FDA approved Fayuvi (rebisufligene etisparvovec-hopf), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A.

Until today, treatment for MPS IIIA was limited to managing symptoms, as there was no FDA-approved therapy designed to change the underlying course of the disease.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.

Fayuvi was granted orphan drug, fast track, and breakthrough therapy designations, and FDA granted the approval to Ultragenyx Pharmaceutical, Inc.

What is Fayuvi?

Fayuvi is a one-time, intravenous gene therapy that uses a modified, non-infectious virus called an adeno-associated virus serotype 9 (AAV9) to deliver a working copy of the SGSH gene into a patient's cells.¹ This enables the body's 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.

Fayuvi is administered in a healthcare setting equipped to manage infusion reactions, with all patients receiving corticosteroid treatment beginning one day before the infusion and continuing for a minimum of eight weeks afterward.¹

In a discussion with Pharmaceutical Executive, Lisa Bollinger, chief medical officer at Polaryx, touched on the importance of FDA committing to approving rare disease treatments, saying, "What we've really seen over the last couple of years is a commitment to developing therapies for rare diseases, evidenced by the formation of a rare disease review division within the centers at CBER, as well as some additional offices like the Rare Disease Hub and Rare Disease representation within the Office of the Commissioner."

What was the approval based on?

The safety and effectiveness of Fayuvi were evaluated in an open-label, single-arm, multicenter clinical study in pediatric patients with MPS IIIA.² The study measured mean changes in cognitive scores in patients between the ages of two and five years. In the study, Fayuvi-treated patients maintained or improved cognitive function compared to an untreated historical control cohort, marking a meaningful divergence from the expected natural disease course of plateau and decline during this critical developmental window.²

"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. This approval underscores OTP's and FDA's commitment to applying rigorous evidentiary standards as the field of gene therapy continues to advance," said Megha Kaushal, M.D., M.Sc., acting deputy director of the Office of Therapeutic Products.

The safety of Fayuvi was evaluated in pediatric patients who received a single intravenous infusion across clinical studies. 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.^1,2

"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. Parents and clinicians have been waiting far too long for an option," said Karim Mikhail, B. Pharm., M.S., director of the Center for Biologics Evaluation and Research. "Today's approval of Fayuvi 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 the most urgent."

The approval adds Fayuvi to a growing roster of one-time gene therapies aimed at rare, previously untreatable pediatric conditions, underscoring the continued momentum behind AAV-based approaches.

Sources

1. FDA Approves First Gene Therapy for Pediatric Patients with Sanfilippo Syndrome Type A Food and Drug Administration September 17, 2026, https://www.globenewswire.com/news-release/2026/09/17/3364349/0/en/fda-approves-first-gene-therapy-for-pediatric-patients-with-sanfilippo-syndrome-type-a.html
2. Ultragenyx Announces Positive Longer-Term Data Demonstrating Treatment with UX111 Gene Therapy Results in Sustained, Significant Reductions in CSF-HS and Continued Meaningful Improvements in Clinical Function Across Multiple Developmental Domains in Children with Sanfilippo Syndrome (MPS IIIA) Ultragenyx February 3, 2026, https://ir.ultragenyx.com/node/18341