FDA Accepts Ultragenyx's Resubmitted BLA for MPS IIIA Gene Therapy UX111

This article was originally published on our sister site, CGTLive®.

The FDA has accepted Ultragenyx's resubmitted biologics license application (BLA) for UX111 (rebisufligene etisparvovec), an AAV9 vector–based gene therapy in development for mucopolysaccharidosis type IIIA (MPS IIIA), commonly known as Sanfilippo syndrome type A.¹

The new Prescription Drug User Fee Act (PDUFA) target action date has been established as September 19, 2026. The resubmission follows a complete response letter (CRL) issued by the FDA in July 2025 in response to an earlier BLA filing.² Ultragenyx has indicated that the CRL identified a need for supplemental chemistry, manufacturing, and controls (CMC) information, as well as observations stemming from inspections of the company's manufacturing facilities.

“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.”

The original UX111 BLA had been granted priority review upon its acceptance by the FDA in February of the prior year. Ultragenyx has noted that, if approved, UX111 will be manufactured solely within the United States, at the company's gene therapy facility in Bedford, Massachusetts, and at Andelyn Biosciences in Columbus, Ohio.

The company noted that during the prior late-cycle review, the FDA had indicated that the BLA contained robust neurodevelopmental outcome data and that biomarker findings provided meaningful supportive evidence. The resubmitted package incorporates updated long-term clinical data presented at the 22nd Annual WORLDSymposium, held February 2 to 6, 2026, in San Diego, California. Among a subgroup of 17 treated children who were younger than 2 years of age or had earlier-stage disease at dosing, treatment was associated with notable neurodevelopmental gains versus natural history data from untreated patients with rapid progressor phenotypes observed between 24 and 60 months of age.³ The mean Bayley-III cognitive raw score demonstrated a 23.2-point treatment effect (P < .0001), with gains on multiple Bayley-III subscales, 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