▶ 0:19:53Chair Scott: Good morning. The U.S. special senate committee on aging will come to order. We are here to ask a simple but important question, is the fta doing everything congress intended to do to quickly get safe, effective treatments to patients with rare diseases who cannot afford to wait. For more than 30 million americans living with a rare disease, making everyday sacrifices is a part of life, but something that they cannot forget to give up his time.
▶ 0:20:18Chair Scott: Time means the ability to walk, independence, being able to speak, eat, or even recognize a loved one. Often it's exactly what patients lose as therapy sits in regulatory limbo. Growing up, I saw firsthand how disease can affect a family. My brother had a rare hip disease and my family had no health insurance. My mother had to drive 200 route -- 200 miles round-trip to get the care we needed.
▶ 0:20:45Chair Scott: My brother could not afford to sacrifice time. Congress has been clear on an overwhelmingly bipartisan basis. We have given the fda flexibility to move faster for patients with serious and life-threatening conditions. In 2016, congress passed the 21st century cures act. That bill and other bills gave direction to the fda to encourage the use of real-world evidence, highlighting rare disease development requires adaptability and urgency.
▶ 0:21:16Chair Scott: The laws were meant to help cut through bureaucratic delays and give patients access to the care they need desperately. Here we are 10 years later, hearing from patients, physicians, and drug developers that the system is not working as intended. I've heard from the commissioner that he is working hard to fix the long-standing problems that the fda and I want to thank him for the work that he's done to make a strain system work better for patients.
▶ 0:21:44Chair Scott: However, advocates today will describe inconsistent review practices, shifting standards, and redundant and often late appearing data requests that in many cases may not be driven by safety concerns, but by an overly cautious and rigid approach that puts the bureaucratic process ahead of patients. As we will hear, the human costs to this regulatory slow walking is real. Many of those affected by these delays have no other treatment options. Patients from every state come to talk to our offices.
▶ 0:22:15Chair Scott: I'm sure it's the same with the ranking member, with irreversible declines in health happening while they and someone they care about wait for a treatment that may never come. It is heartbreaking to hear from families who are watching loved ones deteriorate were seen promising therapies get stuck in review. Meanwhile, small biotech companies struggle to survive years of uncertainty even when the science is sound.
▶ 0:22:41Chair Scott: There are serious national security consequences that come with the inaction and the delays . Our adversaries have accelerated their drug development approval. Fda and action here at home creates an economic and competitive issue. Let me be clear, the hearing is not about weakening state -- safety standards. Safety must always come first. But safety and speed are not mutually exclusive. A system can protect patients while acting with urgency, transparency, and common sense.
▶ 0:23:11Chair Scott: Some of you may be asking why the senate agency committee -- agent committee is tackling this while so many of those with rare diseases are young. Here is why. Part of this is making sure that more americans are given the opportunity to grow old. It may sound cliché, but we are all aging and of something stands 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.
▶ 0:23:38Chair Scott: It is my hope that today's hearing will be a useful tool in helping us understand what we can do to bring efficiency and transparency to the process. We are joined by an incredible panel of witnesses here today. All working towards a better future for people living with rare diseases. We have a lot of members in the crowd who are here because rare disease drugs are very important to them, I want to thank everyone for being here.
▶ 0:24:05Chair Scott: I would now like to recognize ranking member gillibrand for her opening statement.
▶ 0:24:09Sen. Gillibrand: Thank you for calling today's hearing, thank you to our witnesses and advocates who here for rare disease day on the hill. It makes a big difference that you come together to make sure that your loved ones are being heard and that this -- the challenges and struggles that you go through are being understood by lawmakers.
▶ 0:24:31Sen. Gillibrand: Everyone of us in this room today knows that when we have a friend or a loved one or a family member who has a rare disease, the most important thing is finding a cure, getting the treatment, and making sure that they survive. A disease is considered rare if it affects fewer than 200,000 people. But rare diseases are not actually that rare. One out of 10 americans is living with a rare disease.
▶ 0:25:00Sen. Gillibrand: 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 of the fda to evaluate them, congress has provided the agency with significant regulatory flexibility to encourage both biotech innovation and rare disease therapies.
▶ 0:25:27Sen. Gillibrand: These include the authorizing of the accelerated approval pathway to speed up the drug review, establishing programs like the rare disease endpoint advancement pilot to bolster novel endpoint development, and strengthening and expanding the use of patient experience data and real-world evidence in drug reviews.
▶ 0:25:49Sen. Gillibrand: These mechanisms are designed to help improve access to novel treatments for our patients and are supposed to provide drug sponsors with a permit -- protectable 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 is not working how it should be.
▶ 0:26:18Sen. Gillibrand: The fda approach to transparency and flexibility varies wildly between offices, divisions, and centers. We have seen a pattern of hesitation to use authorized flexibilities, limited communication with drug sponsors, failure to incorporate patient experience and real-world evidence reviews, and the fda shifting the regulatory position on trial design at the last minute, rejecting drug
▶ 0:26:48Sen. Gillibrand: Applications and requiring new clinical trial is that the sponsor may be unable to perform . This is heartbreaking for patients and it is why we cannot afford disruptions a treatment. Rare diseases can progress rapidly, causing irreversible harm, and in some cases premature death. This is frustrating for drug sponsors who face increased costs and delayed timelines that impact the viability of the clinical trials, particularly in the united states.
▶ 0:27:19Sen. Gillibrand: Uncertainty shaves behavior across the biotech ecosystem. Without consistency and protect ability, 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 is bad for patients. If we want the U.S. to remain the global leader in biotech and want american patients to have access to these novel treatments, things need to change.
▶ 0:27:47Sen. Gillibrand: Congress must hold the fda accountable. We must make sure fda fixes there inconsistent and unpredictable application of regulatory flexibility. It is essential for supporting innovation while upholding the highest standard for safety and efficacy in the approval of these rare disease drugs. Fda appears to be moving in the right direction.
▶ 0:28:12Sen. Gillibrand: With the rare disease evidence principles, the rare disease innovation hub proposing new pathways for approval, and trying to hire more reviewers. But it doesn't matter what agency leadership puts in a press release. It is about execution and implementation across all levels of the agency, consistency from top to bottom.
▶ 0:28:37Sen. Gillibrand: Congress will make sure 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 working with this committee to hold the fda accountable, because rare disease patients cannot wait.
▶ 0:28:57Chair Scott: Thank you, ranking member. I would like to welcome our witnesses, experts here to talk about how serious the issue is in the steps we can take to make sure that these patients are not left behind by regulatory delay. First I would like to recognize annie kennedy, chief mission officer at the everylife for rare diseases, a recognized leader in policy patient advocacy works directly with patients, caregivers, and families navigating the drug
▶ 0:29:27Chair Scott: Development and approval process . Everylife represents the voices of rare disease communities acrossr the country, asr they have long advocated for regulatory flexibility and timely access to life-saving therapy. Thank you for being here. Please begin your testimony.
▶ 0:29:44Ms. Kennedy: Thank you, chairman, for convening this critical hearing. I'm annie kennedy, chief mission officer for the everylife foundation for rare diseases and I'm honored to be here alongside the hundreds of advocates who joined us for rare disease week on capitol hill. Collectively we represent 30 million americans living with rare diseases. Today there are more than 10,000 rare diseases, 70% of which started in childhood.
▶ 0:30:16Ms. Kennedy: Facing progressive diseases, time is a commodity. Traditional placebo-controlled trials are often neither feasible or ethical when considering the challenges of the rare disease. Given the orphan drug act of 1983, your leadership provided tools that rocketed the U.S. into the most competitive developer of rare disease products. Each landmark law since has reshaped our landscape. In fact tomorrow marks the anniversary of another watershed moment for our community here on capitol hill.
▶ 0:30:48Ms. Kennedy: The md care act hearing convened in this same hearing room, presided over by senator arlen specter, included a 13-year-old named benjamin. 25 years ago I watched with great pride as he asked congress for actions that could help to cure him and his friends so that he could achieve his dreams of growing up, having a girlfriend, and serving his country. Congress responded.
▶ 0:31:15Ms. Kennedy: In that time, congress built a framework that incentivized rare product development, authorized regulatory flexibility, created new pathways for approval, and embedded patient experience into review. Fewer than 5% of rare diseases currently have fda approved treatments, or teen hundred orphan designated therapies are changing the lives of patients and families. But recently this momentum has shifted.
▶ 0:31:41Ms. Kennedy: We are here today because our community has experienced worrisome trends with devastating consequences. We are heartened by recent announcements of therapy development initiatives like the rare disease evidence principles for plausible mechanisms on the pathway and are eager to work with the agency on implementation, our rare disease community has experienced a series of product applications that seem to have been misaligned with recent public pledges to expand the use of flexibility.
▶ 0:32:09Ms. Kennedy: Since the start of 2025, we have seen at least 23 complete response letters declining to approve rare disease therapies, many of them under accelerated approval suggesting a hesitation to apply regulatory flexibility through surrogate endpoints, natural history studies, and external controls.
▶ 0:32:30Ms. Kennedy: At the same time, advisory committee meetings for drugs and biologics combined -- declined by 65% compared to 2024 opportunities for external opportunity expertise on rare product decisions. We asked families who had been personally affected by these recent decisions to reflect on their impact. These stories will be shared for the record.
▶ 0:32:56Ms. Kennedy: Story after story spoke to chilling consequences of recent regulatory delight -- delays in clinical trial hurdles, as one mother shared about her son, "he is now receiving an experiment of treatment and is thriving. For the first time since his diagnosis, his doctors told us that with his treatment, a near normal life is within reach. A disease that had once come with a teenage expiration date, we are now living in fear.
▶ 0:33:24Ms. Kennedy: Not because science failed, not because company started -- stop fighting rare diseases, but because of regulatory inconsistency. We are here today because congressional action is needed to make sure that this generation of patients will benefit from our existing rare disease treatment pipelines.
▶ 0:33:40Ms. Kennedy: We ask that congress engage fda to clarify their approach to approval for these diseases with consistent application of regulatory flexibility, urging the resumption of his--advisory committee meetings so that it performs complex reviews, urging congress to resource for rare disease innovation hub to strengthen cross center coordination and establish the rare disease condition advisory committee with a science focused development initiative.
▶ 0:34:10Ms. Kennedy: In closing, 25 years ago I stood in this room filled with rare families and today advances in science have put life altering treatments in reach of many, but they were not in time for those in the room with me 25 years ago. While ben achieved many of his dreams, he died two days before receiving his masters degree. We now have the opportunity to make sure this generation of rare disease patients will benefit from today's therapy development pipelines.
▶ 0:34:41Ms. Kennedy: Each time a promising therapy faces delays or demise, investment into future scientific promises unfulfilled and lives are lost. Time is the most precious commodity for the rare disease community. As she wrote from her -- his hospital bedside, "we are closer than ever to rewriting the future of these diseases, don't let my generation become the next group of mothers standing at gray's sides instead of graduations." thank you.
▶ 0:35:11Chair Scott: Thank you. Thank you, miss kennedy. Now I would like to introduce Dr. jeremy schmahmann, founding director of the ataxia center at massachusetts general and principal investigator for the laboratory for nido unum -- neonatal anomalies.
▶ 0:35:35Chair Scott: Treating patients with progressive and neurodegenerative diseases. He has seen firsthand the consequences of delayed access to care and the irreversible loss that patients can experience while waiting for regulatory decisions. His testimony will ground the discussion in the real world clinical impact that these delays have. Thank you for being here. Please begin your testimony. Dr. o'neill chairman -- Dr.
▶ 0:36:12Schmahmann: Chairman, thank you for the remarkable opening statements. I am the fogelman chair in ataxia and cerebellum neurology and professor of neurology at harvard medical school. I started the first center of this kind in the country and have treated these patients for 45 years. I've been the principal investigator for the study and my comments today reflect my personal and professional opinion, not necessarily that of my employer.
▶ 0:36:42Schmahmann: Senators, please help us fix the fda. It had -- it has rejected safe drugs, such as a drug that improves the quality of life in slow progression in spinal attacks. My patient, steve, for example, develop the ataxia, type three, in his late 30's. Like his mother before him, he will become increasingly disabled and will need to use a wheelchair, become bedridden and die young.
▶ 0:37:12Schmahmann: Since starting a year ago, he has not changed. Mary, in her late 40's, has type two. After 6.5 years, she has not changed. These inherited neurodegenerative diseases worsen inexorably this business saying the same is success. Like other rare diseases, ataxia is difficult to study, deteriorates slowly, and manifests differently within families.
▶ 0:37:42Schmahmann: There are 15,000 of these patients in america, some of which affect hundreds, some just a few. Congress has recognized these challenges and passed legislation mandating that fda use regulatory flex ability and real-world evidence on rare diseases like ataxia. The drug that was used to treat als for 50 years was reported to improve it.
▶ 0:38:06Schmahmann: Based on this in the plausible mechanism of action, bio haven developed a new drug that metabolized but was taken once per day with better vein -- brain penetration and fewer side effects. Early in the drug development, patients are stopped treatment after a year of open therapy insisted that they go back on because they told us that the condition worsened after stopping the drug.
▶ 0:38:33Schmahmann: So, bio haven, to their credit, provided it to their patients and ran a one year of double-blind placebo-controlled study. Patients with type three improved compared to the placebo , falling less with fewer injuries. Bio haven requested approval of it for the ataxia type three based on these results. The fda refused to review the new drug application.
▶ 0:39:00Schmahmann: Bio haven obtained fda feedback and used a revised protocol to follow patients on the drug for another three years, comparing them with patients in two natural history studies. In this real-world evidence study, the new drug showed significant improvement across nine prespecified fda and, slowing the disease by 50% to 70%, a dramatic result that was supported by patient and physician feedback.
▶ 0:39:27Schmahmann: We were all shocked when the fda denied approval of this safe drug that makes people better. I wrote six letters to the fda between 2023 and 2025, cosigned by 17 ataxia colleagues, asking the fda to review the application again and work with them to make the drug available if necessary, performing close market studies. I never heard back.
▶ 0:39:56Schmahmann: Now 300 patients, stable, will have to come off the drug, and they are distraught. I met three times with the fda center for drug evaluation and research. On each occasion, they did not heed the patients were the experts who are considering the science. One panel member said to me -- why should I listen to you?
▶ 0:40:21Schmahmann: The proposed path forward is another placebo-controlled trial that will take five years to eight years, or a randomized withdrawal approach from those patients benefiting from it. If this happens, plate -- patients on the placebo will die . I believe that this is unethical, lacking charity, mercy, or kindness. Senators, please, save our patient's lives.
▶ 0:40:47Schmahmann: Use your authority to require that the fda consider real-world evidence and apply the flexibility you have legislated, and in so doing restore transparency, integrity, and competence to the agency. Thank you.
▶ 0:41:02Chair Scott: I would now like to recognize ranking member gillibrand to introduce the next witnesses.
▶ 0:41:09Sen. Gillibrand: Thank you, Mr. chairman. I want to introduce our next witness, bradley campbell, president and ceo of amicus therapeutics, a biotechnology company focused on discovering and developing new medicines for people living with rare diseases.
▶ 0:41:28Sen. Gillibrand: During his tenure he led the global commercialization of a medication that was used to treat a disease in adults approved by the U.S. food and drug administration on an accelerated basis. He brings 20 years of experience in the rare and orphan disease fields. You may begin your testimony.
▶ 0:41:54Mr. Campbell: Thank you very much. It is my privilege to be here today to speak to you about our experience developing drugs for those living with rare diseases. I'm honored to be here with my fellow panelists. I feel less qualified than they are to speak today, but I hope I can share some perspectives on the challenges and opportunities that we have to fix the system.
▶ 0:42:16Mr. Campbell: I have had the privilege to work at amicus for 20 years and have dedicated most of my professional career to developing treatments for those working with rare diseases and I thought I could begin with a patient story that I think captures the spirit of the conversation we are having. At a recent patient meeting we asked -- discussed patient experience data on making endpoints for clinical trials more meaningful for patients.
▶ 0:42:40Mr. Campbell: During the break a young woman with pompeii disease took me aside and said that what would be most meaningful for her is if she could breathe on her own for just one minute. It would make the difference between her life and her death. This is not an approvable endpoint and pompeii disease, of course, but she depends upon a mitten -- mechanical ventilator to breathe. If it fails, if the battery dies, the aide fails to clear the mucus, 60 seconds of her own breath could make the difference between life and death.
▶ 0:43:10Mr. Campbell: That comment is a powerful reminder as to why patients and caregivers must help us design better clinical studies with real endpoints that make a difference for them. We cannot ask patients to wait for years before approved treatments come when the difference between life and death can be a single breath.
▶ 0:43:29Mr. Campbell: I think that the rare disease innovation ecosystem in the united states has made enormous progress over the last 20 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 sheds light on how regulatory flexibility in working together can make a difference in drug development.
▶ 0:43:54Mr. Campbell: When we developed our new medicine for fabry disease, we learned in early studies that in some patients the drug worked, and some 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 that develop into the disease might best respond to the therapy and just as importantly, which may not.
▶ 0:44:20Mr. Campbell: The fda ultimately incorporated that into the label, improving the -- approving the first ever oral precision medicine for those living with the disease. What does that mean? When sponsors and regulators work together, the result was the oral treatment option that has saved thousands of patients, saved them years of biweekly infusions. We know that rare diseases are biologically complex and difficult to study.
▶ 0:44:48Mr. Campbell: Sitting here today, 95% of more than 10,000 known rare diseases lack fda approved treatment. These are statistics that many of us are familiar with. Fast forwarding that pace of development, it would take us 150 years to treat only half of the remaining rare diseases.
▶ 0:45:07Mr. Campbell: Small and midsized biotechnology companies like amicus, bio haven, and others, are the engine of rare disease innovation but can only succeed if the system adapts along with the medical needs. There are three practical areas that we can work together to improve that system. First, we must start clinical trials faster. We know that he and other countries they started weeks and not months.
▶ 0:45:34Mr. Campbell: We can reduce administrative requirements, leverage single ir ease, use digital tools to get into the clinic faster. We must also find better ways to measure efficacy, using biomarkers, innovative endpoints, accelerated approvals, things that the fda has now, but we must use them more, and we can make manufacturing inspection and rules work better. The single biggest delay often times is inspections from getting access to medicines.
▶ 0:46:05Mr. Campbell: The fda has tools like remote inspections that rely on global regulators to reduce that inefficiency. Let me close with a final story. At a patient meeting last year, a man with fabry disease told us that when he was diagnosed in his 30's, he stopped saving for retirement, he thought there was no reason he could live that long.
▶ 0:46:26Mr. Campbell: Fast forward 15 years, fabry disease is a treatable disease, advancements have changed the trajectory, and for the first time he is thinking about a future he thought he would never have. I look forward to working together with members of this committee and regulators in the broad community here that are focused on rare diseases to find ways to make sure we have a flexible, adaptable, agile regulatory system that can keep pace with modern innovation.
▶ 0:46:53Mr. Campbell: Thank you for the opportunity to testify as I look forward to taking your questions.
▶ 0:46:58Sen. Gillibrand: Thank you. I want to move to introduce our next witness, Dr. cara o'neill, chief science officer at the qr sanfilippo foundation -- cure sanfilippo foundation, empowering families with the resources they need to navigate their journey. Dr.
▶ 0:47:19Sen. Gillibrand: O'neill founded the foundation after receiving the diagnosis in 2013 for her daughter. At the foundation she leads patient focused research efforts and awareness working to bridge the gap between scientists, clinician, industry, and family, was awarded the international 2020 patient advocacy leader award by the world symposium for exceptional science. You may begin your testimony.
▶ 0:47:49Dr. O'Neill: Thank you. On behalf of 15 million children with rare diseases in this country, thank you truly for your concern. I am cara o'neill, chief science officer at the sanfilippo foundation, mother to eliza who has a ultra-rare disease called sanfilippo syndrome. One of many forms of childhood dementia leading to progressive and irreversible brain damage.
▶ 0:48:17Dr. O'Neill: I would like to first acknowledge the critical public service the fda and its staff, who shoulder complex and heavy workloads every day. We know that pressures are significant because we feel it, too. Of late we have seen many press releases highlighting new policies and programs that encourage us to look out into the future with hope.
▶ 0:48:42Dr. O'Neill: Today the committee has called us here with the recognition the current regulatory barriers are significantly impacting patients right now, never more starkly than for degenerative conditions where time is the most crucial factor in where every regulatory flexibility must be leveraged to meet this uniquely urgent need. We can see this illustrated in the story of the three girls with the same deadly disease but different lives.
▶ 0:49:09Dr. O'Neill: Isabel was the first child with sanfilippo my husband and I met after our own daughter receive the diagnosis. She was 11 and the disease had taken a tremendous toll. She could no longer walk independently, taking only a few steps if her mother held most of her weight. She 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 twisting her arms and legs into painful positions.
▶ 0:49:40Dr. O'Neill: During one visit, her mother shared that she had come to accept that the disease would take her daughter's life. What she said next always stuck with me, which was that 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.
▶ 0:50:03Dr. O'Neill: She sang, she talked with us, play dress-up and walked around in my heels, writing her tricycle everywhere, looking so healthy. What was going inside -- going on inside your body and brain was a much different picture. Meeting isabel put us face-to-face with alliances -- at's future. Is he passed away a few weeks -- isabel passed away a few weeks before her 15th birthday.
▶ 0:50:33Dr. O'Neill: For decades we have known the cause of the disease. We cannot precisely that we can precisely measure the toxic biomarker. 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 at nationwide children's in ohio.
▶ 0:50:56Dr. O'Neill: While we were anxiously awaiting the news that the trial would begin, at home we watched eliza's sentences become shorter, wordless frequent, becoming agitated, hardly sleeping. The disease was taking hold. Two years later in may of 2016 the clinical trial can and eliza, six and a half, was lucky to be the first child to receive that therapy. It was her chance at a life different from isabel's. Now at 16, it is clear that therapy changed her life.
▶ 0:51:28Dr. O'Neill: She surpassed average life expectancy, runs on the beach, plays in the water, uses picture cards to tell us how she is feeling end of the shows she wants to watch on television. She feeds herself and goes to school every day, simple but meaningful abilities that have a huge impact on her daily life. She it -- children treated with higher doses earlier in life have even more remarkable outcomes, like caroline, who is now 10, who can read, play on a softball team, and recently learned to ski.
▶ 0:51:59Dr. O'Neill: Despite these breakthroughs and 10 years after the trial began, families outside the trial are still waiting for access. Why? Last summer the drug was denied approval. Not because of safety and how the children were benefiting, but because of questions about manufacturing. While this is an important issue, fta could have used its flexibility to continue reviewing it while addressing the questions in parallel.
▶ 0:52:25Dr. O'Neill: Early on trial data confirmed that the mechanism was more than just plausible, it was biologically effective, showing significant reduction of the toxic biomarker after six months of treatment. Renting accelerated approval would have brought treatment access to children in years earlier, preventing further brand damage and changing the lives of so many children, like sadie, who is here today and still waiting.
▶ 0:52:51Dr. O'Neill: The same drug application was recently resubmitted but fda issued another denial, asking for more paperwork before agreeing to review it again. Congress has given fta the tools of flexibility that it needs to accelerate approvals for these devastating diseases. Sadly, flexibility and speed are not what most rare disease patients are missing. Transformative therapies are at the doorstep of the fda.
▶ 0:53:17Dr. O'Neill: With great respect, families are pleading for the fda -- fda to unlock the door to the life our children deserve. Thank you.
▶ 0:53:26Chair Scott: Thank you for your testimony. Thank you, for your testimony. Now testimony. >> Mr. chairman, I have to commend you for your excellent hearing.
▶ 0:53:48Chair Scott: Hearing from laura glenn, she reminds me that 10 years to this day, I held a hearing entitled connecting patients to new and potential life-saving treatments . For her son, jordan, who suffered from muscular dystrophy, she suffered -- she testified at the hearing in two years later it resulted in right to try, which was not easy to pass.
▶ 0:54:11Chair Scott: I had to hold up the fda user fee bill, water it down quite a bit to try and make sure that big pharma wouldn't sabotage it. They did sabotage over the house but because of the trump leadership you force the house to pass the senate version. It's, it's, it's main benefit is its name. It is very limited in application, unfortunately. But people have the right to try.
▶ 0:54:40Chair Scott: Laura has also back me, begged me to mention [indiscernible] , two investigatory drugs that are also being held up by the fda for muscular dystrophy. I think that we are probably going to need another piece of legislation, right to try 2.0, summing that will be far more effective than the current right to try.
▶ 0:55:08Chair Scott: But I will tell you that reading this testimony this morning, you can maybe tell by my passion, it in raged me. It enraged me. These families, these patients are being denied effective treatments because of the regulatory roadblocks.
▶ 0:55:33Chair Scott: Quick story, and again, I want to ask questions, but quick story, after I met with the duchenne muscular disk retreat community, they went up before a panel at the fda, probably 2016, 17, or a team, begging. There are about 16 of these families, they begged the fda to please approve this investigatory drug for our children. Again, time is muscle. Time is brain. That panel, I don't know who sat on it.
▶ 0:56:05Chair Scott: They listened to those 60 families, begging them, and they said no. Just like they said no, and I cannot even pronounce these diseases and drugs. They said no time and time and time again. That has to change. Congress is directing the fda to be more flexible. Say yes. You know, these patients understand the risks.
▶ 0:56:36Chair Scott: They ought to have the right to try. Dr. schmahmann, am I pronouncing that right?
▶ 0:56:43Dr. Schmahmann: Yes, sir.
▶ 0:56:46Senator: I don't want to keep throwing people under the bus just to impact future approvals. But describe your meetings with cedar. To me, it's shocking to have a member of that panel say -- why should we listen to you? Because you are a doctor at harvard? Treating patients? Having success? Giving them a new lease on life?
▶ 0:57:14Senator: You have got bureaucrats inside the agency saying -- why the hell should we listen to you? I want you going into greater detail to describe what the meetings are like. >> senator, we have heard a few words a few times. Heartbreaking is the experience of the families going through this. There is compassion required. I saw none of that in my three meetings with the fda. The members of the panel were, it was like talking to a brick wall.
▶ 0:57:45Senator: There was no engagement, no dialogue. In fact, they said as much. This is not a dialogue, not a collaboration. They did not seem to see the suffering of the patients and they did not hear the science. They were rigid, inflexible, unyielding. The fda worked with the company initially, but then they changed their mind later. As the study has unfolded, everything came to a grinding halt.
▶ 0:58:15Senator: This drug in particular is safe to metabolize into a drug that has been there for 30 years in the market, and it safe. Patients say it's worth -- say it works. The study shows it works. The double-blind study showed it worked. Real-world evidence showed it works. Patients behind me, they say it works. The drug works. What is the problem?
▶ 0:58:40Senator: My experience of the people on the panel three times, as a private citizen coming to the first time to the fda, it was deeply distressing. >> I've already texted the doctor, I read your testimony. I will send her your testimony. I hope that she listens to this. If I could get a couple more minutes, Dr. o'neil you were obviously personally impacted by this.
▶ 0:59:05Senator: Can you describe any meetings you had, similar to what we've heard? The american people need to understand what these regulators are doing and not doing. Dr. o'neill?
▶ 0:59:17Dr. O'Neill: Thank you. You know, I will say that my interactions with regulators have been kind. Maybe a bit of a different perspective. They have listened. They have been interested in hearing what we had to say and to hear the patient perspective.
▶ 0:59:43Dr. O'Neill: I think that where we are challenged is we don't see it translated into regulatory action. Some of the decisions coming out are not benefiting patients right now. Listening is great, but two way is what's needed along with greater transparency in how patients experience data and how patient input is actually being integrated into these decisions.
▶ 1:00:16Senator: He probably listened nicely to the families but they still said no. Unacceptable answer. You have my commitment that I will delve into this and we will right these wrongs. Mr. chairman, again, this is an excellent hearing, we have to follow up, this is unacceptable.
▶ 1:00:32Chair Scott: Thank you senator alsobrooks?
▶ 1:00:36Senator Alsobrooks: Thank you, chair, ranking member. I'm so grateful to be here today joined by so many patient advocates, caregivers, family members. I have heard from many marylanders living with rare diseases, from their families, including dozens who have visited my office this week to share their priorities and concerns.
▶ 1:01:00Senator Alsobrooks: As I underscore with the nih director a few weeks ago, those patients suffering from devastating diseases don't have time to wait for needless delays to critical cures. To the marylanders with delay busy -- with diseases, this delayed access is a matter of life and death. For many with rare conditions, clinical trials are there last and best hope.
▶ 1:01:23Senator Alsobrooks: These patients also depend on a regulatory process that is driven by science, and capable of turning research into real treatment. Instead of strengthening those foundations, this administration is constantly disrupting clinical trials, slowing innovation, and underline -- undermining the pipeline to cures. Scientific integrity should always guide decision-making and we must protect the firewall between the fda and political influence.
▶ 1:01:53Senator Alsobrooks: The president and secretary kennedy continue to decimate critical parts of that system. The instability they have caused ripples across families, physicians, researchers, innovators, and patients pay the price. Miss kennedy, over the past two weeks we saw a striking example of political interference at the fda involving the seasonal mrna flu vaccine from moderna.
▶ 1:02:19Senator Alsobrooks: The agency first declined it to even review the application and then reversed course a week later after a revised regulatory approach. The abrupt change raised serious concerns about transparency and political influence and what should be a scientific process, an episode that 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 review that depends on regulatory consistency?
▶ 1:02:53Ms. Kennedy: First of all, thank you so much, senator, and to all of you for being here today. And for this important issue. First, it's important to say that I'm not an expert in vaccines. I'm here really to focus on rare disease. I appreciate the question, really asking about the trends we are seeing, and us being here really trying to follow those trends and understand what it means for rare disease. I also agree with Dr.
▶ 1:03:19Ms. Kennedy: O'neill, we have seen real intention from career staff and staff scientist at fda around their engagement. But what we are concerned about is, to question, what seemed to be reversals in decisions where there had been previous agreement and work with sponsors that was directing sponsors to move in one direction, and then regulatory decisions that seemed
▶ 1:03:50Ms. Kennedy: To be yielding different decisions. As I stated in my testimony, recently we saw 23 complete response letters issued and rare diseases that are delaying access to the patient community and having devastating consequences to our community. Many of those are actually decisions that are reversals in regulatory frameworks that have been made previously.
▶ 1:04:17Ms. Kennedy: Additionally, we are very concerned that previously if there were to be a complex decision that needed to be worked through between a sponsor and the agency and the advisory committee, that would have been convened. We have seen 65 percent fewer advisory committees convened in 2025 than 2024. In fact, none since july.
▶ 1:04:40Ms. Kennedy: We are very concerned that the regulatory tools at the disposal of the agency to really work through some of these really complex decisions are not being utilized.
▶ 1:04:51Sen. Alsobrooks: Quickly if I could go to -- if I could go to miss o'neill, regulatory breakthroughs regularly happen overnight or even in a single year. They often happen in the funded laboratories that form the foundations for treatments that later move into clinical trials to regulatory review and ultimately into patient care.
▶ 1:05:14Sen. Alsobrooks: When nih research capacity is disrupted as we have seen, how does that set back the search for new cures long before therapies ever reach the fda?
▶ 1:05:24Dr. O'Neill: Thank you for your question. The nih is a critical source of funding for innovation in this country. Scientific innovation. It's interesting that when there were disruptions and uncertainty funding, we received a flood of requests about funding from our small nonprofit foundation.
▶ 1:05:55Dr. O'Neill: I think that the foundations across the country saw that. We were not equipped to take up all of the preclinical transformative science that nih can do. So, the role of the nih and supporting patients is huge.
▶ 1:06:10Dr. O'Neill: Thank you. -- Sen. alsobrooks: thank you.
▶ 1:06:15Chair Scott: Senator mccormick thank you for convening this and for being here today to help bring some of these critical issues to americans, to pennsylvanians, to light. Miss kennedy, 30 million americans live with rare diseases, but fewer than 5% have approved treatments.
▶ 1:06:37Chair Scott: Since, as you mentioned, since early 2025 the fda has issued at least 23 complete response letters on rare disease therapies while advisory use has declined dramatically. So, when late stage rare disease applications raise concerns, what alternatives to issuing a complete response letter to the fda use? Including advisory committees structured postapproval commitments to resolve issues without restarting the entire process?
▶ 1:07:11Ms. Kennedy: We appreciate the question. Fda has at its disposal thanks to congress many types of negotiations between sponsors and the agency. Many of those have been made possible thanks to user fees. We are concerned that many of those meetings of many types are not occurring and that the crl's are being utilized as a way to even clear of the docket or create delays.
▶ 1:07:39Ms. Kennedy: There could be a lot of reasons why that might be happening, but they are meeting types that have been implemented that could enable engagement to answer questions that sponsors and the agencies might have. We actually saw the agency deploy this during the pandemic, the covid pandemic, where we saw a real rapid real-time resolution to crisis in our country.
▶ 1:08:06Ms. Kennedy: The agency was able to interact with sponsors, get questions answered in real time. And then we saw that sieber tried to operationalize that in other places and spaces. As a rare disease community we would like to see that operationalized within rare disease, because we believe the rare disease community we have has an urgency and unmet need that matches that of a crisis.
▶ 1:08:35Ms. Kennedy: 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 the hearing in another year.
▶ 1:08:51Sen. Mccormick: Thank you. I think we do feel it and you are helping us to feel it. Thank you for that. Mr. campbell, just on the issue of accelerating the process, I was taken by the fact that in preparing for this, some countries are moving much faster on rare disease therapies. The european union fast program cap's multinational clinical trial at 70 days.
▶ 1:09:20Sen. Mccormick: In australia, they allow many trials to begin almost immediately after the ethics approval. So, what is going on here? What will happen if the U.S. 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?
▶ 1:09:43Mr. Campbell: I think that the united states has been the beacon of biotechnology innovation for decades. It's a part of why we have more therapies approved today for rare diseases then we did decades ago and I would acknowledge legislation like the orphan drug act that led to that. As we said today with many of these panelists, we have stopped keeping pace with innovation. One point that I raise my testimony is the speed to clinical trials.
▶ 1:10:13Mr. Campbell: For me, on the one hand it's time for patients. Taking weeks, 70 days, that could be a remarkable number and congress could work to pass that legislation with centralized irb's and artificial intelligence that helps us do that. Reducing regulatory requirements. For sure those things could speed us into the clinic. The other piece, which I think is sitting behind this, our national competitiveness and national security.
▶ 1:10:43Mr. Campbell: When you think about australia, think about europe, collaborative nations, etc., there are other nations out there that we see a different way and whether you think about them as a security threat or a threat of getting drugs to patients, we can take an important role in helping the fda to speed through the process.
▶ 1:11:04Sen. Mccormick: Thank you all for being here.
▶ 1:11:07Chair Scott: Senator kim?
▶ 1:11:11Senator Kim: A couple of words I heard that really just hit the nail on the head. I love, love your reactions to it. Talking about the different problems we are facing at the fda, the bureaucracy and workforce issues, the word that really hits home is urgency. I heard you use that word, miss kennedy. I feel that that is what we are really talking about here. A government moving at the speed of urgency of the parents trying to save a child.
▶ 1:11:43Senator Kim: We are struggling to understand what the actual purpose is and the speed at which we need to move. Look, I have two boys, eight and 10. I would do anything for them. It's like, how do we translate that into the urgency of a government trying to be responsive? I think that's where the disconnect hits on so many levels. I worked national security in afghanistan, iraq, other wear.
▶ 1:12:15Senator Kim: I saw this government move with the urgency when they thought that lives were on the line. But why is that we can't translate it into another circumstance where there are millions of lives on the line but people don't have time to wait? That's a purpose. How do we talk about this as a national security priority? The same reason we try to save lives abroad is the same reasons we do so at home.
▶ 1:12:45Senator Kim: Does that make sense, miss kennedy?
▶ 1:12:46Ms. Kennedy: Absolutely. Congress has recognized this urgency of the statute and has recognized the reflected accelerated approval pathway through the use of surrogate outcome measures and biomarkers in clinical trial design and rare disease.
▶ 1:13:08Ms. Kennedy: What we are concerned about is that in many of these letters what we see reflected is the fda, especially in one of the medical products, it seems to be a trend that we are detecting, backing away from comfort levels of use of surrogate biomarkers. What we have seen in rare disease is that surrogates work. Surrogate biomarkers save lives.
▶ 1:13:32Ms. Kennedy: We have more than 250 products that have been approved through the accelerated approval pathway. Fewer than 20% of those are for the noninfectious rare diseases, meaning that there is a distinction between what is happening in the rare disease community in this room and in the broader rare community.
▶ 1:13:55Ms. Kennedy: It's really important, looking at these statistics, that we look at the different medical product centers, what they are comfortable with doing. That is why we know that the tools are available and we want to ensure that they are being utilized.
▶ 1:14:10Sen. Kim: Mr. campbell, I want to bring you in on this because you talked about this at length, build up what we just heard. How would it expanded use of adaptive trial designs or surrogate endpoints by the fda lend itself to achieving better outcomes when it comes to rare disease approvals?
▶ 1:14:28Mr. Campbell: I think the first step is just use what we have available to us. If you look at oncology, I think 2024 there were 8000 different therapeutics in the conical trial design. I think a large part of that is welcoming use of accelerated approval and circuit biomarkers. Our own products was approved under surrogate biomarker. The competitor product was approved.
▶ 1:14:59Mr. Campbell: These things work. I get it, rare diseases are biologically complex. It is difficult understand how long it will take. You can't do randomized controlled studies in the same we can with broader disease populations. When it is done right, 10 years later after using real-world evidence in a registry, they were able to concert -- confirm and now it is a flipper product. For me the tools are there. As we discussed, it is consistency in using the tools that exist.
▶ 1:15:30Sen. Kim: Urgency on the trials and moving forward on the approvals but I also want to raise another issue which is just how long it often takes to build any fracturing facilities here in the united states. The level of slowed lists -- slowness. I with urgency on the manufacturing side as well. What can you be showing us about the decision-making manufactures are going through especially in terms of being able to build this and manufacture this year in america and here at home.
▶ 1:16:00Sen. Kim: Cameco by background and because we work with external manufacturers as a small-cap company, we don't have the capital to build our own manufacturing facilities and we certainly don't have an environment to be able to do that so we work outside of the united states. It takes three to five years just to build a state-of-the-art manufacturing facility for protein therapeutics. Another one to two years to get that facility inspected. You are talking five to seven years from we want to do this to when it actually has medicine coming off the line for the patients.
▶ 1:16:30Sen. Kim: In my mind, it is mutually beneficial to all of us so create incentives -- they don't have to be financial incentives. Help with permitting, with inspections, give priority to inspections or homegrown manufacturing facilities, create an environment supportive of bringing manufacturing home versus using, which is what we have seen the last couple of years, more sticks to try to prevent probably more qualified person to speak to this -- so
▶ 1:17:00Sen. Kim: Let's use incentives instead of six to encourage that. I think the united states ecosystem and patients all benefit from doing that.
▶ 1:17:05Sen. Kim: Mr. chair, we have talked at length in this committee about the benefits on so many levels of having manufacturing here in america, the speed with which we can move, capabilities. These are some very concrete things I hope we can follow up on and really come up with a game plan here. It honestly is pathetic we are not able to do this with a greater level given the skills and talent and resources of our country. We can't and should be doing better. Thank you for holding this hearing today.
▶ 1:17:35Chair Scott: Did you have more questions? >> the elephant in the room here is so we have the laws in place, maybe could be beefed up, it is a personnel issue, right? I fear not even necessarily the heads, possibly bureaucrats there for decades for whatever reason, they don't like a particular drug. They are able to sabotage it.
▶ 1:18:02Chair Scott: My question, how can you overcome inconsistency from one bureaucrat to the next bureaucrat, changing the ministrations, particular bureaucrat that is been there for decades that just keeps blocking things? How do you get to the personnel issue? I will start with you, Ms. kennedy.
▶ 1:18:22Ms. Kennedy: So I think my experience differs from some on this panel in that we have seen great examples of models where we have had public meetings and public workshops where fda has come together with the patient community which I think is incredibly important mechanism to have meetings, where we could have regulatory agreement around the use of certain innovative models and clinical trial design. Surrogate and endpoint.
▶ 1:18:52Ms. Kennedy: Natural history studies, control arm that have been allowed --.
▶ 1:19:00Sen. Johnson: I point out in a meeting like that, panel 50 to 60 families and they still said no.
▶ 1:19:09Ms. Kennedy: I love that reference but you may not know, probably don't know is part of being with the foundation, I was with -- they may have been as advisory.
▶ 1:19:21Sen. Johnson: Where you the meeting? Can it
▶ 1:19:26Ca Ms. Kennedy: The advisory did vote nope at the agency brought that internally and --
▶ 1:19:35Sen. Johnson: Overruled it.
▶ 1:19:37Ms. Kennedy: The agency still has the authority to make the decision because they heard from the community. What we are concerned about right now is the agency isn't engaging with the patient community.
▶ 1:19:50Sen. Johnson: Dr. o'neill, and your testimony you talked about the complete response letter, bureaucratic -- in other words, the "no" letter. You got the no letter not necessarily because of safety or lack of efficacy, but can you explain that?
▶ 1:20:14Sen. Johnson: It seems like a pretty weak excuse where you could fix the manufacturing process so this drug can be made available. Talk about that.
▶ 1:20:29Dr. O'Neill: I am not an expert on gene manufacturing, however, the sponsor was very transparent in reviewing the full crl with our community so we could understand truly what the concerns were.
▶ 1:20:44Dr. O'Neill: Many of them were noted to be things like a crack on the floor not in the manufacturing area or a tarp that was out back or things that really are unrelated to our children.
▶ 1:21:02Sen. Johnson: Trust me, I have been through audits. You can find an excuse to write something up, pretty flimsy excuses. That is my concern. Dr. schmahmann, in your case, it was based on real-world -- it seems like the real-world evidence was completely in favor of allowing patients access to this drug? Talk a little bit about why you got a clr from a no letter.
▶ 1:21:31Dr. Schmahmann: One of the thoughts that came to me as we go through this process of what happened with the crack in the floor in the factory is this is a policy of death by technicality. These tiny glitches the fda is producing end up not approving drugs and patients die as a consequence.
▶ 1:21:55Dr. Schmahmann: I am glad to hear their people in the fda for doing what congress requires them to do, but that speaks to the unpredictability and erratic nature of the responses and the performance of the people and the fda. There are many ways to go forward to use clinical trials and use the new technology to bring treatments to patients faster that are safe and make a difference. Science advances. Regulation is keeping up with the new advances.
▶ 1:22:26Dr. Schmahmann: Seems like the fda is having trouble with that. So the fda must keep pace with the updates in science using the biomarkers, serum or imaging, using digital markers, using patient reported outcomes. Understanding what patients are saying. The key issue here is the real experts are the patients. They are the experts by experience. They are our research collaborators.
▶ 1:22:55Dr. Schmahmann: Everyone of us has something pretty we are all patients. We are talking about us. Whether it is a rare disease or not. The approach that can be taken, including what started our institution a platform trial where you could have one small group of controlled in a number of other patient cohorts trying different drugs. And there are innovations both in the clinical trial design, biomarker space. This is where we need to move.
▶ 1:23:23Dr. Schmahmann: The urgency is exactly what you're saying, there is an urgency now -- some of the drugs on the table now, the ones you heard about from Dr. o'neill and myself, they should be approved this week. There's no reason not to. One forward, we need to find a way to expedite this and make it a better process and have a sense of when you're going to the fda, you know what you're getting. It is not just a random scatterplot of who is to get what kind of --
▶ 1:23:49Sen. Johnson: Is in a root cause literally the doctors? They been replaced by regulators? Doctors are the ones most knowledgeable in this equation and you are shunning off to the side -- what you're saying doesn't count because regulators have replaced you in terms of making these decisions for patients. Isn't that a big problem? Dr.
▶ 1:24:11Schmahmann: I saw on your wall the mission statement. The fda is not doing that. It is the opposite. Communication, dialogue, teamwork between the physicians, the patients, the pharma who make the drug, regulators -- that is a two-way street. It is a dialogue. In medicine when we do rounds in the morning on our patients in the hospital, there is a discussion.
▶ 1:24:39Schmahmann: The physicians and the residents and the nurses, physical therapists come the patient in the family. It is a conversation, discussion. This is not what we are hearing from across the board and certainly from the other rare diseases. It turns out 30 million people are behind us, as we said. Bringing to you the plea to make the fda what it was supposed to be, which is what you regulated it.
▶ 1:25:05Schmahmann: And allow us to work in a collaborative manner across the board were not with this hit or miss approach to who you're going to get on a committee. Looking for accountability and effective leadership of the fda, it is their responsibility to hold the feet to the fire of the people under their personal leadership not just to say good things but to actually make them happen and bring new drugs to the america population, including us, our patients, my patients that are safe and effective.
▶ 1:25:30Sen. Johnson: I think this is an excellent hearing. Both you and the ranking member you pretty much diagnose the problem. In your opening statements, laid out the problems. This is eminently fixable and we have to fix it. I am committed to working with you to do so. Thank you for this hearing.
▶ 1:25:46Chair Scott: Senator gillibrand.
▶ 1:25:49Sen. Gillibrand: In 1972, the federal does -- the revised rec to provide independent expert scientific input on product reviews and policy topics. In 2025, fda canceled any advisory committee meetings and indicated that it would like to move away from involving advisory committees in the review of drug applications. For each of the witnesses, you can start, Ms.
▶ 1:26:14Sen. Gillibrand: Kennedy, how important is it to the rare disease community for fda to restore the use of advisory committees?
▶ 1:26:23Ms. Kennedy: It is everything. Yesterday, we had one of our communities showcase in front of close to 800 members of the rare disease community how an advisory committee meeting helped inform a key regulatory decision by showing how an open public hearing enabled members
▶ 1:26:54Ms. Kennedy: Of that community illuminate the nuance of a very complex regulatory decision. In a very complicated regulatory review. As senator johnson just highlighted, I have been a part of many advisory committee meetings for communities, including the duchenne community. An advisory committees don't always vote yes. That is not the point.
▶ 1:27:21Ms. Kennedy: The point is for external experts, including clinicians, including those with statistical expertise, manufacturing expertise that are not always internal to the agency to be brought to bear on regulatory decisions because we realize with 10,000 rare disease, it is not possible for fda to always have all of that expertise internal.
▶ 1:27:44Ms. Kennedy: Those committee hearings must be at the veil of the agency, but also those public hearings must be available so patient communities who are participating in clinical trials can share what their experiences in this clinical trials are. One of the challenges we have in clinical trial design is we don't always know what we are going to find when clinical trial begins.
▶ 1:28:10Ms. Kennedy: We design a clinical trial hoping we are going to be able to select the best outcome measures. The sometimes patient communities who participate in those trials experience other benefits. And though syrians enable us to hear from -- those hearings enable us to hear from others so we couldn't make the best decisions possible for the patient community around safety and efficacy.
▶ 1:28:35Ms. Kennedy: Eliminating those hearings eliminates the chance for fda to make the decisions that are in the best interest of the patient community.
▶ 1:28:43Sen. Gillibrand: Dr. schmahmann, Dr. o'neill, congressional actions have advanced how patient experience data is included in the development and valuation of rare disease therapies. What is the importance of the patient voiced in this regulatory process and what more is needed to ensure fda includes this information in his decision-making?
▶ 1:29:03Dr. Schmahmann: I agree it is critical. There is a deeper problem -- if you don't listen to somebody else's advice on a complex story, that is the opposite of humility. It is a denial of the patient's humanity and it is sort of hubris. You don't want to hear what the patients have to say? Who are you? That is the problem. This is all about the patients.
▶ 1:29:32Dr. Schmahmann: To deny the patient voice in drug development -- I agree completely with Ms. kennedy, determine the endpoint when you start is fine if the disease is well known to one million's of people. But in our case, the first clinical trials in the 2016, we did not know what would change. We did take a guess. Devising the scale and trial.
▶ 1:30:01Dr. Schmahmann: The patients told us, I am not falling my speech is better. That was a different outcome we did not understand in the beginning. That is the epitome of regulatory flexibility. There is a role in medicine, listen to the patient. They are telling you the answer. The second piece is, ignore the patients at your peril.
▶ 1:30:22Dr. Schmahmann: What we have here is denying the patient's story is the peril not of us but of the patient because now the drugs are not been approved. I think you've hit the nail on the head here. If you are ignoring the patient, then why are you getting up in the morning and coming to do the work you do at the fda?
▶ 1:30:42Sen. Gillibrand: Well said. Dr. o'neill?
▶ 1:30:45Dr. O'Neill: Obviously, you have heard the patients are not outside of the drug developing process. They are critical to it. Advisory committees as any mention are an important place where we can have that scientific dialogue and hear from patients and their expanse is also science. It is human science.
▶ 1:31:11Dr. O'Neill: The interaction needs to come way before that because by the time we get to an advisory board, tens of millions of dollars have been spent, maybe a decade has gone by. We have not treated potentially that many patients who needed treatment. So having a true collaborative dialogue early in the process is essential and something -- an opportunity that needs to be acted upon within the fda.
▶ 1:31:42Dr. O'Neill: I think one other thing we our understanding is key and sites around risk tolerance. We also want safe medicines but we also want the opportunity to save our children. Because those answers about a clinical trial come way down the road. And as Mr.
▶ 1:31:58Dr. O'Neill: Campbell explained, real-world evidence, disease monitoring programs, this is where we need to be focusing on these innovative ways -- maybe not so innovative, honestly, anymore, but more frequently used and supported ways to provide that longer-term evidence to support accelerated approval.
▶ 1:32:23Sen. Gillibrand: Mr. campbell, do you want to add?
▶ 1:32:29Mr. Campbell: For sure. I think what we keep coming back, you hear the theme, have the tools in place, yet the advisory committees and accelerated approval pathways. I think frustration is when they are deployed inconsistently and without clarity from the sponsors and from the patient community, from the physicians in terms of how you end up meeting the expectation of it not come into a positive resolution. There's one other piece we haven't talked about if I could introduce that, the rare disease innovation hub.
▶ 1:32:59Mr. Campbell: We want to talk about things congress could proactively do, we have a jewel modeled after that was successful in oncology but my observation would be it is underfunded and probably are empowered to do what it needs to do.
▶ 1:33:13Mr. Campbell: What we think about the advisory committees and staffing at the fda, think about consistency between reviewers, hungers could directly fund the rare disease innovation hub in a meaningful way that would allow us to train experts I could sit across from review teams and bring some of that consistency, humanity, humility, expertise that perhaps each of the individual teams or new reviewer on the team does not quite have. Again, I think we have a lot of the tools we need, we just do who encourage the fda to use them in the right way.
▶ 1:33:45Mr. Campbell: That is one example we have not talked about were congress could fund that directly and allow the fda to make it a much more valuable tool.
▶ 1:33:50Sen. Gillibrand: Thank you.
▶ 1:33:52Chair Scott: When you hear the testimony, I think all of us internalize it. I have six grandsons and a granddaughter. Thank god everybody -- everybody's got problems, right? They don't have a rare disease that is going to shorten your life. I can't imagine what a family is going through and they have a family member that has something and they believe there's a possibility that something could change their life and it doesn't happen.
▶ 1:34:24Chair Scott: I would be pretty frustrated. I would be more than that. So, Mr. kennedy, it is important for people to come to congress and talk about their concerns with regard to the drug approval process?
▶ 1:34:44Ms. Kennedy: I know you're asking me but there are about 800 people on the hill that would be happy to answer that question as well. [laughter] throughout this time here this morning, starting with your opening remarks, we have cited many laws that have been transformational for the rare disease community.
▶ 1:35:05Ms. Kennedy: In every single one of them started with a member of the community meeting with their elected official and talking about a roadblock that could be transformed and turned into a resource and a tool. And every single one of those laws has transformed lives and ultimately has saved lives. So the answer to your question is an emphatic yes.
▶ 1:35:29Ms. Kennedy: We are so grateful for the time you take to be with our community, listen to our community, to engage and to become partners with all of us. So thank you.
▶ 1:35:38Chair Scott: Does the fda appreciate you guys coming here? [laughter]
▶ 1:35:44Ms. Kennedy: I think many do, yes. Maybe some know. I think overall over the years I have been in this space 30 years and I think we have had strong partnerships with the agency and many times the agency has very much appreciated our support.
▶ 1:36:01Chair Scott: Dr. schmahmann, from a clinical standpoint, what happens to patients with access to treatment is delayed due to the regulatory process rather than safety concerns?
▶ 1:36:13Dr. Schmahmann: They progressively deteriorate, loose function. They can't live their lives, go to work, spend time with her family, make a living, be productive citizens of society in that way. They become part of the family that people have to take care of instead of taking care of the family themselves. Then they become duke -- debilitated and they die young. Family members in our case see that. They see their future in the mirror.
▶ 1:36:43Dr. Schmahmann: There is a high instance of depression and suicidality in this community as well. This is across the spectrum. This is not a motor control problem alone. This is a social, emotional, societal issue. The issue about medications that improve neurological function in real-time work at the level of the physiology -- brain cells are sick before they die.
▶ 1:37:09Dr. Schmahmann: If you have a medication, even if it is not gene therapy, if you have a medication we know the mechanism and you stop the neurons being so hyperactive that they die, you actually are improving function and slowed the release over time so you're modifying these things. The absence of the medication that can treat the disease means each day that this drug and others like it are not being approved needs the patients are losing brain cells and are closer to death.
▶ 1:37:36Dr. Schmahmann: It is heartbreaking to see as you all set in the onset and we are hoping this can change from today.
▶ 1:37:40Chair Scott: I think in your testimony you said the fda suggests withdrawing patients from compassionate use care to evaluate whether the conditions would deteriorate. Despite physicians expressing the harm would be irreversible. Tell me about what are the ethical implications of that?
▶ 1:38:01Dr. Schmahmann: If you have a disease where there is a symptom like a migraine, for example, you can see advice -- if I talk to drug and you go back a medication you're ok.
▶ 1:38:14Dr. Schmahmann: In a neurodegenerative disease like these, if I'm being provocative, the last time we had a catastrophe in medical science in the U.S., 1922 in 1972 -- 1932, 1972 when people with syphilis were not treated so doctors could see what happened to them and that patients were not told, that is a case study for every person who is going and human studies
▶ 1:38:45Dr. Schmahmann: Research in the united states. We learn about that case. You cannot treat patients like guinea pigs. You have to have them on your story as part of the research collaborator experts by experience. If we have a drug, as we do here, that is virtually safe and you what patients to come off the drug so you can see if they worsen -- in other words, if your brain cells are dying under your care -- that is a poster child, tuskegee version two and it is entirely unacceptable. I reject it outright.
▶ 1:39:17Dr. Schmahmann: There should not have recommended that. Whoever did, I would suggest they take an updated education sessions on clinical trials and human studies research. It is not ok, senator.
▶ 1:39:29Chair Scott: I can't imagine doing that. Mr. campbell, talk about inconsistent fda standards, how it impacts timelines, costs. Is it easy to raise money if the fda is inconsistent? Does it make your job easier? Cameco no, is the candid answer -- Mr. campbell: know, is the candidates are.
▶ 1:39:53Chair Scott: We have created this rich ecosystem of innovation which has been supported by congress are supported by fda over the years, supported by modern technology. That brings in new companies that bring in new innovations and offer some therapies we have talked about here today that are now stuck in front of this regulatory process. Reality is, and this is in my written testimony, for many small midsized biotech companies, it takes decades to become profitable which means we are going hand in mouth begging dollars from investors.
▶ 1:40:22Chair Scott: If there was a clear path forward and to be confident of individual return, they will keep investing in the ecosystem keeps going and going. If we continue to create the uncertainty, create an around manufacturing timelines, approval timelines, changing the goalpost at the end, I'm confident those investor dollars will go somewhere else. I will tell you transparently, having gone to the recent j.p.
▶ 1:40:46Chair Scott: Morgan health care conference, I heard more opportunities about chinese therapeutics and companies than ever before. I don't think that is an accident. 10, 20 years ago we might have thought the science was a good, distrusted the quality and safety. I can tell you innovation and the science is equally as good as ours. We still have an advantage but if we are not careful, we will lose that and at the end of the day, the american patients suffers, the economy suffers.
▶ 1:41:16Chair Scott: I am concerned that is a real threat in addition to the most important piece, which is making sure drugs get to the patients faster.
▶ 1:41:22Chair Scott: Dr. o'neill, and progress of rare diseases, how should regulators account for the fact clinical decline is often irreversible? Should the harm of waiting the weight alongside uncertainty? If so, how?
▶ 1:41:35Dr. O'Neill: Thank you. To call back to Dr. schmahmann's points around this and about exposure to not being on drug, the risks of not treating this disease are known. These are not in question. We know these children will be permanently severely brain injured for the rest of their lives.
▶ 1:42:04Dr. O'Neill: And there are critical time sensitive neurodevelopmental windows in childhood when it is important to intervene to be able to receive the maximum benefit. There is a continuum of this. But earlier is always better. And what we are still hearing as recommended to sponsors is that observational or no treatment or placebo-controlled trials are being recommended for these pediatric conditions.
▶ 1:42:35Dr. O'Neill: This is very, very troubling when we know that they will become brain injured. We have also seen -- when the parents asked me about this, I have to kind of step back and think, oh, my goodness, I know what a perfect science experiment looks like. Yes, that is the perfect science experiment. But these are children. You cannot do good medicine in this you're putting the patient's first.
▶ 1:43:03Dr. O'Neill: And following the ethics of medicine. We have heard changes around the use of animals and clinical studies. Last april the fda published its roadmap to reducing animal testing and preclinical studies.
▶ 1:43:18Dr. O'Neill: It says "due to the limitations of animal testing as well as ethical concerns about animal testing, there been increased focus within the scientific community on new approach methodologies." we are concerned about the ethics of animal testing more than we are concerned about the ethics of allowing children to be brain injured in clinical trials. I think we all need a gut check on that.
▶ 1:43:43Chair Scott: Would in of you like to talk about what patients and caregivers give you when the alternative is no treatment at all?
▶ 1:43:57Dr. Schmahmann: I think it starts with safety. Nobody likes side effects. Patients want to know it is safe. Given that piece, if we can make a comment about safety, the degree to which the medication works or not is often I think something the patients are willing to take on. The concert we hear from the others about that and the other rare diseases.
▶ 1:44:25Dr. Schmahmann: In our space, knowing the medications we have available are safe and have been shown in other circumstances, patients are not just willing they are -- we are getting emails every day for people around the world, what trust you have I can use to try and slow down the process of my disease?
▶ 1:44:46Ms. Kennedy: I appreciate that question. My response would be for each subpopulation within each condition, within each targeted therapy that consideration would be very different. Which is why congress authorized the use of the benefit risk framework within the consideration of regulatory review. And that is one of the things we are concerned not being applied. We don't know how it is being used.
▶ 1:45:15Ms. Kennedy: One of the things we are asking for today is more questioning around how are these tools being utilized? Because every community for every clinical trial within every subpopulation of that community will approach that threshold for risk tolerance differently.
▶ 1:45:35Ms. Kennedy: And that is super important question, senator reid and we are just not sure that is being questioned the way it was intended for the teller station that is required for rear disease therapeutic development.
▶ 1:45:47Chair Scott: Mr. campbell, how important is transparency from the fda maintaining trust with rare disease communities? What happens when expeditions for delay or unclear or incomplete?
▶ 1:45:59Mr. Campbell: I feel like I sponsors manufacturers, we have a great duty to our patients and I think one of the senators asked why I am in this business. I will tell you, it is for the patients but we have a chance to develop a therapy for people with a rare disease, is sort of gets your blood. But you also bear great responsibility.
▶ 1:46:22Mr. Campbell: I think I feel like sponsors are at the front lines in front of the agency trying our best to get those drugs over the finish line. If we fail to do that for any reason, we owe it to the patients, community, caregivers to give them an explanation. When there is no good explanation or when it is a crack in the floor, that is just not good enough. I do believe sponsors bear some of that responsibility. I think it works best when we truly work together. If congress has the tools.
▶ 1:46:52Mr. Campbell: The fda has proven itself over time to be very effective in working with responses. Incredible, regulatory science, medical science that helped thousands of patients. But if you don't have that transparency and if you don't have that consistency, then we all lose. I really believe we are at the center of that. It pains me to hear the stories.
▶ 1:47:18Mr. Campbell: We are not in that position today, but we owe the responsibility to people who are giving a lecture to participate in clinical studies who have so much hope. We owe them clarity. We all do. Everybody involved in that, including the regulators.
▶ 1:47:32Chair Scott: Ranking member gillibrand, you have anything you want to add?
▶ 1:47:37Sen. Gillibrand: I would like the audience members who have pictures of their loved ones to stand, please, so we can see their loved ones. Thank you for coming to represent them. [applause]
▶ 1:48:01Sen. Gillibrand: Thank you all. I want to thank our guest in the corner who has been so well behaved this entire time. I am very proud of her. Being such a good girl. [applause]
▶ 1:48:16Sen. Gillibrand: I think you all for being here today. This has been an extremely powerful hearing. We have got some amazing testimony. I am very hopeful that we will find better solutions so we can all work together to get these cures our loved ones so desperately need. Thank you all. [applause]
▶ 1:48:35Chair Scott: So I want to thank everybody for being here and think the ranking member for this. We have been doing this for a little over a year and we have been able to do a lot of things together. What we heard today was not abstract policy theory. We heard from Mr. campbell that 95% of rare diseases still have no approved treatment. At the current pace it could take more than a century even close that gap. We heard from Dr.
▶ 1:49:00Chair Scott: Schmahmann about a multiyear data set supported by real-world evidence and natural history comparisons showing meaningful showing of disease progress certain. Still unable to clear the regulatory bar. Heard from Ms. kennedy that at least 23 rare disease therapies receive public response letters in the past year even as advisory committees meetings decline. Raising concern about whether the flexibility congress authorizes is being applied consistently.
▶ 1:49:27Chair Scott: Reminded that for some, success is not an abstract endpoint by the ability to hold one breath long enough to survive another moment. I recently spoke with commissioner mccarty who was clear the updates framework was built for, disease is not rare once. Limited reforms like a plausible mechanism pathway, greater flexibility for gene therapies, and strengthening the rear disease innovation hub. We look forward to working with him to ensure those changes are applied consistently and urgently for the patients.
▶ 1:49:55Chair Scott: And here to broken system and the fda cannot be fixed overnight. That said, he has made significant progress on -- and I'm encouraged by the reforms president trump has empowered commissioner mccarty to make. The fda and I know he cares about any results I make is the united states remains the world's reader for innovation and treatment rare diseases. Taking together the testimony presented before the committee, today ask one thing clear, the pressures that weather to predict safety is whether the system is moving with the urgency congress intended and patients require.
▶ 1:50:23Chair Scott: The committee will continue exercising oversight to ensure the flexibility enacted the law becomes reality and practice. I look forward to continuing to work with the members. If there any additional questions, the hearing record will be open until next wednesday 5:00 p.m. Thank you for being here. [captioning performed by the national captioning institute, which is responsible for its caption content and accuracy. Visit ncicap.org]