FDA approves one-time gene therapy for Sanfilippo syndrome

The O’Neills’ fundraising helped fund the first human trial, which began in May 2016

The Food and Drug Administration approved Fayuvi in September as a one-time infusion for Sanfilippo syndrome. The approval followed laboratory work dating to the late 1990s and a family campaign that helped fund the first human trial, which began in May 2016. Ultragenyx, which acquired the therapy’s rights in 2022, set the treatment’s price at nearly $4 million.

Eliza’s mother, Cara O’Neill, a pediatrician in Columbia, S.C., said her daughter always needed an accessory, such as a hat or scarf, when she was little. “She would always go get my high heels from the closet and clop around in those — which she scared us to death,” O’Neill said.

By the time Eliza turned 3, her parents noticed she was falling behind on developmental milestones. Eliza had learned many words but was not using them in a typical way in social situations, and was diagnosed with a pragmatic speech delay. In 2013, one of Cara’s colleagues suggested testing Eliza for a group of metabolic disorders to rule them out. The test found Sanfilippo syndrome. Cara O’Neill said she had learned about the rare inherited disease in medical school.

“When they said the word, it all kind of came rushing back,” Cara O’Neill said. “And that was just this bale of dread, like, oh, my goodness, this is horrific.”

Sanfilippo is a rare inherited disease caused by a faulty gene that prevents children from breaking down heparin sulfate, a molecule critical to normal cell function. As the substance accumulates in the body, it causes severe complications. Children with the disorder lose the ability to speak and walk, experience seizures and usually do not live past their teens, according to the Cure Sanfilippo Foundation, which the O’Neills started and continue to run.

Glenn O’Neill said it took him some time after learning Eliza’s test results for the diagnosis to sink in. “It wasn’t really until I got home that I realized how quickly the degeneration happened,” he said. “And that was really the point where we said, ‘Gosh. Whatever we need to do, we need to do it now.’”

At Nationwide Children’s Hospital in Columbus, Ohio, researcher Haiyan Fu had worked on a gene therapy in mice for Sanfilippo since the late 1990s. The approach used a modified virus to deliver a working copy of the broken gene to patients’ cells. Fu considered the experimental therapy promising.

“And if we treat early, it could be potentially a cure,” Fu said. “So I can’t give up.”

Keeping the research going and funded was difficult. Fu said she thought she would have to quit in 2009, but families of children with Sanfilippo prevented her from stopping. Fu said the families had helped from the beginning and did not want her work to stop. She recalled, “They said, ‘You can’t leave. Can we give you some of the funds for you to, you know, carry on?’”

In all, eight patient foundations, including Ben’s Dream and A Cure for Kirby, kept Fu’s work going until the research was ready for its first human trial.

A clinical trial would be expensive, and Glenn O’Neill had an idea for how to raise the money. “We reached out on a whim to some strangers that we found on the internet about making a viral video,” he said. Filmmaker Benjamin Von Wong made the “Saving Eliza” video over a few days in 2014.

In the spring of 2014, the video helped the O’Neills break GoFundMe’s record at the time, raising $1 million in a few weeks. The total soon reached $2 million. That money helped fund the first human trial, which began in May 2016.

The experiments were promising enough for the biotech industry to take notice. Ultragenyx acquired the gene therapy’s rights in 2022 and continued studying it. A few years later, the company submitted data to the FDA for review. The agency approved the therapy in September, and the one-time infusion received the name Fayuvi.

Ultragenyx CEO Emil Kakkis said the treatment works best in younger children because more brain function remains. “The treatment will work best the younger the child is because the more brain is remaining,” Kakkis said. “By the time they’re 2 or 3 or 4 years old diagnosed, getting figured out, they’ve lost a lot of ground.” He also said the company had treated a few children at six months old who had done well and that treating children very young produces better gene-therapy results.

Ultragenyx set Fayuvi’s price at nearly $4 million, tying it for the second-most-expensive gene therapy ever, according to 46brooklyn, a drug-price research firm. Kakkis said the company was committed to treating every patient regardless of price.

“There should be no logistical location, site or state or other kind of rule that stops us from getting the patient treated,” Kakkis said. “We understand what [we’ve] got to do.”

Moments after the FDA approval was announced, Fu received a call from Cara O’Neill and messages from other families that had funded her research. Some of those families had lost a child along the way. Fu said the approval was good news but brought mixed emotions: “It shouldn’t take this long.”

Eliza is almost 17 and was the first patient to receive the gene therapy during the 2016 clinical trial. Because she was 6 years old when treated, she had already lost the ability to speak, and it never returned. Eliza communicates with picture cards and devices, goes to school and, this summer, swam and learned to float on a pool noodle.

“I just feel proud of my girl. You know?” Glenn O’Neill said. “I feel proud of her. It’s been a rough road for her, but we also know she’s very lucky.”