The first few months of 2025 brought hope to the rare disease community. Food and Drug Administration leadership promised transparency and increased use of the accelerated approval pathway to deliver timely treatments to those in urgent need.
However, those hopes have been dimmed this summer as the agency has issued Complete Response Letters blocking approval of drugs for patients with terminal diseases, even when good safety data exists and patients in trials are showing meaningful benefit. This was the case with Ultragenyx’s gene therapy (UX111), which has nine years of robust data showing safety and benefit for those suffering from the fatal neurodegenerative disease Sanfilippo syndrome Type A.
It’s left those suffering from diseases like Duchenne muscular dystrophy, advanced cancers, and Sanfilippo syndrome wondering what’s next.
That’s why, in a letter delivered earlier this month, a coalition of patient advocacy organizations supported by more than 43,000 signatories called on FDA Commissioner Dr. Martin Makary and agency leaders to prioritize the advancement of promising therapies for Sanfilippo syndrome, Barth, and Hunter syndrome.
In the world of rare illnesses and late-stage cancers, any unnecessary delay can harm patients and cast aside future development of transformative therapies because the company may no longer have enough financing to wade through protracted regulatory timelines. And even when drug companies are able to weather the delays, many patients will have irreversibly deteriorated or died because an approved treatment was not available in time.
Drug development delays affect real families. Our daughter, Eliza, was diagnosed with Sanfilippo syndrome at three and a half years old. While waiting for the chance to enroll in an early phase of a trial of the drug UX111, she went from speaking in sentences, singing, and coloring to loss of speech with increasingly uncontrollable screaming and crying spells, sometimes lasting all night.
Helplessly watching this neurological deterioration in your child is devastating. Although the initial mental decline is fast, parents must cope with the progressive loss of their child’s most basic abilities, with ever-increasing demands on their time and energy. Each day without treatment causes more brain injury.
In 2016, at 6 years old, Eliza got her chance. She was the first to receive UX111, and afterward began sleeping through the night in her own bed for the first time. Today, she’s not only outliving the average life expectancy for Sanfilippo A (15 years) but also regaining non-verbal communication skills, jumping on trampolines at the bounce park, and using a fork to eat at an age at which most patients require a g-tube for nutrition.
Another child who received a higher dose of UX111 treatment at 2 years old is showing even more dramatic benefit. Now 10, she is reading, plays on a softball team, and hangs out with her friends. Reflecting on the eight years since gene therapy, her mom says, “It’s given my daughter a rich and happy life.”
As a pediatrician and researcher, I deeply value the FDA’s critical work in ensuring that treatments are safe and effective. However, it is essential that the agency integrate patient perspectives on disease specific risk-benefit profiles into its decision-making throughout the regulatory pathway, especially during consideration of drug approvals.
Published research from organizations like Cure Sanfilippo Foundation demonstrates that rare-disease families are willing to accept higher risks and uncertainty when it comes to treatments for devastating conditions. In Sanfilippo syndrome, parents want the autonomy to make individual risk-benefit decisions with their child’s doctor and not have their options limited by lack of drug approvals. They know that without treatment, Sanfilippo syndrome will lead to suffering and an early death for their child.
Ninety-five percent of the 30 million Americans affected by rare disease have no approved treatments. Half are children and 30 percent of them will die before age 5.
We have to do better than this.
It has taken extraordinary efforts from Members of Congress, patients, families, doctors, and scientists to draw attention to the need for more speed and flexibility around such diseases. FDA leadership has since partially reinstated a Duchenne gene therapy and offered accelerated reconsideration of Stealth’s Barth syndrome treatment. These are positive early signs that should become the norm, not the exception.
The FDA must now ensure that its commitment to safety and efficacy is balanced with the urgency of patient need and the relentless progression of serious rare diseases. Action is needed now — before more life-saving therapies, and the patients who need them, fall through the cracks.
Cara O’Neill, MD, FAAP, is the Chief Science Officer of Cure Sanfilippo Foundation, which she co-founded after her daughter was diagnosed with Sanfilippo syndrome in 2013. The Foundation is a signatory of the rare disease coalition letter.
