The FDA granted standard full approval to Ultragenyx's FAYUVI gene therapy for Sanfilippo syndrome Type A on Sept. 17, the first-ever treatment for the fatal neurodegenerative disease, based on a 23.5-point cognitive score advantage over natural history (p<0.0001). The approval credits Abeona Therapeutics, which developed the AAV9 vector's clinical program before out-licensing it to Ultragenyx under funding pressure.
The FDA granted standard full approval to Ultragenyx Pharmaceutical's FAYUVI (rebisufligene etisparvovec-hopf) on Sept. 17, making it the first therapy ever cleared for mucopolysaccharidosis type IIIA, or Sanfilippo syndrome Type A — a disease with a median life expectancy of 15 years and no prior treatment that altered its course.
The approval also settles a decade-long development arc that began in an academic lab, passed through Abeona Therapeutics (NASDAQ: ABEO), and reached patients only after Abeona out-licensed the asset when it could not fund the program itself. Ultragenyx named Abeona's development and leadership team in its approval statement, and Abeona issued a congratulatory release the following morning calling the approval a validation of its foundational R&D and clinical development in MPS IIIA.
"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 approval. "It is additionally gratifying in that this vector was first developed at Nationwide Children's more than a decade ago."
The vector was developed by Haiyan Fu, PhD, and Doug McCarty, PhD, during their tenures at Ohio State University and Nationwide Children's Hospital, then licensed to Abeona. Ultragenyx said in its release that "when funding constraints arose despite positive clinical data, Abeona made the pivotal decision to out-license the asset to Ultragenyx, ensuring this vital treatment reached the finish line for patients."
FAYUVI is a single-dose intravenous AAV9 gene therapy that delivers a functional copy of the SGSH gene, restoring the sulfamidase enzyme that Sanfilippo A patients cannot produce. Without it, heparan sulfate accumulates in cells and destroys the central nervous system.
The efficacy basis for full — not accelerated — approval rests on the pivotal Transpher A trial and long-term follow-up extending to nearly eight years. In the modified intention-to-treat population of 17 patients, FAYUVI produced a 23.5-point higher Bayley-III Cognitive raw score versus an external natural history cohort of 27 untreated patients, with p<0.0001, meaning less than a 0.01% probability the result was random. Treated patients also showed sustained reductions in cerebrospinal fluid heparan sulfate across all age groups.
Fierce Pharma reported that eight children reached a 36-month cognitive development age, while no one in the natural history cohort reached that milestone. Among 10 older or later-stage children, retention of functional ability was observed in at least one of three assessed areas at last evaluation, exceeding typical decline patterns in untreated patients.
The safety profile carries real weight. Liver enzyme elevations occurred in 85% of patients, requiring corticosteroids before and after infusion and intensive monitoring. Vomiting hit 67%, abnormal behavior 56%, diarrhea 48% and pyrexia 41%. The label carries warnings for thrombocytopenia, thrombotic microangiopathy, infusion reactions and a potential malignancy risk from AAV vector DNA integration into the genome. Platelet counts must be checked weekly for four weeks, then monthly for six months.
FAYUVI is Ultragenyx's second gene therapy approval and sixth FDA approval overall. The company received a Priority Review Voucher, a transferable asset that moves a future application to the front of the review queue and has historically sold for $100 million or more on the open market.
Commercial product is expected to ship to U.S. Qualified Treatment Centers within 30 to 60 days, supported by the company's UltraCare program. FAYUVI is manufactured entirely in the U.S., at Ultragenyx's Bedford, Massachusetts gene therapy facility and at Andelyn Biosciences in Columbus, Ohio. Ultragenyx estimates 3,000 to 5,000 patients in commercially accessible geographies.
The approval follows a rejection. The FDA declined to approve the therapy in 2025 over manufacturing issues at Ultragenyx's own facility and a third-party manufacturer, and the agency accepted the resubmission in April under priority review. Acting FDA Commissioner Kyle Diamantas called the clearance "a historic moment for children and families living with MPS IIIA."
The win lands against a difficult backdrop for Ultragenyx. Its Angelman syndrome candidate apazunersen failed Phase 3 in the Aspire trial this month, sending the stock to an all-time low and prompting the company to weigh "significant expense reductions." TipRanks data shows the most recent analyst rating on RARE is Hold with a $19.00 price target, against a market capitalization of $1.29 billion. The stock traded up 12.58% on the approval.
The read-through extends past both companies. The FDA has now cleared Denali Therapeutics' Avlayah for Hunter syndrome (MPS II) and walked back a request for Regenxbio to add a control arm to its MPS II gene therapy RGX-121, though that refiling was later stalled by a clinical hold after a safety signal in a sister MPS I program. For a sector where Abeona's own funding gap nearly killed a therapy that now has full approval, the precedent matters more than the individual label.
Abeona has not disclosed any economic interest in FAYUVI or a royalty on net sales, and no milestone payment tied to the approval has been confirmed. Investors will watch Ultragenyx's launch execution through the QTC network over the next 30 to 60 days, and any disclosure from Abeona on retained economics, for the next leg of the story.
This article is for informational purposes only and does not constitute investment advice.
