FDA Approves First Gene Therapy for Pediatric MPS IIIA

Key Takeaways

• For U.S. children with Sanfilippo syndrome type A, Fayuvi is the first FDA-approved treatment.
• Fayuvi-treated children maintained or improved cognitive function compared with untreated historical controls.
• The FDA identifies thrombotic microangiopathy as a risk and tumor development from genome integration as a potential long-term risk.

Children with mucopolysaccharidosis type IIIA (MPS IIIA), also called Sanfilippo syndrome type A, progressively lose cognitive, language, and other developmental abilities as the condition damages the brain and nervous system. Their care previously focused on managing symptoms rather than changing the disease course. They had no approved treatment directed at the underlying disorder.

Fayuvi (rebisufligene etisparvovec-hopf) became the first treatment approved by the U.S. Food and Drug Administration (FDA) for pediatric MPS IIIA, as detailed in the FDA approval for pediatric Sanfilippo syndrome type A. Given as a one-time intravenous infusion, the therapy uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a functioning SGSH gene into cells. This enables production of sulfamidase, the enzyme deficient in MPS IIIA.

Effectiveness was assessed in an open-label, single-arm, multicenter study of children with MPS IIIA. Mean changes in cognitive scores were measured at ages 2–5 years and compared with an untreated historical cohort. This assessment window does not restrict the broader approved pediatric indication. Safety was assessed among pediatric recipients of a single intravenous infusion across clinical studies.

According to the FDA, treated children maintained or improved cognitive function relative to untreated historical controls, against an expected natural course of plateau and decline. Adverse reactions reported in more than 5% of patients included increased aspartate aminotransferase (AST), nausea and vomiting, fever, decreased appetite, reduced white blood cell and platelet counts, and increased amylase. The announcement did not specify individual incidence rates for these reactions.

The cognitive comparison relied on historical untreated controls rather than randomized concurrent controls, and the FDA did not provide a numerical cognitive effect estimate. Thrombotic microangiopathy is an identified risk. Integration of delivered genetic material into the genome, with possible tumor development, is a potential long-term risk, not a reported tumor event. The FDA states that all patients receive corticosteroid treatment beginning one day before infusion and continuing for a minimum of eight weeks afterward.

The approval provides a disease-directed option for pediatric MPS IIIA. The reported cognitive finding rests on historical controls, alongside identified and potential safety risks.

Clinician Questions

How does Fayuvi's SGSH gene delivery affect heparan sulfate in Sanfilippo syndrome type A?

In pediatric Sanfilippo syndrome type A, Fayuvi's AAV9-delivered functioning SGSH gene allows cells to produce sulfamidase, which breaks down heparan sulfate in lysosomes.

What kind of facility is used for Fayuvi infusion in pediatric Sanfilippo syndrome type A?

Fayuvi is infused in a healthcare setting equipped to manage infusion reactions in pediatric Sanfilippo syndrome type A.

Which regulatory designations did Fayuvi receive for pediatric Sanfilippo syndrome type A?

Fayuvi received Orphan Drug, Fast Track, and Breakthrough Therapy designations for pediatric Sanfilippo syndrome type A; the FDA granted approval to Ultragenyx Pharmaceutical, Inc.