On February 26, 2026, Cure Sanfilippo Foundation Chief Science Officer Cara O’Neill, MD, was among four expert witnesses testifying before the U.S. Senate Special Committee on Aging to explore how U.S. Food and Drug Administration processes and evolving standards unintentionally delay patient access to safe and effective therapies, particularly for individuals living with rare diseases.
Foundation’s O’Neill offers powerful and personal testimony
“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,” said O’Neill before the committee.
“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.”
During her testimony, O’Neill shared the story of three children with Sanfilippo Syndrome, all diagnosed with the same deadly form of childhood dementia, but with very different outcomes:
Izzy was 11 years old when we first met, shortly after our daughter, Eliza, was diagnosed
with the same disease, Sanfilippo syndrome (MPS III). Izzy could no longer walk independently and had lost the ability to speak years earlier. She could no longer eat or drink by mouth without choking, requiring tube feedings for her nutrition. She suffered from seizures and movement disorders that twisted her arms and legs into painful positions.
Sanfilippo syndrome is caused by single-gene mutations that result in the accumulation of toxic levels of heparan sulfate, leading to progressive and irreversible brain damage.
During one of our visits, Izzy’s mother shared that she had come to accept that the disease would take her daughter’s life. But what she said next has always stuck with me:
“I fear her suffering more than I fear her death.”
At that time, my daughter Eliza was around four years old and in the extremely hyperactive stage of the disease. But she still sang and talked with us. She played dress-up and clopped around the house in my high heels. She rode her tricycle everywhere. She looked healthy, but we knew that the disease was continuing to damage her developing mind and body.
Meeting Isabel put us face-to-face with Eliza’s future: the concrete and cruel reality that lay ahead if she could not receive a treatment.
For Izzy, a treatment didn’t come in time. Heartbreakingly, she did suffer a great deal before passing away just weeks before her 15th birthday.
We know exactly what causes the disease. We can precisely measure the levels of the toxic biomarker (heparan sulfate) to determine whether a treatment is working. And now, we have ways to treat it.
Thanks to NIH funding and support from non-profit foundations, including our own, a promising gene therapy was developed and propelled towards a clinical trial at Nationwide Children’s Hospital in Ohio. Parents like us anxiously awaited news of the trial opening.
During this time, we noticed that Eliza’s sentences were becoming shorter and her words were becoming less frequent. She was becoming more agitated and hardly slept. The disease was taking hold.
In May 2016, the trial finally began. Eliza, by then six-and-a-half years old, was able to receive the gene therapy at the first starting dose. We felt so lucky that she would have a chance at a future different from Izzy’s; a chance to grow older and be healthy.
Now, at age 16, it’s clear that the treatment changed Eliza’s life. Surpassing average life expectancy, she can run on the beach and play in the water. She uses picture cards to tell us how she’s feeling, and what show she wants to watch on TV. She can use a fork to feed herself and goes to school every day. Simple, but incredibly-meaningful abilities that have a positive impact on her everyday life.
Children, like Caroline, who were treated at an even earlier age and with a higher dose, have demonstrated even more remarkable outcomes. Now, at 10 years old, Caroline can read books, is on a softball team, has playdates with her friends, and even learned to ski on her family’s vacation last week!
An entirely different future is in store for the few children who were able access treatment in the clinical trial. But despite these breakthroughs, and nearly a decade since the trial first began, children outside of the trial are still waiting for access – all while continuing to suffer more brain damage, month by month.
Last summer, patients’ hopes were dashed when the drug was denied approval – not for safety issues or concerns about how the children were responding to the treatment, but because of questions about the manufacturing process. While an important issue, a flexible regulatory approach could have allowed the application review to proceed while addressing any outstanding questions in parallel.
Data early in the trial confirmed that the drug’s mechanism was not just plausible; it is undeniably biologically effective. The levels of toxic biomarker (heparan sulfate) dropped significantly just six months after treatment in all the children. Earlier use of Accelerated Approval based on the scientifically-sound biomarker would have changed the lives of so many children.
“It’s death by a thousand technicalities”
Fellow witnesses Annie Kennedy of EveryLife Foundation for Rare Diseases, Dr. Jeremy Schmahmann, MD, of Massachusetts General Hospital Ataxia Center, and Bradley Campbell of Amicus Therapeutics also provided powerful insights.
“This is a policy of death by technicality,” said Schmahmann. “These little tiny glitches that that the FDA is producing land up not approving drugs and patients die as a consequence.”
“While we are heartened by recent announcements of therapy development initiatives such as the Rare Disease and 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 misaligned with these recent public pledges to expand the use of regulatory flexibility,” said Kennedy. “Since the start of 2025, we have seen at least 23 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.”
The rare disease community stands together, urgently asking for regulatory flexibility
In attendance at the hearing were Sadie Haywood (age 9) and her mom Ashley and aunt and Foundation Board Member Jessica Haywood.
Additionally, fellow rare disease advocates Kim Stephens, Mark Dant, Sharon King, and many others were also present for the hearing. Some held photos of their loved ones with rare diseases, for whom they were advocating.
Read the testimonies and watch a recording of the hearings.
Media amplifies hearing’s calls for change within FDA practices
- “Pressure builds as back-and-forth between uniQure and FDA intensifies,” Fierce Biotech, March 5, 2026
- “FDA Cruelly Holding Up Approval of Treatments for Rare Diseases, Despite Children Likely to Die Soon,” Townhall, March 2, 2026
- “Bipartisan frustration with FDA at Senate hearing,” Politico, February 27, 2027
- “‘Like talking to a brick wall’: Senate hearing takes aim at FDA’s rare disease review process,” Fierce Biotech, February 26, 2026
- “Senate hearing stirs concerns over FDA’s handling of rare disease drugs,” EndPoints, February 26, 2026
- “FDA’s handling of rare disease therapies criticized in Senate hearing,” Regulatory Affairs Professionals Society, February 26, 2026