Ultragenyx Finishes Rolling Submission of BLA for Glycogen Storage Disease Gene Therapy DTX401

Ultragenyx has completed its submission of a rolling biologics license application (BLA) to the FDA for DTX401, an investigational adeno-associated virus serotype 8 (AAV8) vector gene therapy expressing the human G6PC gene that is intended to treat Glycogen Storage Disease Type Ia (GSDIa).¹

The BLA is supported by 96-week data from the randomized, placebo-controlled phase 3 GlucoGene clinical trial (NCT05139316).^1,2 Ultragenyx noted that the nonclinical and clinical modules of the BLA were submitted to the FDA in August 2025; it has now also completed submission of the chemistry, manufacturing, and controls (CMC) module of the BLA, thus finishing the BLA package.

"The completion of our rolling submission of the BLA for DTX401 is a significant step toward our commitment to deliver the first therapy that directly targets the underlying cause of GSDIa," Eric Crombez, MD, the chief medical officer at Ultragenyx, said in a statement.¹ "Despite burdensome daily dietary and cornstarch management, patients continue to face life-threatening risks from acute hypoglycemia and chronic complications impacting the liver, kidneys, gastrointestinal system, bones, and growth. We look forward to continuing our collaboration with the FDA throughout the review process to be able to provide this potentially life-changing therapy to as many people living with GSDIa as possible.”

According to data reported by Ultragenyx in September 2025, in comparison to previously reported 48-week data, the 96-week data included in the BLA package showed that patients in both the ongoing DTX401 group and the crossover placebo to DTX401 group had greater reductions in their total daily cornstarch at their most recent visit compared to baseline. Specifically, the ongoing DTX401 group showed a 60% reduction from baseline at 96 weeks, and the crossover placebo to DTX401 group showed a 64% reduction from baseline at 96 weeks. Furthermore, patients in the DTX401 group achieved a 70% mean reduction in nighttime cornstarch intake and patients in the crossover group achieved a 75% mean reduction in nighttime cornstarch intake. Ultragenyx highlighted that across both these groups, 2 of 3 patients were able to completely eliminate 1 or more nighttime cornstarch doses in the posttreatment period.

“In the second year of treatment, patients were able to further reduce cornstarch intake while continuing to maintain good glucose control," Crombez said in a September 2025 statement.² “These results are consistent with the positive data observed in the phase 1/2 study and underscore the robustness and progressive improvement of treatment effect that can potentially be achieved with this gene therapy. The ability to reduce dependence on cornstarch reflects the establishment of the liver’s ability to break down glycogen to produce glucose during times of fasting or metabolic stress. This ability to regulate glucose levels has reduced the burden of disease and potential threat of severe or fatal hypoglycemia for these patients.”

In addition to DTX401, Ultragenyx’s pipeline also includes UX111 (ABO-102), an AAV vector-based gene therapy intended to treat mucopolysaccharidosis type IIIA (MPS IIIA, also known as Sanfilippo syndrome).³ A BLA that the company submitted to the FDA for UX111 in December 2024 was notably met with a complete response letter (CRL) from the agency in July 2025.^3,4 According to Ultragenyx, the CRL related to a need for additional CMC information and improvements and observations from inspections of manufacturing facilities. The company noted its perception that the concerns were related to facilities and processes rather than to the quality of the gene therapy product itself, and that the observations were “readily addressable”. At the time that Ultragenyx initiated its rolling BLA sub mission for DTX401, it noted that it was incorporating learnings from the experience with UX111 into its BLA submission for the GSDIa gene therapy, specifically pointing out that the BLA would contain updates meant to “proactively respond” to the FDA’s observations in the UX111 CRL and at Ultragenyx’s manufacturing facilities for its gene therapy products.²

REFERENCES
1. Ultragenyx completes rolling submission of biologics license application (BLA) to U.S. FDA for DTX401 AAV gene therapy for glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. December 30, 2025. Accessed January 5, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-completes-rolling-submission-biologics-license
2. Ultragenyx initiates rolling submission of biologics license application (BLA) to U.S. FDA for DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. August 18, 2025. Accessed January 5, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-initiates-rolling-submission-biologics-license
3. Ultragenyx receives complete response letter from FDA for UX111 AAV gene therapy to treat sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx Pharmaceutical Inc. July 11, 2025. Accessed January 5, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene
4. Ultragenyx submits biologics license application to the U.S. FDA for UX111 AAV gene therapy for the treatment of Sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx Pharmaceutical Inc. December 19, 2024. Accessed January 5, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-submits-biologics-license-application-us-fda-ux111