Ultragenyx resubmits BLA for UX111 gene therapy in Sanfilippo syndrome type A (MPS IIIA). New data shows neurologic benefits; FDA decision eyed for Q3 2026. First potential treatment.
Written By: Pharmacally Medical News Desk
Ultragenyx Pharmaceutical Inc. has resubmitted its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for accelerated approval of UX111 (rebisufligene etisparvovec), an investigational AAV9-based gene therapy for Sanfilippo syndrome type A (MPS IIIA).
The updated filing includes extended clinical follow-up data showing neurologic benefits, backed by cerebrospinal fluid (CSF) heparan sulfate reductions and supporting biomarkers. Ultragenyx aligned these as intermediate endpoints with the FDA during prior review.
Addressing a Critical Unmet Need
Sanfilippo syndrome type A, a rare pediatric neurodegenerative lysosomal storage disorder, robs children of speech, motor skills, cognition, and life median survival is just 15 years. No approved treatments exist.
Emil D. Kakkis, M.D., Ph.D., Ultragenyx’s CEO and President, stressed the urgency: “Families have no way to halt this devastating progression. We’re partnering with regulators to speed access.”
Responding to FDA’s Complete Response Letter
This follows a July 2025 CRL. The resubmission addresses FDA requests with:
- Full chemistry, manufacturing, and controls (CMC) fixes
- Long-term clinical and biomarker data
- Durable effects vs. natural history
- Favorable safety in patients
Prior FDA feedback praised robust neurodevelopmental outcomes and biomarker support for clinical benefit. Full results debut at WORLDSymposium™ 2026 in San Diego.
Regulatory Path Forward
UX111 earned Priority Review in February 2025. Expect a new PDUFA date within a month; decision targeted for Q3 2026 (up to 6-month review). Approval would mark the first MPS IIIA therapy.
About UX111
UX111, in Phase 1/2/3 trials (originally from Abeona Therapeutics), delivers a functional SGSH gene via one-time IV infusion. It restores sulfamidase enzyme, clears brain heparan sulfate buildup, and halts neurodegeneration by enabling enzyme secretion and neuronal uptake.
Key designations: RMAT, Fast Track, Rare Pediatric Disease, Orphan Drug (U.S.); PRIME/Orphan (EU).
Sanfilippo Syndrome Type A
This genetic disorder strikes early childhood due to SGSH mutations, causing lysosomal heparan sulfate accumulation worst in the brain. Symptoms: developmental delays, cognitive/language loss, behavioral issues. Affects ~3,000-5,000 patients in key markets.
References
Ultragenyx Resubmits Biologics License Application for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA) to U.S. FDA, 30 January 2026, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-resubmits-biologics-license-application-ux111-aav