Ultragenyx Receives Complete Response Letter from FDA for Sanfilippo Syndrome Gene Therapy

Ultragenyx Pharmaceutical has received a Complete Response Letter from the US FDA for its BLA for UX111 (ABO-102), a gene therapy to treat Sanfilippo syndrome type A. The FDA cited issues related to chemistry, manufacturing, and controls, as well as the need for additional data and information.

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 (ABO-102), a gene therapy treatment for Sanfilippo syndrome type A (MPS IIIA). The FDA cited specific chemistry, manufacturing, and controls (CMC) related observations that require resolution. Despite acknowledging the robustness of the clinical data and supportive biomarker evidence, this delay pushes the potential approval timeline to 2026 [1].

The CRL requested additional information and improvements related to specific aspects of CMC and observations from the recently completed manufacturing facility inspections. Ultragenyx believes these observations are readily addressable and primarily relate to facilities and processes, not product quality. The company is working with the FDA over the next few months to resolve these issues [1].

The clinical review had 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 [1].

Ultragenyx's UX111 program has received several designations, including 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. If approved, the product will be commercialized with Ultragenyx’s existing metabolic disease team [1].

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 [1].

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 [1].

The CRL will delay the potential approval of UX111 to 2026, but the company is working with urgency to resolve the observations and resubmit the BLA as soon as possible. Once resolution is achieved, the company expects to resubmit the BLA and anticipates up to a 6-month review period to follow the resubmission [1].

References:
[1] https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene