FDA Approves First Gene Therapy for Sanfilippo Syndrome Type A

FDA has approved rebisufligene etisparvovec-hopf (Fayuvi), developed by Ultragenyx Pharmaceutical, as the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A, the agency announced September 17, 2026.¹ MPS IIIA is a rare, inherited disease that progressively damages the brain and nervous system, causing children to lose cognitive, language, and other developmental abilities over time. Until now, treatment was limited to managing symptoms, with no FDA-approved therapy designed to change the disease's underlying course, according to the agency.¹

"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 Kyle Diamantas, JD, acting FDA commissioner, in an agency press release.¹ "Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A, and this milestone reflects [FDA's] commitment to action."

How does Fayuvi work?

Fayuvi is a one-time, intravenous gene therapy that uses a modified, non-infectious adeno-associated virus serotype 9 (AAV9) to deliver a working copy of the SGSH gene into a patient's cells. This action enables cells to produce sulfamidase, the enzyme that is missing or deficient in MPS IIIA, allowing heparan sulfate to be properly broken down in lysosomes and reducing its harmful buildup throughout the body and brain.¹

What clinical data supported approval?

Fayuvi's safety and effectiveness were evaluated in the open-label, single-arm, multicenter Transpher A trial (NCT02716246) in pediatric patients with MPS IIIA, in which clinical efficacy was assessed based on mean change in Bayley-III cognitive raw score from 24 to 60 months of age.¹^,² In the modified intention-to-treat population (n=17), Fayuvi-treated patients scored 23.5 points higher than an external natural history cohort of untreated patients (n=27), a meaningful divergence (p<0.0001) from the expected pattern of developmental plateau followed by decline.¹^,³ Biochemical efficacy was also demonstrated through reductions in cerebrospinal fluid heparan sulfate levels across all age groups, with clinical data extending to nearly 8 years of follow-up.³

What other significance did FDA state about the approval?

"Achieving meaningful neurodevelopmental benefit through a single intravenous administration represents a significant scientific milestone, demonstrating that systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutically relevant levels in pediatric patients," said Megha Kaushal, MD, MSc, acting deputy director of FDA's Office of Therapeutic Products, in the agency release.¹

Karim Mikhail, BPharm, MS, director of FDA's Center for Biologics Evaluation and Research, added that the approval reflects years of waiting by parents and clinicians for a treatment able to slow the disease's relentless regression, calling it a meaningful step forward for children with MPS IIIA and for the broader promise of gene therapy in rare, devastating diseases.¹

What are the safety considerations?

The most common adverse reactions, reported in more than 5% of patients, included increases in liver enzymes, nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts, and increased amylase.¹ Important safety warnings include the risk of thrombotic microangiopathy and, as with other AAV-based gene therapies, a potential long-term risk that the inserted genetic material could integrate into the genome and lead to tumor development.¹ Fayuvi must be administered in a healthcare setting equipped to manage infusion reactions, and all patients receive corticosteroid treatment beginning 1 day before infusion and continuing for a minimum of 8 weeks afterward, according to the agency.¹

What's next for Fayuvi?

Fayuvi was granted orphan drug, fast track, and breakthrough therapy designations. The approval marks Ultragenyx's second approved gene therapy. The company also received a priority review voucher in connection with the approval.¹^,³

Fayuvi is manufactured in the United States at Ultragenyx's Bedford, Mass., facility and at Andelyn Biosciences' Columbus, Ohio, facility. It is the first FDA-approved gene therapy made using Andelyn's AAV Curator Platform, according to Andelyn.³^,⁴ "We are proud to manufacture an FDA-approved gene therapy for commercial use using an AAV Curator Platform process," said Wade Macedone, CEO of Andelyn Biosciences, in a company press release.⁴

What are the limitations?

Efficacy was assessed against an external historical natural history cohort rather than a randomized, concurrent control group. The approved indication is limited to pediatric patients with preserved neurodevelopmental function.³

References

1. FDA. FDA approves first gene therapy for pediatric patients with Sanfilippo syndrome type A. Press release. Published September 17, 2026. Accessed September 18, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type
2. Phase I/​II/​III gene transfer clinical trial of scAAV9.U1a.hSGSH. ClinicalTrials.gov; NCT02716246. Updated August 21, 2026. Accessed September 18, 2026. https://clinicaltrials.gov/study/NCT02716246
3. Ultragenyx Pharmaceutical. Ultragenyx announces approval of FAYUVI gene therapy, the first-ever FDA-approved treatment for Sanfilippo syndrome type A (MPS IIIA). Press release. Published September 17, 2026. Accessed September 18, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-approval-fayuvitm-gene-therapy-first-ever
4. Andelyn Biosciences. Andelyn and its Curator Platform achieve first FDA-approved commercial gene therapy manufacturing milestone following FDA approval of Ultragenyx's FAYUVI to treat Sanfilippo syndrome type A (MPS IIIA). Press release. Published September 18, 2026. Accessed September 18, 2026. https://www.andelynbio.com/news-media/andelyn-biosciences-and-its-curator-platform-achieves-first-fda-approved-commercial-gene-therapy-manufacturing-milestone