Ultragenyx Receives FDA Complete Response Letter for UX111 Gene Therapy, Delaying Approval to 2026.

Ultragenyx Pharmaceutical has received a Complete Response Letter from the FDA for its UX111 gene therapy to treat Sanfilippo syndrome type A. The FDA cited issues with manufacturing processes, delaying potential approval to 2026. Ultragenyx plans to address the issues and resubmit the Biologics License Application. Despite the setback, the FDA's positive clinical data assessment suggests prospects for approval remain strong.

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its Biologics License Application (BLA) for UX111 (ABO-102), a gene therapy intended to treat Sanfilippo syndrome type A (MPS IIIA). The FDA cited specific chemistry, manufacturing, and controls (CMC) observations that are deemed resolvable. While the FDA acknowledged the robustness of the clinical and biomarker data, the CRL has delayed the potential approval of UX111 to 2026 [1].

Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx, stated, "Our goal is to get UX111 to patients as quickly as possible, knowing how critical this first therapy is to the Sanfilippo community. We have been diligently responding to the recent CMC observations and our priority is to resolve them so that we can resubmit the BLA as soon as possible. We believe the CMC observations are readily addressable and many have already been addressed" [1].

The CRL 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 related to facilities and processes and are not directly related to the quality of the product. Ultragenyx will work with the FDA over the next few months to resolve these observations and anticipates a 6-month review period following the resubmission [1].

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].

About UX111, a novel in vivo gene therapy in Phase 1/2/3 development, is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of heparan sulfate in the brain. The therapy 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 [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 [1].

Ultragenyx is committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has 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].

References:
[1] https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene
[2] https://www.nasdaq.com/articles/ultragenyx-pharmaceutical-inc-receives-complete-response-letter-fda-ux111-gene-therapy