Hearings to examine FDA bureaucracy, focusing on regulator to roadblock.

Good morning. The US Special Committee on Aging will now come to order. Today we're here to ask a simple but important question. Is the FDA doing everything Congress intended it to do to quickly get safe, effective treatments to patients with rare diseases who cannot afford to wait? thirty million Americans living with a rare disease making sacrifices every day is just a part of life. But something they cannot afford to give up is time. Time means the ability to walk. Time means independence. Time means being able to speak, eat, or even recognize a loved one. And too often time is exactly what patients lose while therapies sit in regulatory limbo. Growing up I saw firsthand how rare disease can affect a family. My family didn't have health insurance and my brother had a rare hip disease. My mom had to drive two hundred miles round trip just so he could get the care he needed. She made that sacrifice because care couldn't wait. My brother couldn't afford to sacrifice time. Congress has been clear. On an overwhelmingly bipartisan basis, we have given the FDA flexibility to move faster for parents' patients with serious and life-threatening conditions. The twenty sixteen Congr- in twenty sixteen, Congress passed the twenty first century Cures Act. In that bill and other bills that followed, Congress gave direction to the FDA encourage the use of real-world evidence, highlighting that rare disease drug development requires adaptability and urgency. These laws were meant to help cut through bureaucratic delays and give patients access to the care and cures they so desperately need. But here we are, ten years later, hearing from patients, physicians, and drug developers that the system is not working as Congress intended. I've heard from Commissioner Makkari that he is working hard to fix long-standing problems at the FDA. And I want to thank him for the work he is doing to try and make a strained system work better for patients. However, advocates here today will describe inconsistent review practices, shifting standards, and redundant, often late appearing data requests, that in many cases may not be driven by safety concerns but, but by an overly cautious and rigid approach approach that puts bureaucratic process ahead of patients. As we will hear, the human cost of this regulatory slow walking is real. Many of the patients affected by these delays have no other treatment options. Patients from every state come, come and talk to our offices, and I'm sure the same thing with the ranking member, sharing their irreversible declines in health that happen while they or someone they care about waits for a treatment that that might never come. It's heartbreaking to hear from families who are left watching their loved ones deteriorate. while promising therapies remain stuck in review. Meanwhile, small biotech companies struggle to survive years of uncertainty even when their science is sound. Beyond individual patients, there are serious national security consequences that come with the FDA's inaction and delays. Our adversaries have been accelerating their drug development and approval, attracting investment, talent, and clinical trials. FDA inaction here at home creates an economic and national competitive issue. Let me be clear. This hearing is not about weakening safety standards. Safety must always come first. But safety and speed are not mutually exclusive. A system can protect patients while still acting with urgency, transparency, and common sense. Some of you may be asking why the Senate Aging Committee is tackling this issue when so many of those impacted by issues with rare disease treatments are young. Here's why. Part of caring for America's aging population is making sure that more Americans are given the opportunity to grow old. It may sound cliche, but we are all aging. And if something is standing in the way of a younger American making it to their senior years, that is absolutely the business of this committee and something we need to try and fix. It's my hope that today's hearing will serve as a useful tool to help us understand what we can do to bring accountability, transparency, and efficiency to the process. We are joined by incredible panel of witnesses here today, representing a wide range of perspectives, but all working toward a better future for people living with rare diseases. Now we have a lot of members in the crowd uh that are here because uh rare disease um drug uh drugs are very important to them and I wanna thank everybody for being here. Now I'd like to recognize ranking member Gillibrand for her opening statement.

Thank you Chairman Scott, I really appreciate you calling today's hearing, uh and thank you for our witnesses um and the advocates who are here uh for rare disease day on the hill. It makes a big difference that you come together to make sure your loved ones are being heard and that this challenges and struggles that you go through as families and supporters are being understood by lawmakers. Um, every one of us in this room today, uh, knows that when we have a friend or a loved one or a family member who has a rare disease, that the most important thing is finding a cure, getting the treatment, and making sure they survive. A disease is considered rare if it affects fewer than two hundred thousand people. But rare diseases actually aren't that rare. One in ten Americans is living with a rare disease. And as you know, many of these patients face substantial unmet medical needs. Because it can be really difficult and expensive for companies to develop these treatments and the FDA to evaluate them, Congress has provided the agency with significant regulatory flexibility. to encourage both biotech innovation and rare disease therapies. These include the authorizing the accelerated approval pathway to speed up the drug review, establishing programs like the rare disease endpoint adv- advancement pilot to bolster novel endpoint development, and strengthening, expanding the use of patient experience data and real-world evidence in drug reviews. These mechanisms are designed to help prove access to novel treatments for our patients. And they're supposed to provide drug sponsors with a predictable and consistent approach to addressing regulatory science challenges that are unique in rare disease therapy development and review. Like designing complex clinical trials, developing appropriate endpoints, and using real-world evidence. But it's not working how it should be. FDA's approach, transparency, and flexibility varies widely between its offices, divisions, and centers. We've seen a pattern of hesitation to use authorized flexibilities, limited communication with drug sponsors, failure to incorporate patient experience in real-world evidence reviews, and FDA shifting its regulatory position on trial design at the last minute, rejecting drug applications, and requiring new clinical trials the sponsor may be unable to perform. This is heartbreaking for patients, and it's why we can't afford delays and disruptions in treatment. Rare diseases can progress rapidly, cause irreversible harm, and in some cases premature death. This is also frustrating for drug sponsors who face increased costs and delayed timelines that impact the viability of their clinical trials, particularly in the United States. Uncertainty shapes behavior across the biotech ecosystem. Without consistency and predictability, drug sponsors will continue to struggle with seeking FDA approval and will take their clinical trials elsewhere, like to China. This is bad for business and it's bad for patients. If we want the US to remain the global leader in biotech, and we want American patients to have access to these novel treatments, things need to change. Congress must hold the FDA accountable. We must make sure FDA fixes its inconsistent and unpredictable application of regulatory flexibility. It's essential for supporting innovation while upholding the highest standard for safety and efficacy in the approval of these rare disease drugs. And FDA appears to be moving in the right direction. With the rare disease Evidence Principles, the Rare Disease Innovation Hub, proposing new pathways for approval and try and try and trying to hire more reviewers. But it doesn't matter what agency leadership puts in a press release, it's about execution and implementation across all levels of that agency. Consistency from top to bottom. And Congress will ensure that happens. By conducting oversight, encouraging application of authorized flexibilities, and providing adequate resources to restore agency capacity. I look forward to hearing from our witnesses and working with this committee to hold the FDA accountable because rare disease patients cannot wait.

Thank you, ranking member. I'd like to welcome our witnesses, experts who are here to talk about how serious this issue is and the steps we can take to ensure patients with rare diseases are not left behind by by Regulatory Delay. First I'd like to recognize Annie Kennedy, Chief Mission Officer at the EveryLife Foundation for Rare Diseases. Miss Kennedy is a nationally recognized leader in rare disease policy and patient advocacy and works directly with patients, caregivers and families navigating the drug development and approval process. EveryLife represents the voices of rare disease communities across the country, and has long advocated for patient-centered policies, regulatory flexibility, and timely access to lifesaving therapies. Thank you for, thank you for being here and please begin your testimony.

Thank you, Chairman Scott, Ranking Member Gillibrand, and distinguished members of the committee for convening this critical hearing. I am Annie Kennedy, Chief Mission Officer for the EveryLife Foundation for Rare Diseases. I'm honored to be here alongside the hundreds of advocates who've joined us for Rare Disease Week on Capitol Hill. Collectively, we are representing the more than thirty million Americans living with rare diseases. Today, there are more than ten thousand known rare diseases, about seventy percent of which start in childhood. For small patient communities facing progressive diseases, time is a commodity. Traditional large placebo-controlled trials are often neither feasible nor ethical when considering the challenges and urgency of rare disease. Beginning with the passage of the Orphan Drug Act in nineteen eighty-three, your leadership has provided tools that have rocketed the US into the most competitive developer Each landmark loss since has reshaped our landscape. In fact, tomorrow marks an anniversary of another watershed moment for our community here on Capitol Hill. The MD Care Act hearing, convened in this exact same hearing room, presided over by Senator Arlen Specter, included a thirteen year old named Benjamin Cumbo. Twenty five years ago, I watched with great pride as Ben asked Congress for actions that could help cure him and his friends so that he could achieve his dreams of growing up, having a girlfriend, and serving his country. And Congress did respond. In that time, Congress has built a framework that incentivizes rare product development, authorizes regulatory flexibility, creates new pathways to approval, and embeds patient experience into review. While fewer than five percent of rare diseases currently have an FDA-approved treatment, nearly fourteen hundred orphan-designated therapies are now changing the lives of patients and families. But recently, this momentum has shifted. We are here today because our community has experienced worrisome trends with devastating consequences. While we are heartened by recent announcements of therapy development initiatives, such as the Rare Disease End Evidence Principles Framework and the Plausible Mechanism Pathway and are eager to work with the agency on their implementation, Our rare disease community has experienced a series of product application actions that seem mis-aligned with these recent public pledges to expand the use of r- regulatory flexibility. Since the start of twenty twenty-five, we have seen at least twenty-three complete response letters declining to approve rare disease therapies many under accelerated approval that suggest a hesitation to apply regulatory flexibility through surrogate endpoints natural history studies and external controls. At that same time, advisory committee meetings for drugs and biologics declined by sixty-five percent, compared to twenty-twenty-four, reducing opportunities for external expertise and patient insights to inform complex rare disease product decisions. We asked families who'd been personally affected by recent regulatory decisions to reflect on their impact. These stories will be shared for the record. Story after story spoke to chilling consequences of recent regulatory delays and clinical trial hurdles. As one mom shared about her son, Stone. "My son is now receiving this experimental treatment and he is thriving. For the first time since his diagnosis, his doctors have told us with this treatment a near normal lifespan is within reach for a disease that once came with a teenage expiration date that is nothing short of extraordinary. But we are now living in fear. not because science failed, not because companies stopped fighting rare disease, but because of regulatory inconsistency. We are here today because congressional action is needed to ensure that this generation of patients will benefit from our existing rare disease treatment pipelines. We ask that Congress engage FDA to clarify its approach to accelerated approval for our diseases, its consistent application of regulatory flexibility, and to the resumption of advisory committee meetings so that external expertise informs complex reviews. We also urge Congress to resource the rare disease innovation hub, to strengthen cross-center coordination, and to establish the Rare Disease and Condition Advisory Committee and a science-focused drug development initiative. In closing, twenty-five years ago I stood in this room filled with rare families. Today, advances in science have put life-altering treatments within reach for many. But those advances were not in time for those who were in this room with me twenty-five years ago. While Ben achieved many of his dreams, he died two days before receiving his master's degree. We now have the opportunity to ensure that this generation of rare disease patients will benefit from today's therapy development pipelines. Each time a promising therapy faces delays or demise, investment wanes, future scientific promises unfulfilled, and lives are lost. Time is the most precious commodity for our rare disease community. And as Stone's mom implored while writing from his hospital bedside, "We are closer than ever to rewriting the future of these diseases. Please, don't let my generation become the next group of mothers who stand at gravesides instead of graduations." Thank you.

Thank you. Thank you, Miss Kennedy. Um, now I'd like to introduce Doctor Jeremy Schmauman. professor of neurology at harvard medical school founding director of the ataxia center at massachusetts general hospital and principal investigator for the laboratory for neo-anon anonomaly say about right and he is a leading neurologist who treats patients with progressive and neurodegenerative diseases where time and access to this treatment to treatment are critical he has seen firsthand the consequences of delayed access to care and the irreversible loss patients can experience while waiting for regulatory decisions. His testimony will ground today's discussion in the real-world clinical impact these regulatory delays have on patients and families. Thank you for being here. Please begin your testimony.

Chairman Scott, Ranking Member Gillibrand, members of the committee, thank you for convening this hearing and for the opportunity to testify and for your remarkable opening statements. My name is Jeremy Schmarman. I am the and Robert Fogelman, Chair in Ataxia and Cerebellar Neurology at Massachusetts General Hospital, and Professor of Neurology at Harvard Medical School. I started the first Ataxia center in the country, and I've cared for patients with Spinal Cerebellar Ataxia for forty-five years. I'm the Site Principal Investigator for Bioheaven's study of true in Ataxia. And my comments today reflect my personal and professional opinion, not necessarily that of my employer. Senators, please help us fix the FDA. It has rejected Troriluzole, a drug that is safe, the first treatment to improve quality of life and slow progression in spinal serrbalear ataxia. My patient Steve, for example, developed spinal serrbalear ataxia type three, also known as Machado-Joseph disease, in his late thirties. Like his mother before him, he will become increasingly disabled, will need to use a wheelchair, become bedridden, and die young. But since starting Troriluzole a year ago, he has not changed. Mary, in her late forties, has type two. After six and a half years on Trirubizole, she has not changed. These inherited neurodegenerative diseases worsen inexorably. And in this business, staying the same is success. Like other rare diseases, ataxia is difficult to study, deteriorates slowly, and manifests differently, even within families. There are fifteen thousand ataxia patients in America. Some affect hundreds of people, some just a few. Now, Congress, as you've told us, recognized these challenges and passed legislation mandating that FDA use regulatory flexibility and real-world evidence, in rare diseases like ataxia. The drug Riluzole, used to treat ALS for thirty years, was reported to improve ataxia. Based on this, and the plausible mechanism of action in spinocerebellar ataxia, Biohaven developed Trorulazole, which metabolizes into Rulazole but is taken once a day with better brain penetration and fewer side effects. Early in the drug's development, a taxi patient who stopped treatment after a year of open-label therapy insisted they go back on Trulazole because they told us their condition worsened after stopping the drug. So Biohaven, to their credit, provided Trorulazole to these patients and ran a one-year double-blind placebo-controlled study. Patients with spinal cerebellar ataxia type three improved compared to placebo. They were falling less and they had fewer injuries. So, Biohaven requested approval of Trawilizole for spinal cerebellar ataxia type three, based on these results. The FDA refused to review the new drug application. So, Biohaven obtained FDA feedback and used a revised protocol to follow patients on drug for another three years. comparing them with patients in two natural history studies. In this real-world evidence study, Trorulizol showed significant improvement across nine pre-specified FDA endpoints, slowing disease by fifty to seventy percent. This is a dramatic result that was supported by patient and physician feedback. We were all shocked when FDA denied approval of this safe drug that makes people better. I wrote six letters to FDA leadership between two thousand and twenty-three and two thousand twenty-five, co-signed by seventeen Ataxia colleagues, asking FDA to review the application again and work with Biohabit to make the drug available, if necessary, performing post-marketing studies. I never heard back. Now, three hundred patients, stable on Troglozol, will have to come off drug, and they are distraught. I met three times with FDA's Center for Drug Evaluation and Research. On each occasion, they did not heed the patients or the experts or consider the science. One panel member said to me, " Why should I listen to you?" The FDA's proposed path forward is another placebo-controlled trial that will take five to eight years or a randomized withdrawal of drug from patients benefiting from it. If this happens, patients on placebo will die. I believe this to be unethical, lacking charity, mercy or kindness. Senators, please, save our patients' lives. Use your authority to require that FDA consider real-world evidence and applies the regulatory flexibility you have legislated, and in so doing, restore transparency, integrity and competence to the agency. Thank you.

Yeah, I'd like to recognize our thank you member. Yeah, Jill Bryant to introduce our next witnesses.

Thank you, Mr. Chairman. I want to introduce our next witness, Bradley Campbell. Mister Campbell is the President and CEO of Amicus Therapeutics, a biotechnology company focused on discovering and developing new medicines for people living with rare diseases. During his tenure at Amicus, he led the global commercialization of Gallifold, a medication used to treat Fabry, uh, to treat Fabry disease in adults, which was approved by the US Food and Drug Administration on an accelerated basis. Mister Campbell brings over twenty years of experience in the rare and orphan disease fields. You may begin your testimony.

Thank you very much. Chairman Scott, Ranking Member Gillibrand, the rest of the centers on the committee, uh, it's my privilege to be here today to speak to you about our experience in developing drugs for people living with rare diseases. I'm also honored to be here alongside my fellow panelists. I feel, uh, far less qualified than they to speak today. But I hope I can share some perspectives on the challenges and opportunities we have to help fix the system. I have had the privilege to work at Amicus for the last twenty years, and have dedicated most of my professional career to developing new treatments for people living with rare disease. And I thought I could begin with a patient story that I think captures the spirit of the testimony here today and the conversation we're having. At a recent patient meeting we were discussing patient experience data, and how we might make endpoints for clinical trials more meaningful for patients. And during a break, a young woman with Pompe disease took me aside and said what would be most meaningful for her is if she could breathe on her own for just one minute. That would make the difference between her life and her death. This is not an approvable endpoint in Pompe disease, of course, but she depends upon a mechanical ventilator to breathe. If that ventilator fails, if the battery dies, if an aide fails to clear a mucus plug, just that sixty seconds of her own breath could make the difference between her life and her death. I think that comment is a very powerful reminder to why patients and caregivers must help us design better clinical studies with real endpoints that make a difference for them. We can't ask patients to wait for years before approved treatments come, when the difference between life and death can be that single breath. I think the rare disease innovation ecosystem in the United States has made enormous progress over the last twenty years. But it must now again adapt in speed, agility, and flexibility to keep the pace of innovation. One of our own development experiences at Amicus, I think, sheds light on how regulatory flexibility and working together with sponsors and regulators can make a real difference in drug development. When we were developing our medicine Gallifold for Fabry disease, we would learn in early studies that in some patients the drug worked, in some patients it didn't. Through careful data analysis and close collaboration with the FDA and regulators around the world, we developed an assay that could identify which of the thousands of genetic variants that cause Fabry disease might best respond to the therapy, and just as importantly, which ones may not. The FDA ultimately incorporated that assay into our label and proved the first ever oral precision medicine for people living with Fabry disease. So what does that mean? That means when sponsors and regulators work together, the result was an oral treatment option that has saved thousands of patients, years of bi-weekly infusions. We know rare diseases are biologically complex. We know they're difficult to study. As we sit here today, ninety-five percent of the more than ten thousand known rare diseases lack an FDA-approved treatment. I think that's statistics many of us are familiar with. But if you fast-forward that pace of development, it will take us one hundred and fifty years to only treat half of the remaining rare diseases. Small and mid-sized biotechnology companies like Amicus, Biohaven, and others are the engine of rare disease innovation. But they can only succeed if the regulatory system adapts along with unmet medical need. I think there are three practical areas that we can work together to improve that very system. First, we must start clinical trials faster. We know in other countries, those trials start in weeks, not months. We can reduce administrative requirements, leverage single uh IRBs, use AI and other digital tools to get into the clinic faster. We also must find better ways to measure efficacy. We can use biomarkers, innovative endpoints, accelerated approvals. These are things the FDA has at its disposal right now, but we must use them more. And we can make manufacturing inspections and rules work better. The single biggest delay oftentimes is inspections from getting patients access to medicines the FDA has tools like remote interactive inspections and relying on global regulators to reduce that inefficiency. And let me close with just one final story. At a patient meeting last year, a man with Fabry disease told us when he was diagnosed in his thirties, he stopped saving for retirement because he thought there was no reason to think he could live that long. Fast forward fifteen years, Fabry disease is now a treatable disease. Advancement in treatments have changed that trajectory, and for the first time he's thinking about a future he thought he would never have. I look forward to working together with the members of this committee, and indeed with the regulators, the broad community here focused on rare diseases to find ways to ensure that we have a flexible, adaptable, agile regulatory system that can keep pace with modern innovation. Thanks so much for the opportunity to testify and I look forward to taking your questions.

Thank you, Mister Campbell, I wanna move to introduce our next witness, Doctor Kara O'Neill. Doctor O'Neill is the Co-founder and Chief Science Officer at the Cure San Filippo. uh the Cure San Felipe Foundation, dedicated to accelerating scientific development on disease and empowering families with the resources they need to a- navigate their journey. Doctor O'Neill founded the foundation after receiving her daughter, Eliza, San Felipe's diagnosis in twenty thirteen. At that, at the foundation Doctor O'Neill leads patient-focused research efforts in awareness, working to bridge the gap between scientists, clinicians, industry, and family. She was awarded the International Twenty Twenty Patient Advocacy Leader Award by World Symposium for her exceptional contributions. You may begin your testimony.

Thank you, Chairman Scott, Ranking Member Gillibrand, and members of the committee. On behalf of fifteen million children with rare diseases in this country, I thank you truly for your concern. I'm Kara O'Neill, Chief Science Officer at Cur San Felipe Foundation, a pediatrician, and mom to eliza who has an ultra-rare genetic disease called san felipo syndrome or mps three one of many forms of childhood dementia leading to progressive irreversible brain damage i'd like to first acknowledge the critical public service the fda and its um uh staff who shoulder complex and heavy workloads everyday we know the pressures are significant because we feel it too Of late we've seen many press releases highlighting new FDA policies and programs, which encourage us to look out into the future with hope. But today the committee has called us here with the recognition that current regulatory barriers are significantly impacting patients right now, and never more starkly than for degenerative conditions where time is the most crucial factor, and where every regulatory flexibility must be leveraged to meet this uniquely urgent need. We can see this illustrated in a story of three girls with the same deadly disease, but very different lives. Isabel, or Izzy, was the first child with San Felipe that my husband and I met after our own daughter Eliza's diagnosis. Izzy was just eleven, and the disease had already taken a tremendous toll. She could no longer walk independently, taking only a few steps if her mom held most of her weight. Izzy had lost the ability to speak years before, and could no longer eat or drink without choking, so relied on a feeding tube. She had seizures and increasingly severe abnormal movements that twisted her arms and legs into painful positions. And during one visit, Izzy's mom shared that she'd come to accept this disease would take her daughter's life. But what she said next has always stuck with me. She said, " In truth, I fear her suffering more than I fear her death." At that time, my Eliza was close to four and in an extremely hyperactive stage of the disease. But she sang and talked with us. She'd play dress up and clopped around the house in my high heels. She rode her tricycle everywhere. She looked so healthy. But what was going on inside her body and brain was a much different picture. Meeting Izzy put us face to face with Eliza's future, the concrete and cruel reality of what this disease would do. A medicine didn't come in time for Izzy. She suffered greatly and passed away just a few weeks before her fifteenth birthday. for decades we've known the cause of this disease we can precisely measure the levels of toxic biomarker to determine whether a treatment's working and now we have the science to treat it thanks to nih funding and support from nonprofit foundations including our own a promising gene therapy was developed and propelled towards clinical trial at nationwide children's hospital in ohio while we anxiously were awaiting news the trial would begin Back at home, we watched Eliza's sentences becoming shorter, her words less frequent. She became agitated and hardly slept. The disease was taking hold. Two years later, in May twenty sixteen, the clinical trial finally began. And Eliza, then six and a half, was so very lucky to be the first child to receive that gene therapy. It was her chance at a life different from Izzy's, a chance to grow up. Now at sixteen, it's clear the therapy changed her life. She surpassed average life runs on the beach, plays in the water, uses picture cards to tell us how she's feeling and what show she wants to watch on TV. She can feed herself and goes to school every day. These are simple but incredibly meaningful abilities that have a huge impact on her daily life. And children treated with higher doses earlier in life have even more remarkable outcomes like Caroline who's now ten she can read, play on a softball team, and learn to ski on her recent family vacation. But despite these breakthroughs and nearly ten years after the trial began, families outside the trial are still waiting for access. Why? Because last summer the drug was denied approval, not because of safety or how the children were benefiting but for questions about manufacturing. And while this is an important issue, FDA could have used its flexibility to continue reviewing the application while addressing questions in parallel. You see, early on, trial data confirmed the drug's mechanism was more than just plausible, it was biologically effective, showing significant reduction of toxic biomarker within just six months after treatment in all the children. Granting accelerated approval based on this biomarker would have brought treatment access to children years earlier, preventing further brain damage and changing the lives of so many children, like Sadie who is here today, who is still waiting. The same drug application was recently resubmitted, but FDA issued another denial, for yet more paperwork before agreeing to review it again. Congress has given FDA the tools of flexibility it needs to accelerate approvals for these devastating diseases but sadly flexibility and speed are not actually what most rare disease patients are witnessing. Transformative therapies are at FDA's doorstep and so with great respect families are pleading for FDA to unlock the door and move with urgency so that our children can have a chance at the life they deserve. Thank you.

Thank you for your testimony and thank you uh, Mister Campbell, for your testimony. Now we'll go to questions, Senator Johnson.

Thank you, Mister Chairman, and and again, I have to commend you for another excellent hearing here. Um At the start of the hearing I I received a text from Laura McGlynn, who uh reminds me that ten years to this day, as Chairman of Homeland Security, I held a hearing Titled, " Connecting Patients to New and Potential Life-Saving Treatments". Her her son Jordan, who suffered from Duchenne muscular dystrophy, testified at that hearing, was was certainly present there. Uh, two years later that resulted in Right to Try, which was not easy to pass. I had to hold up the FDA user fee bill. Uh, had to water down Right to Try quite a bit to make sure that big pharma wouldn't sabotage it. Uh, they did sabotage it over in the house, but President Trump's leadership, he forced the house to pass the Senate version. It's it's main benefit is its name. It's very limited in its application, unfortunately. But people have the right to try. Laura has also begged me, begged me in a text to mention Adalurin and Duramyosel, two two investigatory drugs, that is are also being held up by the FDA for Duchenne muscular dystrophy. Um. I think we probably are going to need another piece of legislation, probably right to try two point O, something that's gonna be far more effective than the current right to try. But I'll tell you, reading this testimony this morning, you can maybe tell just by my passion, it enraged me. It enraged me. that these families, these patients are being denied effective treatments because the regulatory roadblocks. Quick story, and again, I I I wanna ask questions, but a quick story. After I met the Duchenne muscular dystrophy community, they went up before a panel of FDA. This was probably in two thousand sixteen, seventeen or eighteen, begging, there were about sixty Duchenne muscular Patients' families begging the FDA, please approve this investigatory drug for our children. Again, time is muscle, time is brain. And that panel, I don't know who sat on it, listened to those sixty families begging them. And said no. Just like they said no, and I can't even pronounce these these diseases and drugs. They say no time and time and time again. That has to change. Congress is directing the FDA, be more flexible, say yes. You know, these patients understand the risks. They ought to have the right to try. Doctor Schmauman, am I pronouncing that right?

Yes, sir.

I don't want you throwing anybody under the bus because I don't want just to impact future approvals. But describe your meetings with cedar. And it to me it's shocking to have one of those members of that panel say, " Why should we listen to you?" "Well, because you're a doctor at Harvard, you're treating patients, you're having success, you're giving them a new lease on life, and you've got bureaucrats inside these agencies saying, Why the hell should we listen to you? So I want you going into greater de- describe what those meetings are like.

Thank you, Senator. We've heard a few a few words a few times. Heartbreaking is the experience of patients and families going through this, and the compassion that is required. I saw none of that in the three meetings with the FDA. The members of the panel were uh like talking to a brick wall. There was no engagement. no dialogue, in fact they said as much, this is not a dialogue, this is not a collaboration. Uh, they're, they did not seem to uh see the suffering of the patients, and they didn't hear the science. They were rigid and inflexible and unyielding. Um, the uh, FDA worked with the company uh initially, but then they changed their mind later. And so as the d- the uh studies unfolded, everything came to a grinding halt. This drug in particular, is safe, it metabolizes into a drug that's been there for thirty years, in the market, and is safe. Patients say it works. The doctors say it works. The study shows it works. The double-blind first lie first study showed it worked. The real-world evidence shows it works. Patients behind me, maybe one of them, talking to them yesterday, say it works. This drug works. What, to paraphrase, what is their problem? And my experience of the people on that panel, three times, as a private citizen coming for the first time to the FDA was deeply distressing.

So I've already texted Doctor Tracy Beth Hoag, told her I've read your testimony, I'll be sending her your testimony. I hope she's listens to this. And if I if I could just take couple more minutes. Doctor O'Neill, you are obviously personally impacted by this. Can you describe any meetings you've had? To, you know, similar to to what we just heard. So so again, the American people understand what these regulators are doing and not doing doctor O'neill

thank you um you know i i will say that my interactions with um regulators have been um kind so so maybe a bit of a different perspective is they they have listened they have been interested to hear what we had to say, to hear the patient perspective, and I I think where we're challenged is that we don't see that translated into regulatory action. And some of the decisions that are coming out are not benefiting patients, uh, right now. So so,

Yeah.

listening is great, but two-way conversation and collaboration is actually what's needed, and greater transparency in how patient experience data and patient input is actually being integrated into these decisions.

So so my guess is that panel f- with Shand Musker, just re-back in twenty seventeen, whatever, probably listened very nicely to the families, but they still said, no, that's an unacceptable answer. Again, I, you have my commitment, I'm going to delve into this, we we're gonna right these wrongs. But thank, Mister Chairman, this is again an excellent hearing, uh, we've gotta follow up on this, this is just completely unacceptable. Thank you.

Thank you, Senator Johnson. Uh, Senator Also-Brooks.

Thank you so much, Chair Scott, also Ranking Member Gillibrand. Uh, and I'm so grateful to be here today, uh, joined by so many patient advocates, caregivers, family members. Uh, I've heard from many Marylanders living with rare diseases and from their families, including dozens who have visited my office, uh, this week to share their priorities and their concerns. As I underscore with the NIH Director, a few weeks ago, patients suffering from devastating diseases do not have time to wait for needless delays to critical cures. For Marylanders with rare diseases, delayed access is not just an inconvenience, it is a matter of life or death. For many with rare conditions, clinical trials are their last and best hope. These patients also depend on a regulatory process that is science-driven, and capable of turning research into real treatment. Instead of strengthening those foundations, this administration is constantly disrupting clinical trials, slowing innovation, and undermining the pipeline to cures. Scientific integrity should always guide decision making, and we must protect the fire wall between the Food and Drug Administration and political influence. President Trump and Secretary Kennedy continue to decimate critical parts of that system. The instability they've caused ripples across families, physicians, researchers, and innovators, and patients pay the price. So, Miss Kennedy, I'd like to ask, over the past two weeks we saw a striking example of political interference at the FDA involving a seasonal MRNA flu vaccine from Moderna. The agency first declined even to review the application, then reversed course just one week later after revised regulatory approach. The abrupt change raised serious concerns about transparency, predictability, and political influence in what should be a scientific process, an episode many have described as regulatory whiplash. What does that kind of volatility signal about how the FDA is functioning right now, and why does that matter for rare disease reviews that depend on regulatory consistency?

So First of all, thank you so much, Senator, for being here and for all of you being here today and for this important issue. I think first, it's important to say that I'm not an expert in vaccines and we're I am here really to focus on rare disease, but I appreciate the question really asking about the trends that we're seeing and us being here really trying to follow the trends and understand what that means for rare disease. Um, I also agree with Doctor O'Neill that we have seen real intention from career staff and staff scientists at fda around their engagement but what we're concerned about is to your question what seems to be reversals in decisions where there had been previous agreement previous work with sponsors that was um directing um sponsors to move in one direction and then regulatory decisions seem to be yielding different decisions at this point So as I stated in my testimony, we have seen recently twenty-three complete response letters issued in rare diseases that are delaying access to the patient community and having devastating consequences to our community. Many of those actually are decisions that are reversals in regulatory agreements that have been made previously. Additionally, we're very concerned that previously, if there were to be a complex decision that needed to be worked through between a sponsor and the agency, an advisory committee would have been convened. And we have seen sixty five percent fewer advisory committees convened in twenty twenty five than twenty twenty four, and in fact none since July. So we're very concerned that the regulatory tools that are at the disposal of the agency to really work through some of these really complex decisions aren't being utilized.

Thank you. And just very quickly, if I can also go to Miss O'Neill, finding new cures doesn't happen overnight, and it rarely happens in a single year. Breakthrough therapies are built over decades of careful scientific work and discoveries and NIH-funded laboratories form the foundation for treatments that later move into clinical trials through regulatory review, and ultimately into patient care. So when NIH research capacity is disrupted, as we have seen, and weakened, How does that set back the search for new cures long before therapies ever reach the FDA?

Thank you for your, thank you for your question. Um, the NIH is a critical source of funding for uh innovation in this country, in scientific innovation. Um, it's interesting that, that when there were um disruptions and uncertainty in the funding, we received a a flood of requests about funding from our small um non-profit foundation. And I think non-profit foundations across the country, we're seeing that and, you know, we're not equipped to take up all of the the the preclinical and transformative science that NIH can do. So the role of the NIH in supporting innovation is huge.

Thank you.

Thank you, Senator. Senator McCormick.

Thank you, Mister Chairman, and thanks to you and the ranking member for uh convening this and thank you all so much for being here today uh to help bring some of these uh critical issues to Americans and Pennsylvanians to light um Miss Kenny more than thirty million Americans live with rare diseases yet fewer than five percent have an approved treatment since uh as you mentioned since uh early twenty twenty five the FDA has issued at least twenty three complete response letters for rare disease therapies, while advisory committee's uh use has declined uh dramatically. So when late stage rare disease applications raise concerns, what alternatives to issuing a complete response letter should the FDA use, including advisory committees or structured post-approval commitments, to revolve to resolve issues without restarting the entire process?

thank you we appreciate that question so fda has it at has it at its disposal thanks to congress many types of engagements between sponsors and the agency um many of those have been made possible thanks to the user fees and we're concerned that many of those meetings and meeting types aren't occurring and that the crls are being utilized as a way to perhaps maybe even clear the docket or create delays. There could be a lot of reasons why that might be happening, but there are meeting types that have been implemented that could enable engagement to answer questions that sponsors and the agency might have. Um, we saw actually the agency deploy this during the um pandemic, the COVID pandemic, where we saw real rapid real-time resolution to um a crisis in our country. and the agency was able to interact with sponsors, get questions answered in real time. And then we saw that CBER tried to operationalize that in other places and spaces. We would really, as a rare disease community, like to see that operationalized within rare disease, because we believe that our rare disease community has the urgency and unmet need that matches that of a pandemic, of a crisis.

Yeah.

We have individuals in this room who have very limited life expectancies. And if we don't address what's happening in rare disease with that same sense of urgency, they would not be here with us if we were to convene this hearing another year from now.

Thank you. Thank thank you for uh highlighting that urgency and I I think we feel it, and you're helping us to feel it, so thank you for that. Mister Campo, just on the on the uh on the issue of accelerating the process, I was uh, taken by the fact, in preparing for this, that some countries are moving much faster on, uh, rare disease therapies. The European Union's fast EU program caps multinational clinical trial authorization at seventy days, and Australia allows many trials to begin almost immediately after an ethics approval. So, what's going on here? Uh, why is the, what will happen if the United States fails to keep pace, and what policy changes should we consider in the Congress given what appears to be a much more streamlined approach in other places.

Thank you, Senator. I completely agree. I think, you know, the United States has been the beacon of biotechnology innovation for so many decades and it's part of why we have more therapies approved today for rare diseases than we did you know decades ago and I would acknowledge legislation like the Orphan Drug Act that led to that um but as we said in our testimony and many of the panelists here today We've now stopped keeping pace with innovation and I think one exact point, uh, which I raised in my testimony as well, is speed to clinical trials. And for me, on the one hand it is time for patients and taking weeks, seventy days would be a remarkable number. And I think Congress could work with the FDA to pass legislation to encourage, again, centralized IRBs, leveraging, uh, digital technology and artificial intelligence to help us do that, reducing regulatory requirements. Um, for sure those things could speed us into the clinic. The other piece I think which is sitting behind this is our national competitiveness and in some ways our national security. And when we think about Australia, we think about Europe, collaborative nations, et cetera. There are other nations out there that perhaps we see in a different way. And and from my perspective, whether you think of that as a security threat or whether you think of that as a threat to getting drugs to patients, in either case I think Congress can take a leadership role in helping the FDA to speed through that process.