Ultragenyx UX111 Nears Decision After FDA Acceptance

Ultragenyx’s UX111 BLA Accepted by FDA, PDUFA Set for September 2026

Ultragenyx Pharmaceutical Inc. has announced that the U.S. Food and Drug Administration has accepted for review its resubmitted Biologics License Application (BLA) for UX111 (rebisufligene etisparvovec), an investigational AAV9 gene therapy for the treatment of Sanfilippo syndrome Type A. The application is seeking accelerated approval, and the agency has assigned a PDUFA action date of September 19, 2026. UX111 had previously been granted Priority Review in February 2025.

Long-term data support durability and clinical benefit

The regulatory milestone follows a prior review cycle in which the FDA identified the need for additional data. According to the company, the resubmission includes updated long-term clinical evidence supporting the therapy’s efficacy and safety, primarily derived from the Phase 1/2/3 Transpher A study, with additional durability data from an ongoing long-term follow-up study (NCT04360265) and supportive evidence from a separate higher-dose cohort study (NCT04088734).

During earlier interactions, the FDA acknowledged that neurodevelopmental outcomes observed with UX111 were robust, with biomarker data providing supportive evidence. The updated dataset, presented at WORLDSymposium 2026, includes up to eight years of follow-up.

These data show sustained clinical benefit compared with the natural disease course, which is characterized by progressive neurodegeneration. Patients treated with UX111 demonstrated continued improvement across multiple clinical endpoints and biomarkers, alongside an acceptable safety profile. The findings suggest a durable treatment effect in a disease with no approved therapies.

Gene therapy approach targets underlying enzyme deficiency

UX111 is a one-time, intravenously administered gene therapy designed to address the root cause of Sanfilippo syndrome Type A. The condition arises from mutations in the SGSH gene, leading to deficiency of the sulfamidase enzyme and accumulation of heparan sulfate in the brain.

The therapy uses a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to patient cells. Once transduced, these cells produce the missing enzyme, which is secreted and taken up by surrounding cells, including neurons. The enzyme is then transported to lysosomes, where it helps reduce substrate accumulation and limit cellular damage.

Manufacturing and regulatory designations

If approved, UX111 will be manufactured entirely in the United States, including production at Andelyn Biosciences in Ohio and Ultragenyx’s facility in Massachusetts.

The program has received multiple regulatory designations, including Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Rare Pediatric Disease, and Orphan Drug status in the U.S., as well as PRIME and Orphan designations in the European Union.

High unmet need in a rare pediatric disorder

Sanfilippo syndrome Type A is a rare, inherited lysosomal storage disorder that primarily affects the central nervous system. Symptoms typically begin in early childhood with developmental delay, followed by progressive cognitive, behavioral, and motor decline.

The disease is uniformly fatal, with a median life expectancy of approximately 15 years. It is estimated to affect 3,000 to 5,000 patients in commercially accessible regions worldwide. There are currently no approved treatments, highlighting the significant unmet medical need.

The FDA’s upcoming decision on UX111 will determine whether the therapy becomes the first approved treatment option for this condition.

Reference

Ultragenyx Announces U.S. FDA Acceptance of BLA Resubmission for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA), 02 April 2026, Ultragenyx Announces U.S. FDA Acceptance of BLA Resubmission for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA)—Ultragenyx Pharmaceutical Inc.