An Update on BioMarin Clinical Research and Studies in the PKU Community Barbara Burton, MD, Professor of Pediatrics, Northwestern University Feinberg School of Medicine, Director of PKU Clinic, Children s Memorial Hospital Rob, PKU clinical trial participant Andrew Schorr, Host Shared Experiences, is a Special Edition series focused on clinical trials and PKU, produced by Partners in Marketing in association with Patient Power and sponsored by BioMarin Pharmaceuticals, Inc Clinical Operations Team. Please remember this discussion does not necessarily reflect the views of Patient Power, Partners in Marketing, BioMarin or our partners. Also, remember our program is not a substitute for a discussion with your own doctor. Please consult your doctor for medical advice that s most appropriate for you. Rob s Story Andrew: What does the latest PKU research mean for you? We ll discuss PEG PAL, and other BioMarin clinical studies. What will the future hold for the PKU community? Hear from experts who are directly involved with the research and get your questions answered. It s all next on Patient Power!! Andrew: Hello, I m Andrew Schorr in Seattle. Thanks for joining us! Today we re discussing updates about current BioMarin clinical trials for the PKU community. We re joined by one of the top PKU researchers, Dr. Barbara Burton from Children s Memorial Hospital in Chicago. I always like to begin with someone who has experienced our topic first hand-hand, and today that s 25-year-old Rob from Chicago, who participated in a clinical study. Rob, welcome to the program. Tell us a little bit about why you chose to be in a clinical study. Rob: Well, I ve actually been in a couple of studies. For some reason, even at an early age, I was always very interested in the science behind my PKU. Of course as a 5 or 6 year old, you really don t understand, like particularly for me when my mom would tell me you can t eat certain foods. As I got older, I kept asking questions, and the answers got more in-depth. I used to say to my mom when I was a little kid that if they ever came up with a potential treatment for PKU, I would be the first one in line for it. So when I was given the opportunity to participate in a trial, I jumped at it. I was very fortunate that I really wanted to do it. It s the sense of being able to participate in something I really otherwise would not be able to do. And it s not just the direct impact to me. It s also knowing that I m helping in research that 1
really has the potential to make a big difference for a lot of people, just beyond myself. And thankfully I m in a position right now where I really have that time available to do that in my life. I realize that a lot of people out there who, because of time or geographical restrictions, wouldn t have this opportunity. And it has been a very big time commitment for me. For some trials, they might require you to come in five days a week, and that can make it hard to have a fulltime job and still maintain that kind of upkeep. But at the end of the day, I feel it s completely worth it. Andrew: Well, Rob, you certainly are making an important contribution. I hear you re also thinking about medical school. It sounds like you have a lot of great things in front of you for sure. What has the experience of participating in a clinical trials been like for you? Rob: Well, you mentioned medical school, and the irony of it is that I actually graduated college with a degree in economics and my minor was biochemistry. So, I m still working on getting the experience I need, you know I m a little behind being in economics. With trying to get into med school, I need a little more experience in the field. But I think it s probably that kind of background in the sciences that has helped to familiarize me to really familiar myself with the way drugs are developed and the different phases of clinical research. I really have an understanding of the only way we re able to learn about these kinds of treatments and really develop them is through conducting this type of clinical research. Participating in a Phase I clinical study, the first time the study drug is ever actually used in humans, definitely meant that I had a lot of questions. I really wanted to understand the potential benefits, as well as the side effects, which you know, are going to be unknown at that point. For me, it was also understanding the mechanism of how the study drug was administered and how it was supposed to work within my body. And, again, that s really the science part of me coming out. If I m able to understand what the drug is potentially trying to do and how it s supposed to work, that makes me feel more comfortable with participating in it. And other things I ve taken away from the trial and experiences in it is that organization. You know, I started carrying a backpack everywhere with me that has all my study related items in it because the last thing you want to do is if you re supposed to do something related to the study, you don t want to get stranded somewhere and not have what you need. So, I end up putting reminders for myself around my house or at my girlfriend s place that help keep me organized. 2
And the staff at the clinic has been phenomenal. I would say really the only drawback is the time commitment. But I look at it as I ve really got a lot of time ahead of me, as far as working. So, I ve no reason not to do it. And this is, again, probably the only time in my life that I ll have this much free time to be able to commit to participating in a clinical study. Andrew: Well Rob, I know your participation and commitment is greatly appreciated. For all of us in the PKU community, the tremendous research and progress that has happened over the last decade has certainly been exciting! PEG PAL Studies Andrew: Now, I want to go to you Dr. Burton. You ve been doing this for a long time and have been involved in several studies. How do you feel about the progress? Dr. Burton: That s right Andrew, there is a lot of research currently happening in PKU and it s really a very exciting time to be working with individuals with PKU. There s been a tremendous amount of progress but yet there are still a lot of unanswered questions. So we look to the clinical studies in progress to learn more, as we explore new treatment options, as well as understand better ways of providing care to our people with PKU. Andrew: Dr. Burton, we get a lot of questions from listeners about the PEG PAL studies. Let s start with the basics, for those who may not be familiar with these studies, what s the focus of this research? Dr. Burton: Well, this is an important study because despite the advancements in PKU treatment, we know that there are still many patients who have trouble controlling their blood phenylalanine levels and suffer the consequences as a result, both in learning and in behavioral issues. These are particularly prominent in our older patients, the adolescents and the adults. We had a major advance a few years back when we had one prescription drug approved by the FDA, that being KUVAN, but about half of patients don t respond to that medication so we really need additional treatments to enable us to have more tools in our tool box for controlling blood phe levels in patients with PKU. So, that s really the purpose of the PEG PAL clinical studies. It represents what we d call enzyme substitution therapy. It won t replace the enzyme PAH that is deficient in patients with PKU, but it does provide a different 3
enzyme that is capable of breaking down phe one that is not normally present in humans. So, the purpose of the study is to find out if the study drug, called phenylalanine ammonia-lyase or PAL, works in humans. The study is looking to see if it lowers blood phenylalanine levels and, of course, is monitoring safety of the investigational drug. Andrew: Dr. Burton, what stage are you currently in with this study? Dr. Burton: Well, Andrew trials of potential new drugs typically are run in phases. The first Phase, called Phase I, is really primarily designed to address safety to find out if it s safe to give the drug to people. Based on the results of The Phase I trial of PEG PAL, it was determined that the drug was safe to continue on to phase II studies in people. We are currently in Phase II, where safety continues to be studied very carefully in PKU patients who were receiving repeated doses of the study drug, but at the same time, we can begin and continue to gather more information on how the drug works, on it s efficacy. We re studying a larger number of patients than were studied in Phase I, using different doses of the study drug and at different times to determine what the best way is to give the study drug. Andrew: And when do you expect the PEG PAL phase II study will be completed, and then what happens next? Dr. Burton: Well, the Phase II study is currently recruiting patients at sites across the U.S. and we hope to complete the study by the end of this calendar year, so by the end of 2011. Depending on the Phase II study results, we plan to start the Phase III study shortly thereafter. Phase III is the final phase required before the research can be presented to the FDA and other health agencies for potential approval for commercial use. The ADAPT Study Andrew: So it sounds like people should stay tuned. Now, let s talk about a study that was presented at the ACMG conference earlier this year, and that s the ADAPT study, which stands for A Diversified Approach for PKU Treatment. Dr. Burton Tell us about the study and what you found. Dr. Burton: Well, the ADAPT study is one that was done at 3 PKU clinics around the country, including ours. Really the purpose of the study was to investigate the frequency of learning and behavior problems in all patients in a PKU clinic and to 4
improve care provided by the clinics. What we found is that many individuals were provided additional services for these issues based on the screening test results. Andrew: Dr. Burton, what does that mean for your clinic? Dr. Burton: Well, in our clinic, we ve learned that the old way we used to use to figure out which of our patients were having significant difficulty, just doesn t work out. We were asking them how they re feeling, doing some standard questioning, like: are there any problems at school? Problems at work? Problems with a relationship? But this study has taught us that that sort of questioning in obtaining a history from the patient is really not very effective at identifying the patients who need additional help. When you do a more extensive screening paper and pencil questionnaires, it turns out that many patients will respond yes to some very telling questions, and as we were doing this, then I could go back with the patient and probe some of these issues. We were surprised to find that there are many patients out there having very significant difficulty when we wouldn t have guessed this was the case just from our cursory, initial assessment in taking a history at the patient s visit. So, I think these types of screening tools are very helpful in opening up conversations with patients about some of the issues identified as we really look to identify these learning and behavior problems. It opens up the discussion and it gives us another tool we can use. Andrew: And if someone wants to stay up-to-date about current clinical studies? What s the best resource? Dr. Burton: Really, I think the best way to get more information about ongoing clinical trials is to talk to your PKU clinical team and ask them how you might participate. Many clinic doctors will be aware of what s happening, even if they are not actively participating in the clinical studies, and can refer you to a participating clinic. You can also go to clinicaltrials.gov and search for PEG PAL or PKU, or some patients like to go to the medical literature directly and use pubmed.org. But I think, overall, your clinic is probably your best resource. The PKU 016 Study Andrew: Dr. Burton, it seems, it s really about staying in a conversation with your as a wonderful way to help staying informed. Now, there s another clinical study you re involved in, and that s PKU 016. Tell us a little bit about this study. 5
Dr. Burton: Well, Andrew, PKU-016 is an interesting study involving sapropterin dihydrochloride, which is the same active ingredient that s in KUVAN. What we know about the study drug from the previous clinical trials is that it lowers phenylalanine levels in about half of all PKU patients. In PKU-016, we are investigating whether the study drug improves learning and behavior symptoms experienced by some people with PKU. It s important to understand this because these symptoms may have a tremendous impact on the lives of people with PKU. In addition this is a placebo-controlled study, and there will be a group of patients who receive a placebo or inactive drug, and they ll be compared with the patients receiving the study drug. Then after a period of time, all of the patients will receive the study drug. One of the goals of the study is to evaluate whether learning and behavior changes in people who are on study drug when compared to placebo regardless of changes are seen in their blood phe levels. In other words, does this study drug have an effect on learning and behavior even if the blood phe level is not significantly lowered? During the first part of the study, the participants will not know whether they are receiving the study drug or the placebo. Andrew: Are there any additional BioMarin clinical studies in children with PKU? Dr. Burton: Yes, actually there is one. We are conducting a 7 year study in the PKU pediatric population to determine the effects, if any, on the development of children age 0-6 years who are using Kuvan. It may also provide additional safety information on the use of Kuvan in this age group. We currently have enrolled approximately 55 out of 60 children with PKU in the study, all of these children being responsive to Kuvan, and have followed them thus far for a period of one month to approximately 2 years and continue to collect safety data. Andrew: Dr. Burton, it sounds like you re collecting a lot of useful information that may potentially help in the management of PKU. That s wonderful. Dr. Barbara Burton, professor of Pediatrics at Northwestern University Feinberg School of Medical and Director of the PKU Clinic at Children s Memorial Hospital in Chicago. So, let s go back to Rob. With all of the clinical research happening, Rob what is your advice to those who might be thinking about participating in a clinical study? Rob: You know, for me, when I walk away from it with a sense of being a part of something bigger than myself. And I ve gone into different trials that I ve been in not necessarily expecting the study drug to work but always hoping that it will. And I ve participated in studies where the drug didn t work for me. But for any small 6
chance that I can help the researchers and help them gather more information is completely worth it. Andrew: Well, it certainly sounds like there is a lot coming down the pike for the PKU community and certainly I hope it makes a real difference for patients. I want to thank all of our guests today! If you have questions, please email us at questions@pkuclinicaltrials.com. And remember the best way to stay up-to-date about the latest information about participating in clinical studies is to visit clinicaltrials.gov or talk to your healthcare team. If you have a moment, we d really appreciate you sending us feedback about the program. I want to thank our guests again! Remember knowledge can be the best medicine of all. I m Andrew Schorr. Please remember this discussion does not necessarily reflect the views of Patient Power, Partners in Marketing, BioMarin or our partners. Also, remember our program is not a substitute for a discussion with your own doctor. Please consult your doctor for medical advice that s most appropriate for you. 7