FDA Approves Rebisufligene Etisparvovec as First Gene Therapy for Children With Sanfilippo Syndrome Type A

The FDA has approved rebisufligene etisparvovec-hopf (Fayuvi; Ultragenyx Pharmaceutical), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. The approval introduces the first disease-modifying option for children with this rare, inherited neurodegenerative disorder.¹

Previously, treatment for MPS IIIA centered on symptom management and supportive care. Fayuvi is administered as a one-time intravenous (IV) infusion and is intended to address the underlying enzyme deficiency responsible for disease progression.¹

Gene Therapy Targets the Underlying Enzyme Deficiency

MPS IIIA is a lysosomal storage disorder caused by pathogenic variants in the SGSH gene. These variants result in deficient activity of sulfamidase, an enzyme needed to break down heparan sulfate. Progressive accumulation of heparan sulfate in cells, including cells within the central nervous system, contributes to cognitive decline, behavioral changes, speech loss, motor impairment, and other manifestations of the disease.²

Children may initially appear to develop typically before experiencing a plateau and subsequent loss of acquired abilities. Disease progression varies, but the condition is associated with substantial neurologic deterioration and shortened life expectancy.^2,3

Rebisufligene etisparvovec uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the SGSH gene to the patient’s cells. The delivered gene enables cells to produce sulfamidase, supporting the breakdown of heparan sulfate and reducing its harmful accumulation in the body and brain.¹

The therapy’s systemic delivery is designed to allow the AAV9 vector to reach the central nervous system at levels sufficient to produce a therapeutic effect. Rebisufligene etisparvovec is administered in a health care setting equipped to identify and manage infusion-related reactions.¹

Cognitive Outcomes Supported Approval

The safety and efficacy of rebisufligene etisparvovec were evaluated in an open-label, single-arm, multicenter clinical study involving pediatric patients with MPS IIIA. The broader clinical development program evaluated the treatment across multiple age groups, doses, and stages of disease.⁴

For the efficacy assessment, investigators measured mean changes in cognitive scores among treated children between 2 and 5 years of age. Outcomes were compared with those from an untreated historical control cohort because the progressive and rare nature of MPS IIIA makes conventional randomized trials difficult to conduct.

Patients treated with rebisufligene etisparvovec maintained or improved cognitive function compared with the historical control group. According to the FDA, this difference represented a meaningful departure from the expected natural history of developmental plateau followed by decline during a critical period of childhood development.¹

The evidence also reinforces the importance of early diagnosis. Because MPS IIIA causes progressive and potentially irreversible neurologic injury, identifying eligible patients before extensive developmental regression could affect the degree of benefit achievable with treatment.

Safety and Monitoring Considerations

The most common adverse reactions reported in more than 5% of rebisufligene etisparvovec-treated patients included increased aspartate aminotransferase levels, nausea, vomiting, fever, decreased appetite, leukopenia, thrombocytopenia, and increased amylase levels.¹

The therapy carries an important warning for thrombotic microangiopathy, a potentially serious condition involving small-vessel injury, thrombocytopenia, and organ damage. As with other AAV-based gene therapies, there is also a theoretical long-term risk that vector genetic material could integrate into the patient’s genome and contribute to tumor development.^1,5

All patients receive corticosteroid therapy beginning 1 day before the infusion and continuing for at least 8 weeks afterward. This requirement creates an important role for pharmacists in verifying weight-based supportive regimens, assessing medication interactions, monitoring adherence, and coordinating laboratory surveillance.

Pharmacists may also support families by explaining the infusion process, reinforcing corticosteroid instructions, reviewing adverse-effect warning signs, and helping coordinate long-term follow-up. Because rebisufligene etisparvovec is administered once but requires extended safety monitoring, communication across the treatment center, specialty pharmacy, pediatric care team, and family will remain essential.

The FDA granted rebisufligene etisparvovec Orphan Drug, Fast Track, and Breakthrough Therapy designations. Its approval marks the first opportunity to intervene directly in the biological mechanism driving MPS IIIA rather than limiting care to the management of its progressive complications.¹

REFERENCES

1. FDA approves first gene therapy for pediatric patients with Sanfilippo syndrome type A. FDA. Published September 17, 2026. Accessed September 17, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type?utm_medium=email&utm_source=govdelivery

2. Mucopolysaccharidosis type III. National Organization for Rare Disorders. Accessed September 17, 2026. https://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-iii/

3. Sanfilippo syndrome. MedlinePlus Genetics. National Library of Medicine. Accessed September 17, 2026. https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-iii/

4. Phase I/II/III gene transfer clinical trial of scAAV9.U1a.hSGSH for treatment of MPS IIIA. ClinicalTrials.gov. Identifier: NCT02716246. Accessed September 17, 2026. https://clinicaltrials.gov/study/NCT02716246

5. Considerations for the long-term monitoring of patients following administration of human gene therapy products. FDA. January 2020. Accessed September 17, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/long-term-follow-after-administration-human-gene-therapy-products