Transcripts For CSPAN Hearing 20240702

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 Special Legion 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 not qualify for acceleration approval. The promising pathways act addresses this issue by creating provisional approval. The promising pathways act is also built in the infrastructure to require drug sponsors to move faster in conducting their phase three trial and getting the fda the authority to remove provisional approval if Additional Data makes clear that that is merited. We support efforts to bring safe and promising therapies to People Living with terminal diagnoses, pending fda approval. We also support efforts to increase spending on researching into the causes of als and potential treatments. But, we do not support saying to this generation thank you for year contribution to research. Now, go home and prepare to die. While academics and bioethicists may have the luxury of debating theoretically what may look like some perfect system, us, People Living with als today, whose lives are literally on the line, we do not have that luxury. And we are looking to you to provide that with the hope that they can live a little longer and maybe even be here to see a cure for als. The key is ppa approval is merely provisional. It affords early access to promising drugs to people with extremely serious conditions who are willing to take risks. It allows additional evidence about the drugs efficacy to be collected during a short two year provisional approval window. Provisional approval can only occur if a drug is shown to be safe and require patient registries to acquire much broader data about a drugs efficacy and safety than can even occur in Clinical Trials. This data, this data will help the fda make even better decisions when it comes to the approval and labeling of new treatments. Moreover, drug sponsors want to obtain full approval of any provisional drug. Other than allowing the use of realworld evidence to submit an application, the ppa does not alter the current fda standards for full drug approval in any way. The als story is slowly changing and with measures such as the ppa, we can make faster changes needed to get treatment to the community, that will allow people such as myself to live longer and to potentially be around to see als transform from fatal to chronic. I want to take a moment to recognize the caregivers and the People Living with als in this hearing room today. We represent the 30,000 americans living with als right now. I hope you or your staff will take the time to hear their stories and why they believe in the need for the promising pathways act. I want to recognize dr. Peggy as a witness, who has been living and breathing with als for the last year and a half. Thank you for your time, for allowing me to be part of this discussion, and for understanding how important the promising pathways act is. I want to thank brian and sandra for their testimony for being with us today. Now we will hear from maureen bell. Ms. Bell my name is maureen bell. I am 51 years of age and i live in pennsylvania. I have lived with galactosemia for my entire life. Shortly after my birth in 1972, i began to show the classic hallmark signs of failure to thrive. Jaundice, repeated vomiting, and weight loss. Seven days later, i was diagnosed by an intern as having classic galactosemia. I remained in the hospital for three weeks. My mom and dad were given a 32page booklet entitled a parents guide to a lactoserestricted diet. They followed this book as i would need to be on a lactosefree restricted dairy diet for the rest of my life. That was the only treatment for galactosemia in 1972. I doubt my parents knew that many more challenges would lie ahead. Following the years to come, they just had me follow a dairy free diet. It seemed everything was working fine for me at the time, but i was getting older and it made me feel very left out when i could not eat the same foods as my peers. Without modern day advances we have today in nutrition, i cant tell you how isolating it was for me. There were many official events i could not attend. My mom tried so hard, always sending me to parties with a special treat, not just for me, but enough for everyone, so i was able to share. Not being able to eat the same cake that everyone else was eating at birthday parties was very difficult as a child. I also could not process information the same way. I always was a below average student and math was my most difficult subject. And still is today. I struggle with making change, leaving tips at a restaurant, and figuring out percentages. I cannot process it. Basic life circumstances became a struggle. Can only and only when i met other People Living with galactosemia, i realized that comprehension issues were similar for all of us. Just as i was slow academically, i was also slow in developing physically. While my friends were going through puberty, i was not having any issues of this. The normal signs of puberty were nothing like late development. I still looked like i was in grade school, physically, as opposed to being in high school. This continued, and this sense of isolation also continued. I began to have unusual symptoms such as hot flashes, night sweats, and mood swings. After a year of experiencing these symptoms and having bloodwork, i was diagnosed at the age of 18 as having premature ovarian insufficiency, which is a direct result of having galactosemia in female patients. This was something that i this is something that i continue to struggle with today. As a result of this diagnosis, i became very reclusive. I wanted no part in dating or socializing like any other 18yearold could. That was the impact of pli. Secondary to having galactosemia , this was very difficult in my 20s. I wanted to be like any other woman at my age, socializing and having fun. However, i was depressed and had a difficult time making friends and meeting new people. There were nights that i cried myself to sleep. At a church event in 1999, i met a man named bill who showed interest in me and started spending time with him. I was very apprehensive about getting involved in a relationship, even though i was 26 years old. The fear of falling for someone only to have to tell them that i was infertile and taking a chance on losing this relationship weighed on me very heavily. However, i finally got the nerve up to tell him. Bill is a pharmacist and his response was priceless. Not caring about my diagnosis and, instead, advising me to take my calcium because i was such a slacker at taking my calcium. What a huge weight that was lifted off my shoulders. We recently celebrated our 23rd wedding anniversary. I was told that having galactosemia is like looking through a window at everyone at a party and they are eating all kinds of foods that i cannot half. Could not have. I could see them through the window and through the glass but could not break it or join them. The same is true for infertility. I can see moms, children and families, but i cannot break the glass. I cannot experience what it is truly like to be a mom. All my life, i have longed to be on the other side of that window. There could finally be a treatment for people like me. And even though it is too late for me, for younger ones who grew up the way i grew up, i spoke at the Drug Development meeting. But our Community Never heard from the fda after that. They had no questions. No clarification. That made us worry they had not taken the time to learn from our work before reviewing the drug. Will they understand that speech issues dont matter to us the same way as cognition and developmentalees do . Some of us have more scary symptoms than the ones i mention, like seizures, kidney issues, tremors, cataracts, neurological impairments, and intellectual impairments. Will they understand that if they ask for another trial, Rare Diseases often dont have enough patients for another trial . Will they understand that if the drug is approved for Something Else rare, our doctors have seen the improvements in our community and will want to prescribe it for us too. The drug is already being studied in other Rare Diseases. Whether it is Government Insurance or through my job, Insurance Companies dont treat Rare Diseases like cancer. So, that is a whole other hurdle. These days, we must fight for approval but also fight insurance too. The Galactosemia Foundation is working hard on both things. And i hope you can help us all. Im learning about what places like fda and cms and congress can mean to me and the others whose lives are impacted by diseases like galactosemia. I dont pretend to understand, but i know that even one person can make a difference. And i want to help the little girls with galactosemia going through isolation, the puberty, depression, and fear the ability to understand the process. If all of you can take my story and help them, it will mean so much. Thank you. Chair casey ms. Bell, thank you for your testimony and sharing your personal experience. We are grateful you are able to spend this time, and i hope you can listen to the whole hearing. We will turn to our next witness. Chairman casey, Ranking Member braun, and the members of the committee, thank you for the opportunity to present to you today. The testimony is reflective of my own views and not intended to reflect the opinions of the university of virginia. My name is peggy plewsogan. I am the wife and caregiver to my husband, jim. We are both physicians. On december 2, 2021, our lives cracked open. Jim was diagnosed with als. At the time, we were busy clinician scholars. Our lives were full with meaningful work, a close family, a community of friends. With this diagnosis, our lives were upended. What i remember from medical school about als is that it is a diagnosis that a physician dreads more than ever, more than any other. Why . Als is a disease that robs a person of almost everything essential to living our lives. The ability to move, communicate, eat, drink, and eventually to breathe. But, the doubleedged cruelty is that awareness and cognition are left intact. People living with als can feel each loss and fear of the next one every moment. Als is 100 fatal. No one has ever survived. Average Life Expectancy after diagnosis is two to five years. When given this diagnosis, patients commonly hear go home, hug your loved ones, and get your affairs in order. People worry about giving patients false hope. I think they dont understand the devastation of having no hope, of simply waiting for the inevitable decline. Both being physicians, we were not naive about als. But having no hope was not an option for our family. Like many als families, we got moving. We investigated Clinical Trials and got involved in advocacy. One unacceptable reality we faced was the disease moves faster than the fda. Amx0035 was a drug in a pipeline that had excellent safety in a phase 23 trial than anything that was currently available. It was denied approval by the fda, who wanted an additional confirmatory phase three trial. This drug is a combination of two drugs that have been on the market for many years, one that was overthecounter. The only way to obtain the medication was to get the one component online and the other from a Specialty Pharmacy in new jersey off label, at the cost of 1500 dollars to 3000 a month. Most of us in the als community could not afford this. Only after fears advocacy did the fda take another look at the data and approve it, thankfully. Over two years after the results of the Clinical Trial were clear. What does that two years mean for an als patient . Two years ago, jim was running races. He was a chief medical officer for a new integrated care network for children across the state of virginia. He started a new program at uva to care for medically complex children. He had a thriving pediatric practice full of kids and parents who adored him. Today, he is confined to a wheelchair. He needs help to eat. He cant roll over in bed or even scratch an itch. Hes losing his ability to speak. Inside the body that is failing him, jim is the same brilliant, compassionate, creative, and loving human being. The courage he displays everyday is stunning. I am jims primary caregiver. The nights are the toughest. Every time jim needs to turn over or adjust his mask to pull up the covers, i need to do that for him. And he needs to somehow communicate that need. Were it not for the support of our amazing grown children, extended family, and neighbors, im not sure what we would do. Als is relentless. What do you think our life will be like in six months . One thing i know, jim needs to be here. He has a new grandbaby and a wedding to attend. As a physician, one of my areas of expertise is reducing errors in medicine. Doctors are naturally focused on getting all the data to get a certain diagnosis before we start treating someone. But we have learned over time that in the rapidly progressive lifethreatening illnesses, delaying treatment while awaiting that certainty can cost someone their life. So, we start treatment while confirmatory data are coming in. I have watched helplessly as my husband lost the ability to use his hands, then his legs, then his voice. In the face of this 100 fatal disease, delaying access to a safe, promising therapy until a trial can be achieved is cruel. Jim and i are old enough to have lived through the aids crisis. When i started residency, there were no treatments and the medical wards were filled with aids patients and their loved ones. Patients dying no matter what we did. And then patients and their loved ones got activated. They fought for more Research Funding and early access to therapies. I watched as each therapy, one by one, turned the disease around. The earliest therapies were less effective and had more side effects, but they saved peoples lives, while new drugs were added and combined together into cocktails. Like those early hiv activists, we in the als community are fighting for more Research Funding. We are fighting for early access to safe and promising therapies. You have the power to change the landscape of als in this congress, transforming it to a manageable and eventually a curable disease. This is not false hope. This is real hope. We need your urgent action and we are counting on you. Thank you very much. Chair casey thanks for your testimony, and thanks for sharing your story and jims as well. Dr. Badnagar, you may begin your testimony. Chairman casey, Ranking Member braun and honorable members of the committee, i am honored to testify at todays hearing. Thank you for hearing me. My testimony is my personal experience over the years. I am a physician by training. My 25 year career at Small Companies has involved developing treatments for cancer, neurological, psychiatric, and other diseases, and for the last several years Rare Diseases. None of my work, including the lifesaving cancer drugs has been as meaningful as working with this Amazing Community of families with children and adults. Many of them are in the audience today. While the challenges across are similar, there is a mortise portion a more disproportionate impact on patients with Rare Diseases. A similar thing is seen in Companies Like ours. Our ability to raise money and continue work depends prominently on regulatory clarity. If the minutes of an fda meeting do not clearly state and cap forward, or if the Company Receives inconsistent feedback, it could be the difference between having money to carry out a trial or giving up on a drug to treat a disease that has no options. Speaking of diseases with no options, pws is a rare and lifethreatening genetic condition, which occurs randomly and affects about 10,000 to 20,000 patients in the u. S. Children with pws are often recognized within weeks of birth. They have an interest in food which increases over time before they ultimately develop the symptoms of hyperphagia. An insatiable desire to eat. The brain telling you you are starving, even as you eat. Individuals affected by pws never feel full and are constantly focused on food and how to get. Left unsupervised, they have the potential to eat themselves to death. Much like a teenager with pws who ran a home, ate enough that his stomach ruptured and he passed away. The only treatment is to restrict access to food, lock kitchens, motion activated cameras and alarms. Families live in the constant fear of extreme outcomes like visits to ers, police intervention, and the need to be cared for in an institutionalized setting. Invariably, there is a need for constant supervision for life. Numerous drugs have been tried, tested to three pws in late stage trials. Each one of them has failed. And Many Companies have been dissolved. Our drug is a once a day pill which was evaluated and approved in a directed study from 2018 through 2020. Ending a few months after the start of the covid19 pandemic. The study missed its primary endpoint, but the analysis of the precovid data showed statistical significance in favor of the drug. Longterm data now up to four years in some patients shows statistically significant and clinically meaningful improvements with the drug. We have been asked to generate additional control data before submitting a marketing application to the fda. We have completed the study, which shows highly significant in clinical benefits, and we hope to submit an nda to the fda next year. We need a Regulatory Framework that recognizes the novel, complex, and heartbreaking nature of diseases like pws. We cannot continue to apply the same regulatory paradigm tall diseases and drugs. To all cash to to all diseases and drugs. Context must play a role. Its amazing to see new options available for people with als in the first approval of a drug. There is also a syndrome where the drug data may not have a promising path forward. Regulatory delays have a real life impact. For Companies Like ours, programs will be cut, some will even shut their doors. Every day, every week, every month, every year, symptoms will worsen. Sometimes in irreversible manners, and patients may die. The fda is and needs to remain the premier regulatory body of its kind. What is desirable is a rigorous regulatory process. One that balances the risk of approving a drug with the risk of having no treatments available for a desperate population. The promising pathway act is a significant step in the right direction. Timelimited provisional approval would allow patients the ability to access potentially lifechanging treatments as additional meaningful data is generated to justify their use. Availability of such treatments would be driven by clinically relevant data, and approval would come only upon rigorous analysis of data generated from patient registries. In closing, i truly appreciate the opportunity to share this story, highlight the significant unmet needs of the rare disease communities and, in particular, the pws committee. Thank you for your time. I look forward to your questions. Chair casey next, we will move to professor Fernandez Lynch. You may begin. Prof. Fernandez lynch thank you. Thank you for the opportunity to inform todays discussion about how best to achieve a goal we all share, helping patients with rare, serious diseases live better and survive longer. My name is Holly Fernandez lynch. Im an assistant professor of medical ethics and law at the university of pennsylvania, speaking only on my own behalf. As you heard, my scholarship focuses on fda drug approval policy, access to medicines prior to fda approval in Clinical Research ethics and oversight. And Clinical Research ethics and oversight. I sit before you as an academic on a panel with experience in a room filled with lived experience. I am not personally living with a rare, serious disease but the sad reality is that Rare Diseases are not rare in the aggregate. Any one of us could find ourselves or our loved ones affected at any time. And like many, my family has not been spared from serious and lifethreatening diseases, including parkinsons and childhood cancer. We all have an interest in these important issues, whether we are suffering today or might be suffering tomorrow. My key message to the committee is that weakening the fdas approval standards risks conflating the essential goal of getting patients access to more drugs that work with the deflated goal of simply getting them more drugs. Of course, we should tolerate more uncertainty when considering drugs for serious diseases. Thankfully, the fda already has expansive regulatory flexibility , allowing it to do just that. The agency is granting accelerated approvals more frequently and more broadly than it has in the past. It has also demonstrated willingness to approve drugs when trials fail to show benefit on prespecified in points. When benefit is supported by just one pivotal study, when trials are very small and when they lack concurrent control groups. Unfortunately, this flexibility is not always met with rigorous confirmation of benefit after drug approval. Which is a concern also raised by the promising pathway act. The proposed bill has some important strengths. For example, it seeks to limit how long drugs with uncertain benefit can stay on the market. And it emphasizes that uncertain drug approvals should always be followed by efforts to collect additional evidence. However, i fear that the promising pathway act would set the bar too low for both provisional approval and later confirmation of benefit. Now, i certainly understand why any individual patient might be willing to pursue access to a new drug, based on relevant, early evidence of a positive therapeutic outcome. The bills proposed standard. The problem is that weak approval standards affect all patients, not only those who choose to take a provisionally approved drug. Company produced evidence about companies produce evidence about safety and effectiveness. If the fda demands less evidence , patients and clinicians will have less evidence. We see this today in the dietary supplement industry. Imagine if what you had available to treat your lifethreatening illness was rows and rows of products, none of which were known to work. Weak approval standards can also entrench poor treatments by making it difficult to study potentially better treatment options. Both because of reduced willingness to enroll and challenges interpreting results when new drugs are compared to unproven ones. The promising pathway act proposes to address these challenges by relying on patient registries. But because registries like randomization and blinding, observed differences and outcomes might be attributable to underlying differences between patients rather than a result of the drug of interest. Instead of weakening fdas already flexible approval standard, the stronger path forward is to address scientific bottlenecks. Fda and others have already taken important steps in this direction. The agency recently launched a program informally dubbed operation warp speed for rare disease, which will provide realtime advice to companies starting at the earliest stages of Drug Development to speedy and successful trials, address manufacturing issues and other challenges. The agency also has a Pilot Program to advance development of new endpoints for Rare Diseases. Its action plan for rare neurodegenerative diseases and its als science strategy improve the understanding of rare disease, enhance trial infrastructure and innovative trial designs to support the develop of better drugs. While the science continues to develop, the best way for this committee to improve access to effective, rare disease treatments is by ensuring Adequate Funding for rare disease research, promoting Clinical Trial accessibility, encouraging use of fdas expanded access pathway, and clarifying the authority to require and enforce rigorous post market efficacy studies whenever it approves a drug with uncertain benefits. Thank you for your commitment to these important issues, and i look forward to your questions. Chair casey professor, thanks very much. Our sixth and final witness, mr. Desserich. Mr. Desserich thank you. The promising pathway and promising pathway act is something i consider vital to our efforts to find the homerun cure for cancer. I am keith desserich. I am a board member of the dipg dmg collaborative. I am president of the Pediatric Brain Tumor Consortium, but most importantly i am a father. My daughter, elena, fought d ipg when she was six years old. We had no hope. There were no trials available. They told us to go home and make memories. She understood this, aware that until her last day that there was nothing we could do. With the ipg with dipg, each day you see your child loses something. One day, it was her ability to see out of her left eye. The next day, it was her ability to speak. Then her ability to walk. Until one day, it became her ability to swallow, to breathe, and her heartbeat. Whats particularly cruel about this type of disease is it affects children and it is very, very rare in adults. But at the same time, many experts believe this is a cancer that can show the most promise at the same time as believing this is a cancer they fear the most. For this reason, it is known as a homerun cure cancer. We have made it our mission to focus on these rare cancers, Building Tools from scratch such as a registry that spans 100 that spans 129 hospitals, intelligent patient tools, Strategic Research and even virtual hospitals, to try to create leverage for all of the great guidance and intelligence we can find worldwide to come to bear on one patient. In the 17 years since alayna lost her fight, we have invested in over 30 million in research and support through 135 projects. I understand the perspectives of the researcher. I understand the perspectives of the parents. I understand the perspectives of the registry. I come to you having seen each of these various elements of it, in addition to talking with parents each and every day, when they are in their last weeks. I also come with hope. I hope for a new way to fight cancer. I believe the fda is wellintentioned. But in the end, no one plans for this type of devastating cancer. Sadly, i believe there is much confusion inherited from bureaucracy. Whether by regulation or guidance clarity, i argue the system is broken and the status quo will not do. For our purposes, there are effectively only two measures that we can consider when we one is expanded access. The other one is right to trial. It is important to know that with expanded access, it is not an alternative for the promising pathway act. I know this, not only from dealing with the loss of my daughter but also in calls with over 200 families per year asking for help, any help in their last and final days. With di pg, a patient is frequently only given two weeks after progression to act. Expanded access requires four levels of approval. 24 hours for a family to reconcile with the news. Three days for a doctor to determine the strategy. Two weeks for an internal review board to approve the methodology. Three days for a Pharmaceutical Company to respond and up to 30 days for the fda to effectively approve the entire process. Thats one week longer than our child survives. It doesnt work. Work. In this right to try. Slightly better of the two level processed to patients and families with an end report model it submits to the fda. We think clarity withing transparency, or cornerstones of being able to find a cure. A storm terminal means months or years to live. They assume theyre not intelligent to make decisions for themselves they assume the data and less than ideal situations are worthless they assume every patient is an adult. The assumptions are wrong. The reality is we do not get doctors who understand the assistance we do not get a call back on the weekend and none of these acts were designed for pediatric terminal diseases. The promising pathway act as differential. Offers an alternative to fda mandated unethical practice of trials given the wrong drug to the wrong patients were pediatric terminal diseases. Right now, nearly every therapy designed for pediatric cancer is guided through a threephase adult trial before we can even get to a terminally diagnosed child. Outlier participants and retains it for the use by the fda the Drug Companies and researchers and patients and any thirdparty registry of registrf substance thus improving transparency. Also addressing Insurance Coverage and Financial Burdens in ways that neither previous alternative has. Finally, promising pathway act advances innovative therapies that may be impossible to subject to current trial design. Keep in mind the trials for the rare cancers rarely ever get leading us to give up on good ideas were enrolling children in trials we already know dont work. It is not lost to me the value of a Clinical Trial but what is lost to others is the value of a quick and efficient Clinical Trial. Unfortunately with rare pediatric cancer we have to consider this and sadly in their final days also compassion. I have a pile in front of me of grants. These are grants that we have worked to build, to fund at many different institutions. Theres 46 of them. This is a pile which has hope, it is the dreams of the researchers and frankly it could be the lives of these kids. This is 46 chances to be able to cure cancer and sadly the whole reason why im here today is i believe that these 46 opportunities to be able to cure cancer may never reach bedside unless we get dpa past. I am a big believer in personal initiative but in this case we may be able to go no further unless government gets out of the way. The promising pathway is how we do this. Families are desperate for another chance at seeing their children go to kindergarten, see their child to get a drivers license, to see them graduate from high school, go to college and get married. We want a chance to see them grow up. Rarely do you have a chance or a bill that asks for no money and it isnt really part of what we are asking for. This is the case when you connect to give patients fighting for the power to save their own lives. I lost my daughter but i refuse to believe that we cannot save hours. Youve heard today from some compelling and welleducated witnesses. Im the only one however that has lost everything in the sand was given no options because there wasnt any. There was existing barriers that were either too cumbersome where policies were built around the majority and while some may appear to be small from the aggregate, it is with this type of cancer that experts also believe that we would have the greatest impact to be able to cure it. So what we may ignore may be precisely what may save us. The promising pathway act may be the single biggest piece of legislation that costs nearly nothing but may change everything about how we win the war on cancer. Thank you. Thanks so much for your testimony and for the story of your family and your daughter. I will now turn to the Ranking Member to begin a round of questions. Thank you mr. Chairman. First question is for ryan if youre still with us. We appreciate your testimony and because of your work how youve got so many people engaged in the cause. And kudos to you for that. What was your risk tolerance for a new therapy that is documented, real world evidence showing advocacy and has received provisional approval from the fda . We come back to brian if he is still with us on zoom. Thank you, senator for your question i have no other option for new treatment other than other than the expanded Access Program or provisional approval that other patients may not to be because i know that if i do not try, i know that if i do not try, i will die thank you. Next question. Thank you for sharing your story. Sorry for the loss of your daughter. Will any current drug approval or Access Programs at the fda address real terminal pediatric cases . I dont. Thats the reason im here because there isnt anything that applies to this. The amount of patients that we talk to they are not getting any answers for medicine or Drug Companies or anything of that sort. Its because of two things. One reason is because of time. We dont have that time. We have two weeks and nothing gets done in those two weeks. Ive had so many times ive seen compassionate use has been approved for a patient that usually comes in several days after the patient has already passed. To talk about a difficult call, thats a horrible call to make. Ive also seen where it doesnt address anything having to do with pediatric. We write walls with the ideas of adults and if you look at these guidelines weve put forth, we grant waivers for them not to do it in pediatrics but we never go the opposite way and so because of that we have to wait and hope that it can go through all of the adult trials first before it can ever get to a child so it never gets started so at the end of the day we cant get access to those drugs. The time is not the right amount of time and the children are being ignored in this and it shouldnt be that way. I do have more questions if you want to go ahead and ask another one. Fda has a variety of drug approval pathways and designations in recent years the agency has begun to take steps towards creating a more accessible and flexible system. However millions of americans with of these diseases lack any fda approved treatments. Could you highlight the hold in the fda drug approval and a Clinical Trial system that your husband is falling through . Thank you for that question. I will mention two. One i think weve heard a lot about today and i want to be clear that is important to me and that a problem that i would like to see solved is that patients that are dying dont have timely access to promising safe therapy. To be clear i dont think anyone you heard speak is suggesting a change to the safety standard. At this is about time and access. To confirm safety and establish potential efficacy and then phase three trials. Obviously no one sitting at this table has had for themselves or their loved ones. The time it takes for these confirmatory trials is simply too much for these particular patients with of these particular diseases, so we want access to promising therapies when early evidence has been established and being confirmed all we want as an alternative is a pathway that allows access to therapies at the point where safety and promising evidence and effectiveness have been established. The second point i want to make theres been talk about the accelerated pathway thats really not available to patients with als at this point at least 95 of patients with als because there is no reliable biomarker in the pathway that requires or relies on biomarkers or surrogate endpoints, so thats another hold of for someone like jim that pathway really doesnt apply. Thank you. This question is on bio biotech risks. Mostly Smaller Companies can be billions of dollars and years to submit and the application to the fda Larger Companies generally dont do it. Tell me a little bit about is the market cooling for this due to the fact that we have a process that is stubborn and bureaucratic. The answer is yes. There are parts of the system that are doing well. Patient advocacy is stronger than its ever been before. The funding environment you can see and engage in the Public Companies with about 30 . This may be the third year in a row. It would be the first time thats the case. Number of Companies Going under have been phenomenal. Number of layoffs have been extraordinary. So, yes was the pathway addressed in a way that would be meaningful so we at least keep this in business when you think of why that is the case i think the uncertainty in the Regulatory Environment with Companies Like mine we work on one or two programs and if you dont have the clarity, then its hard to get the funding to do the work it would definitely help. Thank you, Ranking Member. I will next move to my questions and i wanted to note a number of senators have been here and some will be back. After my questions or appearance we will go to senator scott. Weve also had to senator joe legrand and blumenthal here. Let me go to my first maybe two questions. As a predicate, i understand one of the challenges in rare disease Drug Development as isthere are often very few true experts in the disease and this presents difficulties in the drug review process. The fda acknowledged the challenges and indicated they are open to revising some of the policies to ensure a clinical expertise for rare disease therapy. So heres my question. As you work through the Drug Development process, are there areas where greater expertise and Rare Diseases like you mentioned among fda expertise for that syndrome among others, among those reviewers are there instances where that would be helpful for the expertise . Thank you, senator and yes it would be helpful. When youre dealing with the diseases, we dont expect that there would be at the fda because it is a disease. So we would hope that from the very beginning of the process there would be experts at the other end. Thats not been the case. We generally take physician experts with us. The problem and Rare Diseases which is different from other large massmarket type of businesses is that you generally involve all experts in the Clinical Trial otherwise you wouldnt be able to enroll the trials. If you believe them to be conflicted then who would be the expert so this is one not very difficult thing that can be implemented. You can take their opinions with a grain of salt but consider them to be nonconflicted. Thanks very much. I have one more question before turning over to senator scott. How can the fda ensure its consulting with the is these appropriate disease experts while ensuring transparency around potential conflicts of interest during the review . Thank you for the question. This comes up often when the fda is trying to populate the advisory committees of external experts that often called upon to help them understand various issues related to whether or not they should be approving products as well as broad questions about the Drug Development in particular areas. Fda can waive the conflict is in certain circumstances for example where there is a dearth of experts in different areas they often do waive the typical conflict of interest rules. Theres other ways also as managing conflict. So, for example if you include somebody that has ties with industry or has participated in trials you can also invite additional people to provide their broader perspective. So i think that this is something that is already happening. They are already aware of the challenge. And in fact, it is more often academics like myself that are pushing to be more careful about conflicts than they already are. Thank you, professor and i pi moved to senator scott. First i want to thank the chair and the Ranking Member. I want to thank all of the witnesses. I think everybody in the country has been impacted by a rare disease. I built a Hospital Company and the regulatory hurdles. It was a devastating disease all the money that we increase the Research Dollars on cancer and we got all of our Cancer Centers and everybodys doing research to share their data which to accelerate that seemed to have some impact. We put a lot of money into nih and doubled a budget so i think that we have to do it all of your doing to see if there is Something Better we can do. This is how we get things done by people telling their stories. What can congress do despite the delays that you are seeking . First i want to acknowledge as far as the epicenter, the university of florida has the name Jennifer Miller who sees sees thelargest population in te country. Its true the fda already has the authority needed to provide the flexibility and circumstances we are talking about. There is no consistent application of the flexibility. So i dont know what tool it takes, but i think to mandate the consideration of the regulatory flexibility is valuable and to work with experts to define for a given setting with that flexibility should look like is important and to come up with an enforcement mechanism to ensure that is happening is important. So im not sure what it takes but conceptually that is how we would go about it. 24 of my colleagues in the senate and house asked for change at the fda. Requesting the task force to include leaders from all divisions, offices and centers which process the rare disease therapy applications and examine areas of policy procedural inconsistency and shortcomings to see what we can do better. Also the task force to provide recommendations. The fda to disagree with of the task force that they said they are going to share relevant reports. Theres no accountability and that it doesnt work the way its supposed to work. So the more specific you guys are, the greater chance we would get something done. Does anybody know what kind is collected in the Clinical Trials and how does the fda use that . Does anybody have any ideas . Its in a variety of ways. One of the ways as the patient focused Drug Development meeting where they attend and listen to the Patient Populations about the unmet needs et cetera. During trials, trials like ours we collect the patient information based on questionnaires looking at symptoms and signs that are relevant. If they dont have a lot of fans and their evidence. Realworld evidence is something that theyve been discussing, but its been part of a very small number of applications for approval certainly not the only one approved so far. To add onto that its not fda that is gathering the evidence. Its companies that are responsible for conducting the research but through the patient focused Drug Development program at fda, they put out several guidance documents to promote systematic methodologies and gathering patient experienced data to inform the development of Clinical Trials to make sure that they are asking the questions that are important to patients and systematically gathering information so that it can inform regulatory decisions and having the patient representatives on the advisory committees. Thank you chair. Ranking member. I think from the discussion you have heard today that its clear theres a difference between a broad array of the disease is out there and the places where most pharmaceutical companies go and that with everything we are talking about here its just not being addressed. Especially in the case where one with a narrow window of survival and within the paradigm is to meet bureaucratic and not responding in a way to these over along period of time is there any hope that we can get it done within that current structure. It to the comments that we were talking about about whats being collected and then also comes down to the guidance and the idea that it probably could be done. Is that cold compassionate use in the framework . They could take any of these measures and probably try but it doesnt happen. I think that is the reason why it really needs to be there because otherwise without it, theres nothing thats going to make sure that there is any accountability to deliver the right decisions on it. We witnessed time and time again i talked of Drug Companies and they tell me they cant figure it out. They feel what is in the guidelines versus what is in the guidance with the suggestion that they received back is not matching up. Its not going to focus on our realm and on pediatric drugs. We cant have that. These are small Drug Companies but thats where sometimes the best ideas come from and if we take an opportunity to show those ideas, that is a problem. The data isnt a property of one entity or another. There has to be a patient element to this. That is the beauty of the promising pathway act the registries that allow for everybody to be able to communicate that but still to protect the patients privacy at the same time otherwise we are going to get half of the information and be following what we think is the guidance on it and effectively what we are left with is a wild west type of mentality to how we deal with drug trials and we cant keep doing it that way. Thank you mr. Chairman. I very much appreciate holding this hearing and advancing this important idea. For individuals who are experiencing, the promising of new therapy or a cure provides hope in a profoundly dark time. Thats why ive long described federal support for medical research as one of the best investments that our nation can make and why ive introduced legislation to ensure you that that wefully invest in medical breakthroughs. I want to if i can today talk about a slightly different part of what happens in the drug approval process and im concerned about. I want to talk about how we get research from the lab to the pharmacy. One of the key parts of that as many of the people in the room know is Clinical Trials. Once a promising therapy is identified, pharmaceutical manufacturers have to test the drug for safety and effectiveness which involves enrolling patients in Clinical Trials. Patient displays enormous trust in the people running Clinical Trials. This is why all the Research Involving Human subjects in the United States must be approved by institutional review boards. Professor, you lead work on the quality and effectiveness. Can you say a little bit more about what the job actually is . Yes, thank you, senator for the question. Theyve been required to review nearly all funded research and federally regulated research. They prevent problematic research from proceeding and they also help make sure the science is strong. As i understand this, if a Clinical Trial cant answer the questions it sets out to study or does properly communicate the risks of the study to the people who participate in it, then it is the job of the irb to step in and keep patients safe. But rapid consolidation and a private Equity Ownership of irbs has raised serious questions about whether the boards are leaving vulnerable patients exposed to unnecessary risks. While most are affiliated with universities, the irbs that are not associated with any institution known as commercial are reviewing a larger share of drug Clinical Trials and according to a recent gao report despite representing 2 of the review board now review over half of the studies involving investigational new drugs. The gao reported private equity backed irb is and im going to quote our beholden to their clients or equityholders in other words people that put the money up. Professor, what are the risks that of this creates for a Clinical Trial participants . Thank you, senator warren and i very much appreciate that you pushed to examine this issue. I wasnt surprised by the finding that we still lack meaningful measures of quality. This is something thats come up time and time again and the lack of ability to assess the quality meaningfully makes it harder to assess the different types that is a problem that im working on in my own research. One challenge or concern about private Equity Ownership and profit oriented goals in this space is that it creates a primary emphasis on speedy approvals proposed research and keeping the sponsor happy. They have to compete with them. Now of course speed can be a very good and important thing when we are talking about research we want highquality research to move quickly but focusing on speed can also inhibit deep attention to ethical concerns and it can also limit the focus on maximizing scientific quality and approving science that is good enough and kind of meets the floor of regulatory requirements rather than making sure it is maximally valuable. So that is a primary concern here. Appreciate you raising this. I want to make sure we get this right. The gao found that an emphasis on profits can lead the private equity back to rubber stamp rubberstamppreviews of drug clis and focus less on potential harm to research subjects. While hhs and fda are responsible for inspecting the irb to ensure that participants are protected, the number and the frequency of these inspections has been steadily decreasing. So, hhs and fda needed to step up their oversight efforts in this area and that includes clarifying what it means to be working effectively. Something that these agencies have never done despite decades of requests so that Clinical Trial participants have complete confidence in the scientific integrity of the trials that they join and feeling certain that these have been fully vetted. So thats my concern in the space and why i want to say again thank you to the senator for holding this hearing. I look forward to continuing to fight alongside you for patients. We need to do better in this space. Thank you. Thank you, senator warren. Thank you mr. Chairman. And directing my questions. First, let me just say ive got a 6yearold, 3yearold and 1yearold. My heart goes out to you because i know that youve engaged in this fight because you lost a 7yearold daughter and i know a lot of other folks that lost kids and my heart goes out to you as well. The goal is to get to a society where no parent has to bury their own kid because of human illness that is incurable and i know we are working toward that goal. The worry is given the limited Patient Populations because some of the diseases are incredibly rare and because of how differently we treat pediatric illnesses and the medicines to treat pediatric illnesses we are making some mistakes here. I know there is an argument that the right to try legislation, the expanded access that happened in the last administration which was a good thing that that satisfies some of the concerns that you have with the current way in which we give patients access to the drugs. I would like you to explain maybe why thats not right. What are we still not doing correctly in this space . Anytime we tried within our specific classification, theres been a willingness to make it apply to pediatrics. Right to try it seems to be something that may have some adult applications and i cant speak to it because i dont touch those populations but within the pediatric realm everybody is kind of looked at it and said its not going to go for childrens cancers. That is the cornerstone of everything we are talking about because what we tend to do his thing get along the lines of the ideal circumstances. A Clinical Trial and how these can be perfected and how we can do better with it. All of these acts and regulations are dealing with in perfect scenarios. A Clinical Trial requires things such as investment accrual, time, biomarkers and certainly a completion. The issue is while we all i think see the need for Clinical Trials, we are dealing with scenarios dont exist. We cant get it. Im witnessing a trial that we are putting out there with kids in the disease classification and they have an accrual number of 400 patients. Its going to be 80 years and then we will know whether it does or doesnt work and so you cant think of it in those ways. We have to go into this with the idea we dont have the things to do the Clinical Trials sometimes seemed so promising pathways effectively filled that need. Can you explain to me this particular point so very often ive worked with companies and in my private life, my prior life i should say we work with some Biopharmaceutical Companies and Clinical Trials. One of the things that youre trying to do with these Cancer Therapeutics is identify whether the addition to the therapeutic increases the life of the patient. One of the primary points often times but in some of the diseases we are dealing with extending the time from three months of life to nine months of life is not practical because of the time given for the individual patient for a child is so small so the idea you are somehow going to reach a classic adult endpoint sometimes doesnt make any sense does it . Absolutely not. I think that the community is happy with anything. Theyve added months. Right now i would guess looking at the registry data was expanded by three fold and thats a good but we were only talking about maybe six months. Thats not a life by any stretch of the imagination or whatever be in that case. So its just we have to take it and try to as much as we can. I appreciate that. The last comment we understand we have to do better and talking in this context and others we have a Clinical Trial situation, a Clinical Trial infrastructure in this country that in some ways designs for adult diseases and a very common diseases. And if we dont fix the underlining infrastructure dying not because of therapeutics or the capital to invest because the Regulatory Regime doesnt allow us to actually try these things can figure out whether they work. The other thing for the most part we view our kids as not the same level as an adult. Lets take a drug we know works into some of their cancer and give it a try in kids. Okay for that we can do Clinical Trials and put them out there but what happens most often especially right now for the first time we have an ability to craft the drug that focuses on di pg. But now i cant get it out. I cant get it to the bedside because i cant put it in adults. Adults dont normally get this. The reason for bringing these 46 grants is to impress how important it is because i cant. I want to give a sense of the time constraints we are under now. After senator warnock i will turn and then have one quick question and we will conclude. Thank you much chair casey and Ranking Member for holding this important hearing today. I am grateful for your leadership on this issue particularly its great to work with you on legislation ive heard from georgians across the state that have been personally affected by rare and serious diseases from als to many others and despite the differences in these diseases, theres one thing they have in common. Thats why i was proud to cosponsor the promising pathway act. Thats good Public Policy and it would help patients with lifethreatening diseases receive early access to promising treatments. How would the promising pathway act improve access to lifesaving treatment for those that have serious diagnoses and i ask this recognizing that youve been personally impacted by this. Let me thank you for translating the pain and power and being such an important force on this. Your experience how would the promising pathway act help . I think that its a question of time and direction towards pediatrics. Everybody looks at this with a promising pathway. I have something that satisfies the safety requirements and we can try to move it to words giving the conditional approval so we are moving that up and that helps any patient in the terminal diagnosis. With regards to the pediatric side of things, what promising pathways does better than others is it allows it to move faster into the pediatric realm of byte especially in those rare and terminal cases. Thats not all cases. Theres also specific definitions of what is the terminal case that provides clarity to it but short of that, we cannot get it there. The cancers that we are dealing with are absolutely nothing close to ideal. It changes everything. Can you discuss some of the advances that the patient focused Drug Development program had provided . Fda has a formal program called focused Drug Development its worth acknowledging the major stride of the agency made over the past several decades starting with hivaids advocacy pushed to help recognize patients deserve a seat at the table. It refers to a systematic approach to ensure that they experience and meaningfully incorporated into both Drug Development and the fda evaluation of drugs because it recognizes that patients have expertise in the diseases that they are facing. Its important to hear from patients and its stated that it needs to hear from patients about Clinical Trial design and what are the endpoints that are meaningful to them what makes them feasible. I hate to interrupt but im out of time and a little bit. Do you have an example that you could share . Its a variety of documents to help Companies Understand how to systematically collect information that will be meaningful and they also have a program to develop clinical outcome assessments which are also intended to be specific endpoints that are meaningful and in addition to the patient focused Drug Development program, theres been further incorporation of patient voices on the advisory committees. Before my last question the senator from alaska wants to enter in, senator murkowski wants to enter into the record by unanimous consent last question so often you hear folks have to leave the country to get leadingedge treatment. Thats a shame. We should be that leadingedge and have a system that accommodates it. Could you talk about the difference between our system and one that seems to be working better that would be in europe. If thats better we should at least be emulating that. Thank you, senator its a good question and i think its debatable which one is better. I think its true that there are certain. There are delays that are unnecessary and approving drugs early in the process where we dont have the same considerations. The accelerated approval pathway has been existing in the u. S. On two constructs. One you have a known biomarker or surrogate and a second as a clinical benefit that predicts ultimate youth. The challenge with both of these is that neither of them is present in most rare disease situations. Last years approvals six were accelerated. Five for oncology drugs and one was nonmalignant. At the point is that oncology is an area where they are really well understood and others we could not use the pathways. Theyve defined a certain things that they can do on a regulatory site and negotiate a study prior to approval. We dont have the same provisions. I have one more question we have to wrap up. It is certainly understandable for an individual patient to be willing to risk substantial uncertainty for themselves before better evidence becomes available and a via the expanded access however weakened approval standards affect all patients. Can you talk about the balance that i know we all want to strike from the ethical perspective the balance between the needs of the patients when not all have the same needs or the same level of risk tolerance. One of the things ive heard is if patients dont want to take the provisionally approved drug then that is absolutely true but it becomes more complicated because when you lower fda approval standards that tells industry this is the bar that you have to meet. When the bar is lower than industry responds accordingly. What that does is push back to patients and clinicians the need to make decisions without evidence. Thats why the dietary supplement example is salient. That isnt what people that are facing these terrible diseases need. The other challenge is when the standards are low and you allow products on the market that have not demonstrated that they are beneficial. It makes it difficult to approve those studies and then you might also find yourself having to test new interventions against interventions that have not been proven to work and so you cant quite tell if they are benefiting from this new drug words that neither of these are beneficial so they have to account in its Public Health responsibility not only for the interest of patients today but also the broad population of patients which is why im encouraging the committee to draw on what weve heard about challenges to the expanded access pathway. That is the avenue that needs to be improved and provides this balance allowing patients today who have high risk tolerance to take unproven medicines while we continue to gather rigorous evidence. However the patient registries are not going to get us there because they are not randomized, not controlled, they are not going to be able to answer the questions in the way patients need to make all thomas and informed decisions about their treatment. We are going to close statements i have been working on this for most of the five years ive been here in the senate and i come from a world where within the logistics and distribution business sometimes when you want to get from here to there. I think we have had a really good discussion with it today and weve heard most importantly from folks that are suffering through it and one lesson to learn we need to have more of that even on other diseases. Here the urgency is even more compelling. This is a bipartisan effort after much work i think it is going to cascade into something quicker than what most bills take. In the face of such cruel diseases a more compassionate and flexible path has got to be there for patients. Why does europe have such a pathway and we do not . I look forward to working with my colleagues to speed up access for individuals with these diseases while maintaining the Gold Standard of the fda. We can do both at once. This is not a republican or democrat discussion. This is a human discussion. We all have stories that are deeply personal seen firsthand the impact on how these diseases were averaged not only the victims and the families. To turn passion into action, and we are going to do so. Thank you, mr. Chair. Thank you very much. As weve all heard today from patients and Family Members who are desperately awaiting hope, awaiting a treatment we also heard today from patients whove lived their whole lives without any therapy for their condition. We heard from the caregiver perspective spouses, Family Members, father who lost a daughter hearing how hard it is to watch a Family Member suffer with no treatment options. Weve also heard about the challenges the Drug Companies face when working to bring a drug from a rare disease to market. Weve heard about how to balance the unique challenges posed by Rare Diseases with regulatory processes that uphold to the Gold Standard. We must continue the discussion with each other in the senate, with the fda and all the families represented here today. Weve got to substantially improve the process for getting new drugs to patients while maintaining standards of efficacy and safety. I want to thank all the Witnesses Today for their contributions, for the time they spent here and for sharing very personal details about your life. That is not easy to do in a public setting. The hearing record will be kept open until next thursday november 2nd. Thank you all for participating in this hearing. This concludes our hearing. [inaudible conversations] announcer heres whats coming up tonight. Our book tv program after words is next with martin baron. Martin baron talks about leading the Washington Post as executive editor under the ownership of jeff bezos, and during Donald Trumps presidency. The ambassador to the u. S. Gives a keynote address on their latest development in the war against russia, and later, war journalists share their experiences in reporting from ukraine amidst russias invasion. Announcer cspans washington journal, involving you to discuss the latest issues in government, politics and Public Policy. From washington and across the country. Coming up saturday morning, we look at recent legal challenges to social Media Companies over the claims that the apps impact youth mental health. And we will speak with the host of the president s inbox. Join the conversation live at 7 a. M. Eastern saturday morning. Announcer cspan is your unfiltered view of government. Funded by these Television Companies and more, including midco. No one can do it like we do announcer midco supports cspan as a public service, along with these other television providers, giving you a front row seat to mocracy. Announcer now on book tvs after words, martin baron talks about leading the Washington Post as executive editor under the ownership of jeff bezos, and during donald um