The FDA cleared the first gene therapy for a disease that erases childhood

The U.S. Food and Drug Administration on September 17 approved Fayuvi, known chemically as rebisufligene etisparvovec-hopf, as the first treatment ever cleared for Sanfilippo syndrome type A, a genetic disease that progressively strips young children of the cognitive, language and motor abilities they had already learned. Until that Thursday, families had nothing but symptom management to offer a child diagnosed with the disorder, also called mucopolysaccharidosis type IIIA, or MPS IIIA.

“The approval of Fayuvi marks a historic moment for children and families living with MPS IIIA, which is a disease that has, until now, offered no approved treatment to alter its devastating course,” said Acting FDA Commissioner Kyle Diamantas. “Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A, and this milestone reflects the FDA’s commitment to action.”

A missing enzyme drives a fatal countdown

MPS IIIA is caused by a mutation in the SGSH gene that leaves cells unable to produce sulfamidase, an enzyme needed to break down a complex sugar molecule called heparan sulfate. Without it, heparan sulfate accumulates in cells throughout the body and progressively damages the brain and central nervous system, according to the FDA’s approval announcement. Children typically develop normally for their first year or two, then begin losing ground: speech regresses, behavior becomes erratic, mobility fails, and most do not survive adolescence. Ultragenyx Pharmaceutical, the therapy’s maker, estimates the disease affects roughly 3,000 to 5,000 patients in commercially accessible countries, with a median life expectancy of about 15 years.

Karim Mikhail, director of the FDA’s Center for Biologics Evaluation and Research, framed the approval against that backdrop of parents watching a diagnosis arrive with no way to slow it. “For families living with Sanfilippo syndrome type A, the trajectory of this disease is heartbreaking — children who develop normally in their earliest years facing a relentless regression with no approved treatment to slow it,” Mikhail said. “Parents and clinicians have been waiting far too long for an option.”

One infusion carries a corrected gene into the brain

Fayuvi works by loading a functional copy of the SGSH gene into a modified, non-infectious adeno-associated virus known as AAV9, then delivering it through a single intravenous infusion. Once inside a patient’s cells, the virus enables production of sulfamidase, letting the body break down the heparan sulfate that would otherwise keep accumulating. It is a one-time treatment rather than an ongoing therapy: patients receive corticosteroids beginning the day before infusion and continuing for at least eight weeks afterward to manage the immune response, and clinicians monitor for liver enzyme elevations, decreased platelet counts and a rare vascular complication called thrombotic microangiopathy in the weeks that follow.

The drug’s path to approval was not smooth. The FDA rejected an earlier application in July 2025 over manufacturing issues at Ultragenyx’s production facility and a third-party manufacturer, a setback that forced the company to rework its supply chain before resubmitting. Ultragenyx has said Fayuvi is now produced entirely in the United States, at its own gene therapy plant in Bedford, Massachusetts, and at Andelyn Biosciences in Columbus, Ohio.

Cognitive scores diverged from an untreated disease course

The approval rested on data from the Transpher A clinical program and its long-term follow-up study, which compared treated children against an external natural history cohort of untreated patients rather than a placebo arm — a design choice tied to the rarity and severity of the disease, according to a NeurologyLive review of the clinical record. Among 17 children who were under age 2 or in an earlier stage of the disease when treated, Fayuvi produced a 23.2-point higher mean score on the Bayley-III cognitive scale compared with the natural history group, measured between 24 and 60 months of age. Eight of those children reached a 36-month cognitive developmental age; no child in the untreated comparison group ever did.

A separate group of ten older or more advanced patients, treated later in their disease course, showed retention of function past the point where natural history data predicts decline. At their most recent assessments, all ten had retained verbal or nonverbal communication, nine of ten remained able to walk independently, and nine of ten could still feed themselves orally or independently — outcomes that diverge sharply from the rapid regression typically seen in untreated MPS IIIA by age three.

The price and the fight behind it

Ultragenyx priced Fayuvi at a wholesale acquisition cost of $3.95 million, chief commercial officer Erik Harris confirmed on a call the day of approval, according to Fierce Pharma’s reporting on the launch. That places it among the most expensive drugs ever brought to market, trailing only Orchard Therapeutics’ Lenmeldy, a gene therapy for metachromatic leukodystrophy priced at $4.25 million, according to a BioSpace analysis of the approval. Ultragenyx also received a priority review voucher, a transferable credit that can be sold to other drugmakers and that analysts have valued at roughly $200 million on the open market.

Ultragenyx chief executive Emil Kakkis said the company’s focus now shifts to getting the therapy to families quickly, with commercial shipments expected to reach qualified treatment centers within 30 to 60 days. Glenn O’Neill, co-founder of the Cure Sanfilippo Foundation, and Terri Klein, president of the National MPS Society, issued a joint statement calling the approval the product of “decades of advocacy, fundraising, collaboration, and perseverance across the Sanfilippo community,” and said they were celebrating “by honoring every family who contributed and remembering the children we lost while waiting for this day.”

Kevin Flanigan, director of the Center for Gene Therapy at Nationwide Children’s Hospital and the study’s principal investigator, traced the therapy back further still. The viral vector at the heart of Fayuvi, he said, “was first developed at Nationwide Children’s more than a decade ago,” passing through Abeona Therapeutics before Ultragenyx licensed it and carried it to a finish line few expected a rare-disease asset of its kind to reach.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

More from Morning Overview