Children's Wisconsin has been named one of just 20 hospitals nationwide, and one of only four in the Midwest, cleared to administer Fayuvi, the first-ever FDA-approved treatment for Sanfilippo Type A, a rare and ultimately fatal genetic disorder that damages children's brains over time. The one-time gene therapy received FDA approval days before the hospital's announcement, but Children's Wisconsin had not yet begun offering it to patients.
Sanfilippo Type A causes children's bodies to be unable to break down certain sugar molecules, leading to a buildup that damages the brain over time, according to FOX6 News Milwaukee. The condition is classified as a lysosomal storage disorder, sometimes described as childhood dementia, and it affects an estimated 1 in 70,000 live births, with Type A representing the most severe of four known subtypes, according to Medical News Today. Without a disease-modifying treatment, children with classic Sanfilippo Type A face rapid neurodegenerative decline, a median life expectancy of around 15 years, and a high risk of fatal respiratory infections, according to a study published on PMC that found pneumonia accounted for more than half of deaths among Type A patients.
For Roger Benda, an Illinois father, the approval landed just months after his 4-year-old son Ozzie was diagnosed with the disorder in March. “There is no cure. There is no treatment. Now we have a treatment,” Benda said, according to the FOX6 report, describing both the sadness and grief that followed his son's diagnosis and the hope the new therapy has given him.
How the One-Time Infusion Works
Fayuvi, known generically as rebisufligene etisparvovec-hopf, uses an adeno-associated virus serotype 9 vector to deliver a functional copy of the human SGSH gene through a single intravenous infusion, according to Drug Discovery News. The therapy is designed to let the AAV9 vector cross the blood-brain barrier and deliver the gene to cells, which then begin producing sulfamidase, the enzyme these children's bodies cannot make on their own, in order to break down the toxic buildup causing the damage. It's not a cure, but it's built to preserve neurologic function that would otherwise continue to decline.
The therapy developer, California-based Ultragenyx Pharmaceutical, worked from foundational research that began at the Jerry R. Mendell Center for Gene Therapy at Nationwide Children's Hospital's Abigail Wexner Research Institute, which spent years developing the underlying vector technology before the therapy reached clinical trials, per a release from Nationwide Children's Hospital. In the pivotal Transpher A clinical trial, young children who received the treatment scored an average of 23.5 points higher on the Bayley-III cognitive scale between ages 2 and 5 compared with an untreated natural-history control group, according to CheckRare.
A Narrow Window Before It's Too Late
The FDA's official prescribing label restricts Fayuvi to pediatric patients who still have preserved neurodevelopmental function, according to Sano Genetics, since brain degeneration in the disease is irreversible and the therapy cannot restore abilities a child has already lost. That makes early diagnosis critical, but it's frequently delayed because initial symptoms like speech delays, hyperactivity, and sleep disturbances closely resemble autism spectrum disorder or ADHD, according to the Cleveland Clinic. Children with Sanfilippo often appear healthy at birth, with symptoms not emerging until roughly ages 2 to 4.
At Children's Wisconsin, Dr. Michael Finkel said the hospital previously had no treatment specifically available for Sanfilippo Type A, calling Fayuvi's arrival a shift that can alter the entire natural history of the disease, according to FOX6's reporting. Patients receiving the infusion must begin systemic corticosteroid treatment one day beforehand and continue taking corticosteroids for at least eight weeks afterward to mitigate immune responses and infusion reactions, according to PharmExec.
Insurance Talks and a Wait of Several Months
The Benda family is now discussing Fayuvi treatment with its insurance company, and Ozzie may not receive approval for several months, per the FOX6 report. Roger Benda said he remains hopeful that the treatment will slow his son's decline even as the family navigates that process.
Upon granting the standard full approval, the FDA also awarded Ultragenyx a Rare Pediatric Disease Priority Review Voucher, an incentive designed to encourage pharmaceutical development for rare childhood diseases, according to a statement from Ultragenyx. Such vouchers can be used to expedite the FDA review of future drug applications or sold to other drugmakers, adding an economic incentive layered atop the medical breakthrough for families like the Bendas who are now racing against their children's own biology.
