FDA Approves First Gene Therapy for Sanfilippo Syndrome Type A

According to a new announcement, the FDA has approved rebisufligene etisparvovec-hopf (Fayuvi) for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. Fayuvi is the first FDA-approved treatment for MPS IIIA, a rare inherited disease that progressively damages the brain and nervous system, causing children to lose cognitive, language, and other developmental abilities over time.¹

Until this approval, treatment for MPS IIIA was limited to managing symptoms, with no therapy designed to change the underlying course of the disease. Fayuvi is a one-time, intravenous gene therapy that uses a modified, non-infectious adeno-associated virus serotype 9 (AAV9) vector to deliver a working copy of the SGSH gene into a patient's cells, enabling the body to produce sulfamidase, the enzyme missing or deficient in MPS IIIA, and allowing heparan sulfate to be properly broken down in lysosomes rather than accumulating throughout the body and brain.

Trial measured cognitive outcomes in a critical developmental window

The safety and efficacy of Fayuvi were evaluated in an open-label, single-arm, multicenter clinical study in pediatric patients with MPS IIIA, building on the ongoing phase 1/2/3 Transpher A trial.^1,2 The study measured mean changes in cognitive scores in patients between 2 and 5 years of age, a critical developmental window in which the disease typically causes a plateau and decline in cognitive function.¹

Patients treated with Fayuvi maintained or improved cognitive function compared with an untreated historical control cohort, a meaningful divergence from the expected natural course of the disease during this period. The approval follows a complicated regulatory path: an earlier biologics license application for the therapy received a complete response letter from the FDA in July 2025, and the company resubmitted with additional longer-term neurologic and biomarker data in January 2026.²

Safety profile includes a boxed risk for thrombotic microangiopathy

The most common adverse reactions, reported in more than 5% of patients, were increases in liver enzymes (AST), nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts, and increased amylase. An important safety warning applies to the risk of thrombotic microangiopathy (TMA), and as with other AAV-based gene therapies, there is a potential long-term risk that the inserted genetic material could integrate into the genome and potentially lead to tumor development.

Fayuvi is administered in a health care setting equipped to manage infusion reactions. All patients receive corticosteroid treatment beginning 1 day before the infusion and continuing for a minimum of 8 weeks afterward. Fayuvi previously received orphan drug, fast track, and breakthrough therapy designations from the FDA.

"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," Karim Mikhail, B Pharm, MS, director of the FDA's Center for Biologics Evaluation and Research, said in a statement.¹ Mikhail said the approval is a meaningful step forward, not only for these children and their families, but for the promise of gene therapy to address rare and devastating diseases where the need for safe and effective treatment is most urgent.

"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," Megha Kaushal, MD, MSc, acting deputy director of the FDA's Office of Therapeutic Products, said in a statement. Kaushal said the approval underscores the office's and the FDA's commitment to applying rigorous evidentiary standards as the field of gene therapy continues to advance.¹

Frequently Asked Questions

• What is Fayuvi approved to treat? Fayuvi (rebisufligene etisparvovec-hopf) is approved for pediatric patients with MPS IIIA (Sanfilippo syndrome type A), the first FDA-approved treatment for the disease.
• How does Fayuvi work? It is a one-time intravenous AAV9 gene therapy that delivers a working copy of the SGSH gene, enabling cells to produce sulfamidase and properly break down heparan sulfate.
• What were the key trial results? Patients treated with Fayuvi maintained or improved cognitive function between ages 2 and 5 compared with an untreated historical control cohort, diverging from the disease's typical plateau-and-decline course.

References

1. US Food and Drug Administration. FDA Approves First Gene Therapy for Pediatric Patients with Sanfilippo Syndrome Type A. News release. 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

2. ClinicalTrials.gov. Gene Transfer Clinical Trial for Sanfilippo Syndrome Type A (Transpher A). NCT02716246. Accessed September 17, 2026. https://clinicaltrials.gov/study/NCT02716246