The therapy was developed at the Abigail Wexner Research Institute at Nationwide Children's Hospital in Columbus, Ohio. The program was licensed to Abeona Therapeutics in 2013 and transferred to Ultragenyx in 2022.
How MPS IIIA affects the body
Children with MPS IIIA inherit from both parents a mutation in the SGSH gene, which normally provides instructions for producing the enzyme sulfamidase. Without functioning sulfamidase, the complex sugar heparan sulfate accumulates in cells and damages nerve cells in the brain. Symptoms begin in early childhood with developmental delays before children lose already-learned skills in thinking, language, and movement, with behavioral problems appearing. According to Nationwide Children's Hospital, the disease affects 1 in 70,000 live births. Until approval, treatment was limited to symptom management; no FDA-approved therapy existed to alter the underlying disease progression.
How the approval study measures benefit
Biochemically, the effect was clear: heparan sulfate levels in cerebrospinal fluid declined by more than half in the first treatment month and remained at least half below baseline after two years in 15 of 16 children studied. Follow-up data spans a median of approximately four years, with the longest observation nearing eight years; because of the disease's rarity, numbers come from small cohorts, with longer-term results beyond this follow-up period still unknown.
Side effects and infusion precautions
Among 27 children treated at the approved dose, elevated liver enzyme levels occurred in 85 percent, vomiting in 67 percent, behavioral changes in 56 percent, diarrhea in 48 percent, and fever in 41 percent; nearly all liver values normalized. The FDA also warns of the risk of thrombotic microangiopathy and, as with other AAV gene therapies, a possible long-term risk that integrated genetic material could insert into the genome and trigger tumors; no cases of the vascular disease were observed in Fayuvi studies themselves.
According to the National MPS Society, Fayuvi is the first gene therapy for any form of MPS and the first FDA approval of a gene therapy targeting heparan sulfate in cerebrospinal fluid as a disease marker. The organization also points to its earlier work on newborn screening for MPS I and MPS II: every month without diagnosis means lost brain function that gene therapy cannot restore, said President Terri Klein. The society is now directing efforts toward newborn screening for Sanfilippo syndrome, since treatment can only save a child's development if started early enough.
Treatment centers and antibody testing
Nationwide Children's Hospital announced it would become a qualified treatment center and part of a nationwide network with necessary facilities and trained personnel for administering Fayuvi. In connection with approval, Ultragenyx received a Priority Review Voucher.