the access issues today?


DR. ROGERIO VIVALDI: Yeah, I think that the -- I always say that I'm extremely optimistic about the science, how can we really develop new therapies? How can we diagnose new diseases? But the access is something that we have to focus on. Because there's nothing worse than to be able to do something and not do. I describe this as the phenomena of a health care by zip code. And depending on where the patient is, may not have the access to that new therapy.


STEVE USDIN: It's not a zip code in the United States as much as it is around the whole world, right?


DR. ROGERIO VIVALDI: Yeah, I was fascinated when I moved to the U.S. to find that even in the U.S. you have this. Because I am from Brazil. And in Brazil, you have Sao Paulo, it is a large city, 22 million people in the northeast. In the northeast where you really have the poverty. So I saw the differences there.


But today, with the rare disease, became too visible. So everybody wants to discuss this. And of course, it's much more difficult for you to have really big evidenced data with a so small population. And then I am sure that we have to build a framework that guarantees that we have a good biology, we have a clear defined patient need, and then we have to have a process on how can we change that life and have a dialogue to how this could be sustainable and maintained by the society.


STEVE USDIN: So I mean, the obvious problem, and the issue that Genzyme dealt with in its way was the fact that it costs just as much to develop a drug for a very rare disease that only a few people have as it does for a disease that many, many people have. How are you going to deal with that in an era when every country in the world is trying to cut down on healthcare costs?


DR. ROGERIO VIVALDI: I think that this is all about being transformative. Today, you have many medicines that do not do their work. And in our case, we have transformative drugs, drugs that are very specific. You can say that they are personalized. But they are. And this guarantees the efficacy. And if it guarantees the efficacy, then you basically, you're not -- everything that you're doing works.


And this is the difference with the common medicines -- that a majority percent doesn't work. So for me, it is absolutely clear that there is a space. And again we're talking about 2% or 3% of any budget of any healthcare system for these drugs. We're not talking about the 97%. We're talking about the 2%, 3%, of the things that work, transform those patients, and not only the patients, the family.


If we imagine a child that has a very devastated disease, that creates a family problem. If you simply transform that disease, you'll be transforming the whole family. The value for the society with this transformation, we didn't put, really in paper still today. We must do. Because we must demonstrate that the value is beyond even the person. It has to go with family. It has to go with the whole society -- what we gain by treating that patient in that such very rare disease.


STEVE USDIN: So you're really talking about -- it is very interesting. So you're talking about looking at the value to the individual patients, looking at that value to their families, and then a wider value to society as a whole.


DR. ROGERIO VIVALDI: Yeah, a father who has a three-year-old child, he will stop to work, or he will change his work, in order to really to help his child.


STEVE USDIN: I find it really interesting and fascinating that Genzyme's really, really expensive and complicated therapies have been able to be applied and used in a country like Brazil, and even in less developed parts of Brazil. Can you talk a little bit about that, and about your experiences in really remote parts of Brazil?


DR. ROGERIO VIVALDI: So I had the privilege to be the treating physician of the first Gaucher patient in Brazil 21 years ago. So back in 1992, we start treating someone in Rio. But then we were just so really intense to promote education. And we were basically working with many hospitals, many doctors. We created a legion of doctors to go out through the country to find Gaucher patients. And as a result, we had one particular doctor that, in one of his visits to a tribe, in the Amazon region, he brought his poster with a big picture of a patient with Gaucher disease not on therapy.


STEVE USDIN: And they have a very distinctive look, right, because their liver and their spleen is enlarged and --


DR. ROGERIO VIVALDI: Yeah, Gaucher has this peculiarity in terms of, you see, clearly, what the patient has. So you can clearly see the thin bone. You can see the liver. In this case, this boy had a 100 times the normal size of his spleen, 15 times the normal --


STEVE USDIN: This was a boy whose mother, right, came into a doctor's office in a remote area in the Amazon?


DR. ROGERIO VIVALDI: So then, in the following visit a mother was there and said, look, I have a son that looks exactly like the picture. And the doctor said, bring him in, and we can test him immediately, because with the dry blood spot technology. So in the tribe, in the Amazon, in South America, in Brazil, he was able to diagnose in two days.


That patient was put on therapy. Later on, we found that he had another three cousins with the same disease. So we have now between three-to-five Indians receiving enzyme replacement therapy for Gaucher disease in Brazil.


STEVE USDIN: And how does that work physically, because they're not in a city, are they?


DR. ROGERIO VIVALDI: No, they are in the tribe, in the forest, in the Amazon forest, which is the largest forest in the world. So they received the drug, the doctor brings every two weeks. The treatment is every two weeks by infusion. And they do their infusion in the tribe where they are.


STEVE USDIN: And bringing it means that there's actually what, there's a boat that goes from Manaus, from a city in the middle of the Amazon?


DR. ROGERIO VIVALDI: There's a boat with a fridge. And you keep the vials of the medicine in the fridge. And then you provide this to the patients. And they're doing this for, now, I think between three to four years now. And they are doing fine. They had their life transformed, even in the forest.


STEVE USDIN: Next, the International Rare Diseases Consortium has set an ambitious goal to create therapies for 200 rare diseases and to create diagnostics for virtually all rare diseases by 2020.


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




NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: Finding new therapies for 200 rare diseases and diagnostics for virtually all rare diseases by 2020. That's the goal of the International Rare Disease Consortium. To discuss this ambitious effort, I sat down with Dr. Ruxandra Draghia from the European Commission and Dr. Lu Wang from NIH.


This goal of getting 200 new therapies by 2020 and of having diagnostics for virtually all rare diseases, why is that something you feel like you can accomplish now? What's different now from, say, 10 years ago?


DR. RUXANDRA DRAGHIA-AKLI: The idea of the International Rare Disease Consortium is collaboration. And I think that we are now in the midst of a better trust and understanding between the different types of investigators -- academic, small or medium enterprises, industry that have been catalyzed around these goals. So not only the scientific knowledge -- and I'm sure that Dr. Wang would address that -- but also the fact that we are in a very favorable collaborative time.


STEVE USDIN: So part of it, though, is the science, isn't it?


DR. LU WANG: Yes. So I would like to go back to the Human Genome Project, which initiated 10 years ago. After the completion of the Human Genome Project, a lot of important biomedical projects started. So, essentially the completion of the genome made revolutionary influence to biomedicine.


And for the diagnostic tools and treatments to be made, one needs to understand the genetic basis of these diseases to start with. With the knowledge of the human genome sequence and the methodologies in sequencing and data analysis that have been developed and continually been sharpened, it is now possible to make rapid discovery of the genetic changes underlying rare diseases at large scale in a rapid fashion.


STEVE USDIN: So you're talking about coming up with 200 therapies in this period of time, being able to diagnose most rare diseases. What's the total universe of rare diseases that you think that's out there? And what are some of the kind of milestones along the way between now and getting these new therapies.


DR. RUXANDRA DRAGHIA-AKLI: An estimated 6,000 to 8,000 rare diseases exist. We have approved therapies for about 200 of them. It is estimated that both in Europe and in the United States, if one puts together all the patients that are affected by rare diseases, we are talking about 30 to 35 million individuals each.


So while each disease might be rare, the number of patients that are affected is in fact, very substantial. To achieve the goals by 2020, the first milestones will be counted in 2015 with hopefully 50 new therapies and a diagnostic means for approximately 3,000 diseases.


STEVE USDIN: So, Dr. Wang, part of it must be the idea that you're going to be able to uncover common physiological bases for some of these diseases, rather than having to go at them one-by-one. Is that what you're doing?


DR. LU WANG: That is the hope. The more we know about the genetic basis underlying the rare diseases, the more hopefully we will see the shared disease-causing mechanisms. In fact, we are seeing more and more from the scientific publications, from the researchers in this field. For example, during today's session on rare diseases, we talked about a publication jointly made by two IRDC research groups that was about the defect in splicing, which caused a very rare syndrome by the name of Nager Syndrome.


And that was the first discovery made about that syndrome. But that was not the first discovery made about defects in splicing that cause disease. So that speaks to the shared mechanisms which we hope would shed light on developing drugs that are effective for common rare diseases.


STEVE USDIN: So one of the things you're doing is you're soliciting people who have or might have rare diseases to submit samples, so that you can do this kind of genetic analysis and look at them. How is that effort proceeding?


DR. LU WANG: I will start and Ruxandra will add. And she can speak to the effort the entire consortium has made. The centers of Mendelian diseases are led and participated by experienced researchers in this field and who have established research connections with healthcare professionals. They are also actively reaching out to the research community and the patient group.


And without going into details, in a nutshell, I'll just say that they have a website which explains to people about the goals and abilities of these centers. They also participate in conference meetings, patient groups meetings, and the goal is to make people know about this program. And so that everybody can work together.


We'll get back to our discussion of rare disease research in a moment. First, by definition, a rare disease doesn't affect many individuals. But there's so many rare diseases that suffering from one is not uncommon. Here are some statistics showing how common rare diseases are.




STEVE USDIN: We're talking with Ruxandra Draghia and Lu Wang about the search for therapies for rare diseases. Dr. Draghia, we wanted to start out with you -- we got cut off there -- about what you're doing in Europe to try to recruit patients who might have rare diseases, to be able to diagnose them and come up with therapies. Also, I was wondering if you had any examples of successes that you've had to date in this area?


DR. RUXANDRA DRAGHIA-AKLI: One point that needs to be made is that the international consortium has patient organizations, as members in the executive committee on both sides of the Atlantic. And these are umbrella organizations that are, in fact, putting forward the voices of the patients, but also spreading information and attracting the patients, explaining how research is performed, and what is the value of working with a project for the patients, and with the patients, rather than each researchers and patients taking separate paths. So this is one important point.


In our projects, we do have patients organizations and patients that are involved, in particular, in the projects related to rare diseases, this is very common. I would say that the vast majority of projects in this area have patients that are involved as active designers, if you wish, and where their needs are heard. What we are doing from establishing databases to putting forward information from explaining how research is done to mobilizing the community -- all that is very active in Europe.


STEVE USDIN: And Dr. Wang, can you give some examples -- I know it's too early for the Mendelian Centers to come up with new therapies or even diagnostics, but can you give some kind of update on what you've accomplished and what you see as the next milestones?


DR. LU WANG: Sure. And first of all, I will clarify that the Mendelian Centers are founded to be the research centers to discover the genetic basis of rare disorders. So that is their focus. And their effort will lay a foundation for the development of diagnostic tools and therapies.


In the past 15 months, the Mendelian Centers have worked with more than 300 researchers from a good number of institutions from about 30 countries. They have sequenced more than 9,000 exomes representing more than 320 disorders from all major organisms. And while the analysis is still ongoing from the sequencing data, at this point they have made discoveries of more than 60 causal genetic changes bearing genes. And they have more than 100 candidate disease genes to be further confirmed.


So that is rapid progress that they have already made. And if you think about what researchers were doing before the genomic era, when they had to relay, for example, linkage analysis or targeted gene approach. The discovery process is definitely rapid.


STEVE USDIN: That's this week's show. I'd like to thank my guests John Walsh, Rogerio Vivaldi, Ruxandra Draghia, and Lu Wang. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #biocenturytv. I'm Steve Usdin. Thanks for watching.