FDA Approves First Treatment for Sanfilippo Syndrome Type A

The FDA approved rebisufligene etisparvovec-hopf (Fayuvi; Ultragenyx), also known as UX111, last week, on September 17, making it the first FDA-approved treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), or Sanfilippo syndrome type A.¹

MPS IIIA is a rare inherited disease that progressively damages the brain and nervous system, resulting in children losing cognitive, language, and other developmental abilities over time. Before last week’s decision, treatment was limited to managing symptoms, as there was no FDA-approved therapy targeting the underlying course of the disease.

UX111 is a 1-time, intravenous gene therapy that uses an adeno-associated virus serotype 9, a modified, noninfectious virus, to deliver a working copy of the SGSH gene into patients’ cells. This enables their cells to produce sulfamidase, the enzyme missing or deficient in patients with MPS IIIA, allowing heparan sulfate to be properly broken down in lysosomes and reducing its harmful buildup throughout the body and brain.

The treatment is administered in a health care setting equipped to manage infusion reactions. All patients receive corticosteroid treatment starting 1 day before the infusion, which is continued for a minimum of 8 weeks afterward.

“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,” said Karim Mikhail, BPharm, MSc, director of the Center for Biologics Evaluation and Research, in a news release.¹

Transpher A Data Support Approval

The approval was supported by data from the Transpher A trial (NCT02716246) and long-term follow-up studies, which demonstrated clinical benefit relative to the decline observed in natural history.² The data also showed a durable treatment effect across clinical assessments and multiple biomarkers while maintaining an acceptable safety profile; clinical data extend to nearly 8 years of follow-up.

Investigators assessed clinical efficacy based on the mean change in Bayley-III Cognitive raw score from 24 to 60 months of age. They compared patients with Sanfilippo syndrome type A treated with UX111 from the modified intention-to-treat population (n = 17) with untreated patients from an external, comparable natural history cohort (n = 27).

Across all age groups, biochemical efficacy in replacing the missing enzyme was demonstrated by reduced accumulated cerebrospinal fluid heparan sulfate levels. Specifically, patients treated with UX111 demonstrated a 23.5-point higher cognitive score during the study period (P < .0001), supporting the efficacy of UX111 for traditional approval.

Safety Profile and Long-Term Considerations

UX111’s safety profile was evaluated in pediatric patients who received a single intravenous infusion across clinical studies.¹ The most common adverse reactions were increases in liver enzymes and amylase, fever, nausea, vomiting, and decreased white blood cell and platelet counts. In addition, as with other adeno-associated virus-based gene therapies, there is a potential long-term risk that the administered genetic material could integrate into the genome and potentially lead to tumor development.

At the same time, experts emphasized the importance of the recent approval for this patient population.

"The approval of Fayuvi reflects years of research from scientists and developers, as well as unwavering support from so many families and patient organizations in the face of a devastating, universally fatal disease with no treatment options,” Emil D. Kakkis, MD, PhD, CEO and president of Ultragenyx, said in a statement.² “We recognize the profound urgency of making this therapy available to families, and our focus now is on supporting timely access in the US as we work closely with treatment centers and payers to support families on the gene therapy treatment journey.”

References

1. FDA approves first gene therapy for pediatric patients with Sanfilippo syndrome type A. News release. FDA. September 17, 2026. Accessed September 21, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type
2. Ultragenyx announces approval of Fayuvi gene therapy, the first-ever FDA-approved treatment for Sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx. September 17, 2026. Accessed September 21, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-approval-fayuvitm-gene-therapy-first-ever