FDA Approves Fayuvi, First-Ever Gene Therapy for Sanfilippo Syndrome Type A
核心洞察
The FDA granted standard full approval to Ultragenyx's Fayuvi (搜索) (rebisufligene etisparvovec-hopf (搜索)) for pediatric mucopolysaccharidosis type IIIA (搜索), also known as Sanfilippo syndrome Type A (搜索).
Fayuvi (搜索) is a one-time intravenous AAV9 gene therapy delivering a functional SGSH (搜索) gene to restore the missing sulfamidase (搜索) enzyme and reduce heparan sulfate accumulation.
Approval was supported by the pivotal Transpher A trial, in which treated patients scored 23.5 points higher on Bayley-III cognitive measures than an external natural history cohort (p<0.0001).
The U.S. Food and Drug Administration (搜索) has granted standard full approval to Fayuvi (搜索) (rebisufligene etisparvovec-hopf (搜索)), also known as UX111, for the treatment of pediatric patients with mucopolysaccharidosis type IIIA (搜索) (MPS IIIA, Sanfilippo syndrome Type A (搜索)). The decision, announced September 17, 2026, makes Fayuvi the first-ever FDA-approved treatment for the disease and the second gene therapy approval for Ultragenyx Pharmaceutical Inc.
Sanfilippo syndrome Type A (搜索) is an ultra-rare, fatal lysosomal storage disease that primarily affects the brain and is marked by rapid, progressive neurodegeneration beginning in early childhood. Children typically experience progressive global developmental delay, followed by loss of cognitive, language, and motor function, ultimately leading to early death. The disease is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible geographies, with a median life expectancy of 15 years. Until this approval, treatment was limited to managing symptoms, with no FDA-approved therapy designed to change the underlying course of the disease.
Mechanism and Administration
Fayuvi (搜索) is a single-dose intravenous AAV9 gene therapy designed to deliver a functional copy of the deficient enzyme gene that can express and replace the sulfamidase (搜索) (SGSH (搜索)) enzyme. The disease is caused by a deficiency of SGSH, which results in accumulation of heparan sulfate substrate in cells and progressive damage to the central nervous system. According to the FDA, the therapy uses a modified, non-infectious adeno-associated virus serotype 9 to deliver a working copy of the SGSH gene into patient cells, enabling production of sulfamidase and allowing heparan sulfate to be properly broken down in lysosomes, reducing its harmful buildup throughout the body and brain.
The approved indication covers neurologic manifestations of MPS IIIA in pediatric patients with preserved neurodevelopmental function.
Pivotal Trial Results
The approval is supported by data from the pivotal Transpher A trial and long-term follow-up studies, which demonstrated clinical benefit relative to the decline observed in natural history, along with durable treatment effect across clinical assessments and multiple biomarkers while maintaining an acceptable safety profile. Clinical data now extend to up to nearly 8 years of follow-up.
Biochemical efficacy in replacing the missing enzyme was demonstrated by a reduction in accumulated cerebral spinal fluid heparan sulfate levels throughout the study and across all age groups. Clinical efficacy was assessed based on patients' mean change in Bayley-III Cognitive raw score from 24 to 60 months of age. Fayuvi (搜索)-treated patients from the modified intention-to-treat population (N=17) were compared with untreated patients with Sanfilippo syndrome Type A (搜索) from an external, comparable natural history cohort (N=27). Treated patients demonstrated a 23.5 point higher cognitive score over natural history during the period of study (p<0.0001), providing the efficacy basis for standard full approval.
The FDA described the supporting study as an open-label, single-arm, multicenter clinical trial in pediatric patients with MPS IIIA that measured mean changes in cognitive scores in patients between the ages of 2 and 5 years. Treated patients maintained or improved cognitive function compared with the untreated historical control cohort — a meaningful divergence from the expected natural disease course of plateau and decline during this critical developmental window.
"This gene therapy addresses a pressing unmet clinical need and offers families a promising therapeutic option," said Kevin M. Flanigan, M.D., director of the Center for Gene Therapy at Nationwide Children's Hospital and principal investigator on the study that led to its approval. "It is additionally gratifying in that this vector was first developed at Nationwide Children's more than a decade ago, and its approval highlights our commitment to developing therapies that meaningfully impact children's health."
Development History and Regulatory Path
The therapy was developed by Haiyan Fu, PhD, and Doug McCarty, PhD, during their tenures at Ohio State University/Nationwide Children's Hospital and was licensed to Abeona. When funding constraints arose despite positive clinical data, Abeona made the decision to out-license the asset to Ultragenyx. The FDA had declined to approve the therapy last year citing manufacturing concerns.
"The approval of FAYUVI (搜索) 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," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "We recognize the profound urgency of making this therapy available to families, and our focus now is on supporting timely access in the U.S. as we work closely with treatment centers and payers to support families on the gene therapy treatment journey."
Ultragenyx received a Priority Review Voucher upon the approval. Fayuvi (搜索) marks the company's sixth FDA approval overall.
Safety Profile
Elevated liver enzymes (ALT, AST, and GGT) were observed in clinical studies of Fayuvi (搜索). Labeling directs clinicians to assess liver function by clinical examination and laboratory testing prior to infusion and to administer corticosteroids to all patients before and after infusion, adjusting the regimen if abnormalities are observed. Monitoring of liver enzymes is recommended until 2 weeks after the corticosteroid taper is complete and as clinically indicated.
Decreased platelet counts were also observed; platelet counts should be assessed prior to infusion and monitored weekly for the first 4 weeks, then monthly for 6 months. Thrombotic microangiopathy has been reported in association with AAV gene therapies, and while there have been no cases associated with Fayuvi (搜索) in clinical studies, laboratory and clinical monitoring following infusion is recommended. Infusion reactions, including hypersensitivity reactions and anaphylaxis, may occur, and malignancy may occur following treatment due to potential integration of AAV vector DNA into the genome.
The most common adverse reactions (≥5%) were liver enzyme increased (85%), vomiting (67%), abnormal behavior (56%), diarrhea (48%), pyrexia (41%), white cell count decreased (30%), Cushingoid features (30%), decreased appetite (22%), platelet count decreased (19%), anemia (19%), constipation (15%), nausea (11%), amylase increased (11%), alkaline phosphatase increase (11%), seizure (11%), hepatomegaly (11%), muscle spasticity (7%), hypokalemia (7%), gait disturbance (7%), and adrenal insufficiency (7%).
Vaccines should be avoided 30 days prior to treatment and while on corticosteroid therapy. There are no data on use in pregnant women, and a negative serum pregnancy test must be confirmed before administration in females of childbearing potential. Temporary vector shedding occurs primarily through bodily fluids and waste, with handling precautions advised for 3 months after infusion.
Access and Manufacturing
Ultragenyx will provide support to help enrolled patients and caregivers navigate access through its UltraCare program, which now includes specially trained UltraCare Gene Therapy Guides to help understand insurance coverage, assist in obtaining treatment support, and answer questions about the treatment process. Fayuvi (搜索) will be available through a network of Qualified Treatment Centers — U.S.-based healthcare institutions with specialized expertise and training to administer gene therapy — and Ultragenyx expects commercial product will be available for shipment to QTCs within 30-60 days.
Fayuvi (搜索) is manufactured entirely within the U.S., at Ultragenyx's Gene Therapy Manufacturing Facility in Bedford, Massachusetts, and Andelyn Biosciences (搜索) in Columbus, Ohio.
"The U.S. FDA approval of FAYUVI (搜索) is a milestone that the Sanfilippo syndrome Type A (搜索) community spent decades fighting to achieve: the first-ever treatment for a disease that relentlessly steals a child's abilities, independence, and future," said Glenn O'Neill, president and co-founder of the Cure Sanfilippo Foundation, and Terri Klein, CNPM, MPA, president and chief executive officer of the National MPS Society.
The company said it hopes the approval will revitalize investment in other ultra-rare gene therapies, and that FDA approval is an important first step toward its long-term goal of bringing the treatment option to families of children with Sanfilippo syndrome Type A (搜索) around the world.