Ultragenyx Receives FDA Complete Response Letter for UX111 Gene Therapy for Sanfilippo Syndrome Type A.

Ultragenyx Pharmaceutical received a Complete Response Letter from the FDA for its UX111 AAV gene therapy to treat Sanfilippo Syndrome Type A. The FDA requested additional information and improvements related to CMC and manufacturing facility inspections. The company plans to address the issues and resubmit the BLA, expecting a 6-month review period. Clinical data was not noted as an issue, and the FDA acknowledged the robust neurodevelopmental outcome data and supportive biomarker data.

Title: FDA Delays Ultragenyx's UX111 Gene Therapy Approval to 2026

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for its Biologics License Application (BLA) for UX111, an AAV gene therapy treatment for Sanfilippo syndrome type A (MPS IIIA). The FDA cited specific chemistry, manufacturing, and controls (CMC) related observations that require resolution, pushing the potential approval timeline to 2026.

In the CRL, the FDA requested additional information and improvements related to specific aspects of CMC and observations from the recently completed manufacturing facility inspections. The company believes these observations are readily addressable, related to facilities and processes, and are not directly related to the quality of the product. Ultragenyx plans to work with the FDA over the next few months to resolve these issues and resubmit the BLA, with an estimated 6-month review period following the resubmission.

Clinical review has been ongoing, and the FDA has acknowledged that the neurodevelopmental outcome data provided to date are robust and the biomarker data provide additional supportive evidence. The CRL did not note any review issues related to the clinical data package nor clinical inspections, and asked that updated clinical data from current patients be included in the resubmission.

About UX111
UX111 is a novel in vivo gene therapy in Phase 1/2/3 development for Sanfilippo syndrome type A (MPS IIIA), a rare fatal lysosomal storage disease with no approved treatment that primarily affects the brain. The therapy is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. UX111 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. These transduced cells then produce the enzyme and secrete it to be taken up by other brain cells, cross-correcting the enzyme deficiency. The product was originally developed by Abeona Therapeutics and transferred to Ultragenyx to complete development. The UX111 program has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., and PRIME and Orphan medicinal product designations in the EU.

Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the brain and is characterized by rapid neurodegeneration, with onset in early childhood. Children with MPS IIIA present with global developmental delay which eventually leads to progressive cognitive, language and motor decline, behavioral abnormalities and early death. MPS IIIA is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible geographies with a median life expectancy of 15 years. MPS IIIA is caused by biallelic pathogenic variants in the SGSH gene that lead to a deficiency in the sulfamidase (SGSH) enzyme responsible for breaking down heparan sulfate, a glycosaminoglycans, which accumulate in cells throughout the body resulting in the observed rapid neurodegeneration that is associated with the disorder.

Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease.

References
1. [Ultragenyx Pharmaceutical Inc. - FDA Issues CRL for UX111](https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene)
2. [Ultragenyx Receives CRL from FDA for UX111](https://www.stocktitan.net/news/RARE/ultragenyx-receives-complete-response-letter-from-fda-for-ux111-aav-ctkumjei7ik6.html)