FDA Approves the First Treatment for Sanfilippo Syndrome Type A, a Fatal Childhood Brain Disease ('Childhood Dementia'): a Single Intravenous Gene Therapy Halts Cognitive Decline

FDA Approves the First Treatment for Sanfilippo Syndrome Type A, a Fatal Childhood Brain Disease ('Childhood Dementia'): a Single Intravenous Gene Therapy Halts Cognitive Decline

On September 17, the FDA approved Fayuvi, the first therapy for Sanfilippo syndrome type A, an ultra-rare disease that strips children of cognition, speech, and movement and typically kills by age 15. Ultragenyx delivers a working copy of the broken gene in a single intravenous infusion. In the clinical trial, treated children gained cognitive skills at the ages when untreated peers were losing them.

In Sanfilippo syndrome type A, the SGSH gene is broken: cells cannot produce the enzyme sulfamidase, and heparan sulfate, which sulfamidase is supposed to break down, accumulates in the brain over years and destroys the nervous system. A child typically develops normally in the first years of life, then rapidly loses speech, memory, and the ability to walk. Until September 17, only symptomatic treatment existed.

Fayuvi delivers the SGSH gene using an AAV9 virus, which crosses the blood-brain barrier more effectively than similar vectors. This solves a problem that gene therapy could not crack for over a decade: getting a therapeutic gene into the brain through a simple intravenous drip rather than an injection into the skull. The same approach is being tested for related storage diseases: in cats with Sandhoff disease, a single AAV9 injection nearly tripled lifespan, even though that enzyme requires assembly from two genes rather than one.

"Achieving meaningful neurodevelopmental benefit through a single intravenous infusion is an important scientific milestone: it demonstrates that systemically administered AAV9 can deliver a gene to the central nervous system in quantities sufficient for a therapeutic effect in children"

That was the assessment of Megha Kaushal, acting deputy director of the relevant FDA division.

The evidence rests on eight years of follow-up in the Transpher A trial: 17 treated children scored 23.5 points higher on a cognitive development test than 27 untreated peers from the original control group (p<0.0001). Heparan sulfate levels in cerebrospinal fluid dropped across all age groups, confirming that the enzyme functions where it is needed.

The path to approval took more than a decade. The vector was developed at Nationwide Children's Hospital, and the rights went to the biotech company Abeona, which lacked the funding to complete registration. The asset passed to Ultragenyx in 2022, although the first participant had been treated as early as 2016. Approval did not come immediately for Ultragenyx either: in July 2025, the FDA rejected the application over manufacturing concerns rather than clinical data, and granted approval only 14 months after that refusal.

Fayuvi costs $3.95 million per patient, the second most expensive gene therapy after Lenmeldy at $4.25 million. The disease affects 3,000 to 5,000 people worldwide. Along with the approval, Ultragenyx received an FDA priority review voucher for a future drug, its second in a month; the voucher can be sold to another company for around $200 million. The treatment carries serious risks: 85% of children develop elevated liver enzymes and require an eight-week course of steroids, and integration of viral DNA into the genome is a long-term tumor risk.

"Before, parents given this diagnosis were told to take their child home and just love them. Now they will be given hope and a treatment plan"

said Cara O'Neill, chief scientific officer of the Cure Sanfilippo Foundation.

Fayuvi is Ultragenyx's second gene therapy approval in a month. In August, the company received approval at the same Bedford manufacturing facility for a therapy treating a different disease by delivering a gene to the liver. Now the same principle has proved effective for the brain: Sanfilippo syndrome has become another validation of the company's gene therapy platform.