Early 2025 brought a wave of optimism for those involved in rare diseases. The FDA’s new leadership had pledged to improve transparency and expedite approval processes, which many saw as a step toward getting urgent care to those in need.
But by summer, those hopes had dimmed. Despite robust safety data and significant patient benefits in clinical trials, the FDA issued a complete response letter that blocked the approval of a gene therapy from Ultragenyx (UX111) for patients facing terminal illnesses. This decision came after nine years of comprehensive data demonstrating its effectiveness for individuals suffering from Sanfilippo syndrome, a severe neurodegenerative condition.
Families dealing with harsh diseases—like Duchenne muscular dystrophy or aggressive cancers—are left wondering what the future holds.
In light of this, a coalition of patient advocacy groups wrote to FDA Commissioner Dr. Martin McCurry, urging him and other agency leaders to prioritize advancements for promising treatments in both Sanfilippo and other syndromes like Bath and Hunter syndrome.
In fields dealing with rare diseases and late-stage cancer, delays can be incredibly damaging, potentially stalling critical advancements in transformative therapies. Even if pharmaceutical companies manage to weather these delays, many patients may face irreversible deterioration or death because treatments aren’t available when needed.
These delays impact real families. Our daughter, Eliza, was diagnosed with Sanfilippo syndrome at just three and a half. While awaiting entry into the early phase of the UX111 trial, she expressed herself through writing, singing, coloring, and sometimes just lost her voice entirely, leaving us anxious through long nights.
Watching her neurological decline has been heart-wrenching. The decline is rapid initially, and yet parents face a slow, painful journey of watching their child lose even the simplest skills. The demands become overwhelming, too. Every day without treatment leads to more brain damage.
In 2016, when Eliza was six, she finally received the UX111. After her first dose, she slept through the night in her own bed for the first time. Now, not only does she surpass the average lifespan of those with Sanfilippo A (which is around 15 years), but she has also regained some communication skills, enjoys trampoline parks, and can use forks—an achievement for a condition where many rely on feeding tubes.
Another child who started UX111 at two shows even more remarkable progress. She’s now reading, playing softball, and hanging out with friends. In reflecting on the eight years since receiving gene therapy, her mother notes that she “lives a rich and happy life.”
As a pediatrician and researcher, I genuinely value the FDA’s role in safeguarding treatment effectiveness and safety. Yet it’s crucial for regulatory agencies to incorporate patient experiences in evaluating disease-specific risks and benefits, especially when considering drug approvals.
Research from the Cure Sanfilippo Foundation highlights that families affected by rare diseases are often willing to accept higher risks for potential treatments of devastating conditions. In the case of Sanfilippo syndrome, parents seek the ability to collaborate with their child’s doctors to make informed decisions about risks and benefits, but a lack of drug approval doesn’t limit their choices. They understand that without intervention, this syndrome leads to suffering and premature loss.
Currently, a staggering 95% of the 30 million Americans living with rare diseases lack approved treatments. Half of those affected are children, with 30% not making it past the age of five.
We simply need to do better.
It has taken tremendous efforts from Congress members, patients, families, doctors, and researchers. Recently, the FDA partially revived considerations for Duchenne gene therapy and re-evaluated Stealth’s Barth syndrome treatment using an accelerated approach. These are promising steps that should become standard.
The FDA must maintain its commitment to safety while balancing it with the urgent needs of patients and the relentless advance of serious rare conditions. Action is essential to ensure that more life-saving therapies are approved before patients who desperately need them are left behind.
Cara O’Neill, MD, FAAP, founded the Cure Sanfilippo Foundation after her daughter was diagnosed with Sanfilippo syndrome in 2013. The Foundation is an active member of the Rare Diseases Association.
