Among those speaking at the republican jewish coalitions 2023 Leadership Conference in las watch live at noon eastern on cspan saturday, or online at cspan. Org. Up next, testimony on access to research and treatment for patients with Rare Diseases. Advocates for medical ethics and therapeutic industry professionals also testified to provide insight on the fda Clinical Trial process. This hearing with the Senate SpecialLegion Committee is about two hours. With the Senate Special aging committee is about two hours. Good morning. Welcome to the committees eighth hearing of the 1 18 congress about Drug Development for rare and serious diseases. As is the tradition of the committee, the aging Committee Ranking member, Ranking Member braun in this case, will offer an opening statement. Ranking member braun thank you, senator. I thank the witnesses for coming and for all the folks from around the country who are here today. There are over 7000 rare and serious diseases known to man. Its estimated that 95 lack treatment. In my time as senator, there has not been one Senate Hearing to examine promising therapies for people with rare, progressive, and serious diseases. The room is packed with people that live this reality every single day. Right here, 350 patient stories from 44 states. This is long overdue. People that watch their bodies deteriorate in real time. Family members who have seen their loved one go from the picture of health to knocking on deaths door. Parents who buried their children before they even started school. I want to recognize and thank each and everyone of you that are here in the audience and let you know that this is the beginning of a new day for what we are all interested in. Chairman casey, in response to this hearing, our committee has received these letters. 350 of them, 44 states. With personal experiences. I asked by unanimous consent that we enter this into the record. Without objection. Ranking member braun thank you. A wide variety of disease groups are represented in these submissions, including als, the ipg, extremely progressive pediatric cancer, and an ultra rare genetic disorder that results in death from Heart Failure before a childs fifth birthday. Importantly, none of the diseases that our constituents have contacted us about have any form, have any form of fda approval treatment, not one of them. These diseases are relentless. They are widespread and devastating. Most are considered a death sentence. But they are not invincible. And our constituents are not helpless. Patients deserve a promising pathway at the fda. Today, im joined by senators gillibrand, wicker, kramer, murkowski, and warnock, in sponsoring the promising pathway act. To create a more flexible, accessible, and compassionate drug approval system at the fda. If there is any indication from the over hour and a half i spent on the senate floor, we will be getting a lot more senators on this bill. The promising pathway act will create a rolling, realtime drug approval pathway to speed access for individuals with these Rare Diseases. This bill does not undermine Patient Safety or the fdas Gold Standard for drug approvals in any way. Therapies developed through the pathway will be rigorously evaluated and continuously studied, using real world data. I ask unanimous consent to enter into the record a letter of support for this hearing, signed by 15 individuals and organizations. Without objection. Ranking member braun the promising pathway act is a common sense step to give the fda the flexibility it needs to serve americans with these most trying diseases. The constituents continue to fight for new treatments, greater access, and full eyes. I ask my colleagues join me in unlocking hope for these constituents. I yield back to you. I want to thank Ranking Member braun. He worked to put this together and his staff and our staff, im grateful for your work on this. This is a topic that is meaningful to everyone in this room. We look forward to a robust discussion about this topic today. Rare diseases are those that affect some 200,000 americans and over 7000 Rare Diseases have been identified. While each disease may only affect a small number of people, collectively its estimated that some 25 million to 30 million americans are living with a rare disease. Weve done research into and Drug Development for these diseases. In the 40 years since, we have over 1100 new drugs or new indications for drugs approved for Rare Diseases. I am proud to have worked on legislation entitled the creating hope act to incentivize the development of drugs for rare pediatric diseases, in particular, in other legislation, to address some of the challenges faced by those living with what you might call ultraRare Diseases, which affect an even smaller number of people. My legislation captures what we as legislators are trying to do, to give americans living with Rare Diseases hope for the future. While we have made some progress, many challenges remain, as we will hear from our Witnesses Today. Too many People Living with and dying from Rare Diseases still do not have fdaapproved therapies to treat or mitigate their conditions. I believe every of these individuals deserves access to an fda approved safe and effective therapy. We must make sure that research continues, and that Clinical Trials are designed to allow effective therapies to reach patients as quickly as possible. Rare diseases and the research and Clinical Trials for drugs to treat them are fundamentally different from more common conditions. We will explore some of those differences today and the ways in which they present challenges for Drug Development. Through our witnesses and their testimony today. Its important to note that my observations on the challenges facing the rare disease communities and the community and the steps we might consider to address these challenges dont necessarily apply to other nonrare conditions. But as we will hear today, the challenges for Drug Development start from the earliest stages of development. When Patient Populations are small, its hard for researchers to develop a natural history. And what the trajectory of the disease is when it is not treated. Natural treatments are important for developing therapies, because if you dont understand how a disease progresses, its hard to measure whether a new therapy is working. Rare diseases often are heterogenous, meaning that not every patient disease will progress in the same way, compounding the problem of poorly understood natural histories. Once a promising candidate makes it to Clinical Trials, there are further challenges. Drugs intended to treat common conditions are tested and hundreds of thousands of people. When your entire Patient Population is only a few thousand or a few hundred, or a few dozen, it is simply not possible to do the same type of Clinical Trials. When you have smaller trials, it is difficult to measure efficacy. The agency has done a lot more work to hear directly from patients. More recently, the fda has announced new initiatives, specifically aimed at supporting Drug Developments for Rare Diseases, such as the support for Clinical Trials, advancing Rare Diseases, therapeutics, or start, the acronym start. S. T. A. R. T. This is a Pilot Program to enable realtime communication from the drug sponsor and the fda staff on these development issues. Another Important Initiative of the fda is the rare disease endpoint advancement Pilot Program, to support drug sponsors abilities to engage with the fda around the development of socalled endpoints. The metrics of efficacy. For drugs for Rare Diseases. In the last decade, the fda has done more to hear directly from patients with patient focused Drug Development. These are meetings that give the fda staff the opportunity to hear directly from patients about how their disease affects them and what drug effects are meaningful to them in their daily lives. I support the agencys recent steps. But we should continue supporting and strengthening the authorities. And to do more to facilitate more approvals of safe and effective drugs. I look forward to hearing todays recommendations from our witnesses about the steps we can take to lead to more fda approved treatments for Rare Diseases. Next, we will move to our witness introductions. Im pleased to turn to our first witness, our first two witnesses, who will be sharing their experiences as patients and advocates. But in this case, they will not be answering questions. They will be providing opening remarks virtually, and for our First Virtual witness, i am glad to turn to Ranking Member braun. Senator braun thank you, mr. Chairman. Its my pleasure to introduce brian wallach. From the time we formed our als caucus, ive gotten to know brian well over that time. Really needs no introduction. He is a true changemaker and champion. Brian has a storied career as a Regional Campaign director and white House Counsel for president obama. He later became a federal prosecutor in chicago. His life took a turn in november 2017, when he was diagnosed with als and given six months to live at the age of 37. Rather than accepting the status quo, he decided to fight. Along with his wife, sandra, ryan cofounded i am als, a nonprofit dedicated to curing als. Ryan is a father of two young girls. Thank you for being with us here today, brian. Member bron. Chair casey thank you, Ranking Member braun. Now, i will read and except from senator durbin. I am pleased the senate Agent Committee will be hearing from my constituent, brian wallach. I want to thank the chairman for affording him to share a few words about brian. One of the wonderful things about being a United States senator is the people you get to meet along the way. People like brian and his wonderful wife, sandra. Six years ago, on the day they should have been focused solely on bringing their newborn second daughter home for the first time, this young family was confronted with an unimaginable diagnosis. Brian had als. A disease for which there is no cure and which, as of now, is fatal 100 of the time. Brian and sandra quickly turned their grief into action, starting i am als and galvanizing the als Community Around advocating for increased attention, research, and results for all als patients and their families. Boy, have they had success. Brian and sandra have been the driving force of getting act for als signed into law, ensuring congress doubled the department of defenses als research budget, eliminating the fivemonth waiting period for als patients to get Social Security benefits, and working with the fda to get several new als treatments on the market for the first time in years. And they are not done yet. I hope the aging committee is as inspired by brian as i am, and as i always am, and i look forward to hearing his recommendation for how we can continue to utilize the patient voice to make progress for als families. Thats a statement from senator dick durbin. Our second witness, maureen bell is from pennsylvania. Maureen was diagnosed with a classic i want to make sure i pronounce this right. Galactosemia, seven days after her birth. Thank you, marine, for sharing your experiences and your story with us. Now, i will turn to Ranking Member braun. Sen. Braun thank you. My pleasure to introduce dr. Peggy plewsogan. She is a professor of medicine at the university of virginia hospital. Peggy attended Harvard Medical School and completed residency at peggys husband james was diagnosed with als. She has since become a caregiver and advocate for i am als. Peggy and her husband and two children. Thank you for agreeing to testify, and james, thank you for being here today. The next witness, dr. Anish is of a small biotech firm dedicated to treating rare genetic disorders. He has been with them since 2006. He is a physician with over 20 years of experience in developing biologics, drugdevised combinations and diagnostics, as well as therapeutic medical devices. Thank you for being here today. I will turn to senator vance to introduce the next witness. Sen. Vance thank you, Ranking Member braun. Thanks for the chairman for hosting this discussion. As senator of ohio, i am pleased to introduce mr. Keith. He is the president of a leading International Charity devoted to finding cures for pediatric brain cancers that may help prevent other cancers. He is the president of the Pediatric Brain Tumor Consortium foundation. He and his wife, brooke, established their foundation in 2007 after losing their daughter to dipg at the age of seven. Her public battle was memorialized in the bestselling book notes left behind. Since then, the foundation has invested more than 30 million in over 100 30 trials across 17 countries. Over 130 trials across 17 countries. Keith helped create an innovative organic and link registration that has become a model for other registries. He is advocating on the half of facilitating his work rather than making it harder. On behalf of facilitating his work rather than making it harder. Thanks, keith, for being with us today. Thank you, senator vance. I will introduce our sixth and final witness, Holly Fernandez lynch. She is from philadelphia, pennsylvania. She works in philadelphia but lives in delaware county, correct . Professor Fernandez Lynch is the assistant professor of medical ethics and the department of medical ethics and Health Policy at the school of medicine in the university of pennsylvania. A lawyer and bioethicist by training, professor Fernandez Lynchs scholarly work focuses on the food and drug administration, pharmaceutical policy, access to investigational medicines outside of Clinical Trials, and Clinical Research ethics. Thank you professor for sharing your expertise with us today. And so, we will start with our first witness, brian wallach. And maureen bell will follow him. Mr. Wallach, you may begin. Thank you for the opportunity to testify today. My name is brian wallach. Ive been living with als for six years. Als has changed every part of me. My legs no longer work. My arms no longer work. Als has almost taken away my voice as well, which is why my amazing wife, sondra, is reading this testimony. Als is a disease that is 160 years old. Let me repeat that. For 160 years, als has killed literally everyone diagnosed with it. Everyone. That is simply unacceptable. Today, we hope to reform the fdas approach to diseases like als. Under current fda standards, it can take 15 years or more for effective drugs to move from preclinical work to approval. In the meantime, many people with rapidly progressing terminal conditions, including als, die and have no treatment or options or hope available to them. One of the lessons from the neuron adcom is that there is no such thing as a socalled Gold Standard across the fda for how to approve new treatments for rare or fatal diseases. Instead, todays reality is that whether a treatment will be approved or not depends on what fda center it is in and on the specific individuals in the fda review Team Assigned to a treatment. A second lesson is that the existence of the 2019 fda guidance is not enough to ensure uniform approval standards of new treatments for als. We very, very unfortunately learned this lesson the hard way just a few weeks ago, during the adcom, when the question presented to the adcom did not incorporate the fdas own 2019 guidance about regulatory flexibility. The primary question put before the adcom was, do the data presented demonstrate substantial evidence for effective treatment of mildtomoderate als . This question did not at all make reference to the guidance that stated when making regulatory decisions, fda will consider one, patient tolerance for risk, two, the serious and lifethreatening nature of the condition, and three, and this is exactly why legislation such as the promising pathways act is absolutely critical for People Living with als. There is no fda approved biomarker for 95 of us approved living with als. The result of that is treatments for 95 of People Living with als, including brian, do