FDA Accepts Ultragenyx’s New BLA Submission for MPS IIIA Gene Therapy UX111

The FDA has accepted Ultragenyx’s resubmission of a biologics license application (BLA) for UX111 (rebisufligene etisparvovec), an adeno-associated virus serotype 9 vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome).¹

The new Prescription Drug User Fee Act (PDUFA) action date for the BLA has been set at September 19, 2026. Notably, a previous BLA submission for UX111 was met with a complete response letter from the FDA in July 2025.² According to Ultragenyx, the CRL related to a need for additional chemistry, manufacturing and controls (CMC) information and improvements and observations from inspections of manufacturing facilities that had recently been conducted.

“The FDA’s acceptance of the BLA for UX111 brings us closer to the possibility of a first-ever therapy for Sanfilippo syndrome Type A—a milestone that we recognize cannot come soon enough for families facing this devastating diagnosis,” Emil D. Kakkis, MD, PhD, the chief executive officer and president of Ultragenyx, said in a statement.¹ “We appreciate the FDA’s prompt acceptance of the resubmission and look forward to working with the agency throughout its review in order to bring this treatment option to the Sanfilippo syndrome community as quickly as possible.”

Notably, the original UX111 BLA received priority review when it was accepted by the FDA in February of last year. Ultragenyx has stated that if the therapy is approved by the agency, the product will be manufactured exclusively in the United States, with the work being carried out at the company’s Bedford, Massachusetts gene therapy manufacturing facility and Andelyn Biosciences in Columbus, Ohio.

Ultragenyx pointed out that in the previous late cycle review the FDA had indicated its position that the BLA contained robust neurodevelopmental outcome results and that the biomarker findings added supportive evidence. The resubmitted BLA contains updated long-term clinical data that were presented this year at the 22nd Annual WORLDSymposium, held February 2 to 6, 2026, in San Diego, CA. In a subgroup of 17 treated children who were younger than 2 years of age or had earlier-stage disease at the time of dosing, investigators observed meaningful neurodevelopmental gains relative to natural history data from untreated patients with reported rapid progressor phenotypes between 24 and 60 months of age.³ The mean Bayley-III cognitive raw score showed a treatment effect of 23.2 points (P < .0001). Improvements across additional Bayley-III subscales were also observed, including receptive communication (8.1 points; P = .0076), expressive communication (11.1 points; P = .0008), fine motor function (9.0 points; P = .0026), and gross motor function (3.9 points; P = .070).

Regarding the safety profile, UX111 was deemed “well-tolerated” across all dose levels. The safety population comprised 33 patients with follow-up durations ranging from 0.6 to 8.5 years (median, 4.5 years). The most frequently reported treatment-emergent adverse events were elevations in hepatic enzyme levels. Treatment-related adverse events were largely mild to moderate in severity and resolved without intervention.

“These data continue to demonstrate a remarkable and unprecedented separation from the natural history of Sanfilippo syndrome through more than 8 years of follow-up, with children in their teens retaining skills at an age when many of their untreated peers have sadly lost their most basic abilities and succumbed to this disease,” Kakkis said in a February 2026 statement.³ “Our studies consistently show that reductions in heparan sulfate are associated with meaningful clinical benefits across multiple domains, underscoring the urgency to bring forward a treatment for families who currently have no options to stop or delay the heartbreaking and inevitable progression and loss of function associated with this disease.”

REFERENCES
1. Ultragenyx announces U.S. FDA acceptance of BLA resubmission for UX111 AAV gene therapy to treat sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx Pharmaceutical Inc. April 2, 2026. Accessed April 9, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-us-fda-acceptance-bla-resubmission-ux111
2. Ultragenyx receives complete response letter from FDA for UX111 AAV gene therapy to treat sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx Pharmaceutical Inc. July 11, 2025. Accessed April 9, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene
3. 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). News release. Ultragenyx Pharmaceutical Inc. February 3, 2026. Accessed April 9, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-positive-longer-term-data-demonstrating