FDA Issues Complete Response Letter for Ultragenyx's UX111 Gene Therapy; Plans to Resubmit BLA in 2026.

Ultragenyx Pharmaceutical Inc. received a Complete Response Letter from the FDA for UX111, a gene therapy for Sanfilippo syndrome type A. The FDA acknowledged the therapy's robust clinical data and supportive biomarker data, but cited specific chemistry, manufacturing, and controls (CMC) related observations. Ultragenyx plans to address the CMC observations and resubmit the BLA, aiming for a potential approval in 2026. The delay may impact the company's revenue projections and market positioning.

Title: Ultragenyx Pharmaceutical Inc. Faces FDA Setback for UX111 Gene Therapy

Ultragenyx Pharmaceutical Inc. has received a Complete Response Letter (CRL) from the FDA for its Biologics License Application (BLA) for UX111, a gene therapy intended to treat Sanfilippo syndrome type A. The FDA acknowledged the robustness of the clinical data and supportive biomarker evidence but cited specific chemistry, manufacturing, and controls (CMC) related observations that need to be addressed.

The CRL, issued on July 11, 2025, highlighted manufacturing issues that require additional information and improvements. Despite this, the FDA clinical reviews recognized the strength of the clinical and biomarker data supporting the application. CEO Emil D. Kakkis stated that the company is addressing the CMC observations and aims to resubmit the BLA promptly, with an anticipated resolution timeline of several months.

The therapy, designed to correct the SGSH enzyme deficiency causing MPS IIIA, a severe neurological condition with currently no approved treatments, has received several designations, including Regenerative Medicine Advanced Therapy and Orphan Drug designations in the U.S. and EU.

The issuance of the CRL indicates that the FDA found deficiencies in the application, which could negatively impact the company's reputation and the perceived viability of UX111. The delay in potential approval to 2026 could hinder the company's timelines and market entry for a critical treatment in a competitive space. Addressing the CMC-related observations may require additional resources and time, potentially affecting the company’s operations and financial stability during the resolution period.

References:
[1] https://www.nasdaq.com/articles/ultragenyx-pharmaceutical-inc-receives-complete-response-letter-fda-ux111-gene-therapy