UX111 Gene Therapy | MPS IIIA | Phase I-II-III | Ultragenyx

Page last updated: July 17, 2026

Page reviewed by: Dr. Cara O’Neill, FAAP

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Summary Information

The UX111 (formerly ABO-102) Gene Therapy uses a self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the control of a U1a promoter (scAAV9.U1a.hSGSH). This therapy was developed by Haiyan Fu, PhD, and Doug McCarty, PhD, during their tenures at Ohio State University/Nationwide Children’s Hospital. The therapy was then licensed to Abeona Therapeutics for further development.

This experimental gene therapy is designed to be delivered through a one-time intravenous infusion. A tapering course of oral steroid medication (prednisone or prednisolone) is administered for a period of at least two months to reduce potential immune response to the gene therapy.

Originally, there were two studies under Abeona Therapeutics using the ABO-102 gene therapy product: ABT-001 and ABT-003. In the spring of 2022, the clinical trial ABT-003 for children with middle to advanced disease stages was stopped.

In May 2022, Ultragenyx acquired global rights to the AAV Gene Therapy ABO-102 for Sanfilippo Syndrome Type A (MPS IIIA) from Abeona Therapeutics and has assumed responsibility for the clinical programs. Enrollment is no longer open. However, patients enrolled in the original ABT-001 clinical trial (now UX111) continue to be followed for safety and efficacy. Over 28 children have been treated among all cohorts of the ABT-001/UX111 study. An additional cohort was opened for enrollment in February 2025 which incorporates additional immunomodulatory medications. More details on this study can be found below.

Although the ABT-003 study was terminated, treated patients will be followed up for 5 years post treatment. More information on this study can be found below.

Our community is grateful to the patients and families who chose to participate in clinical trials. Their participation is essential to the advancement of science that brings us closer to an approved treatment for Sanfilippo syndrome.

Study Information

Study Title: Phase I/II/III Gene Transfer Clinical Trial of cAAV9.U1a.hSGSH (formerly ABT-001)

Status: Recruiting; cohort 4 only

Trial Listing: Read this clinical trial’s information on ClinicalTrials.gov, for more details about the study.

Study design: Open label dose escalation study

Dosing cohorts (groups):

• Low dose cohort: 0.5 x 10^13 vg/kg (vector genomes per kilogram of body weight). Three patients were enrolled in this cohort.
• Mid dose cohort: 1 x 10^13 vg/kg. Three patients were enrolled in this cohort.
• High dose cohort: 3 x 10^13 vg/kg. Twenty-two patients have been enrolled in this cohort. As the study progressed, the inclusion criteria were revised to a narrowed group of children: ages 0-2 years of age or >2 years of age with a developmental quotient of >60. This youngest group of patients receiving the highest dose of gene therapy are considered to be part of the updated study name “Transpher A”.
• High dose (Cohort 4) (clinical sites in Spain only): 3 X 10^13 vg/kg. The inclusion criteria has been listed as 3 months to ≤ 2 years of age with no BSITD-III Cognitive DQ requirement, or > 2 years of age with a BSITD-III Cognitive DQ of 60 or above, or > 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ < 60.

In 2023, the study was amended to make available immunosuppression therapy at approved sites for selected participants. The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant immunosuppressive therapy.

Study Updates and Announcements

July 2026

• While the FDA continues to review its UX111 Type A gene therapy application for accelerated approval, Ultragenyx has put out this Q2 2026 quarterly update for the Sanfilippo community.

April 2026

• Ultragenyx’s resubmission of UX111 to FDA for BLA approval was accepted. FDA now formally re-starts review of the BLA, with a target action date of Sept. 19, 2026.

February 2026

• Feb. 12, 2026 – Ultragenyx received an Incomplete Response Letter (IRL) from the FDA related to its UX111 BLA resubmission. In the letter, the FDA requested additional supportive documentation related to our responses to chemistry, manufacturing, and controls (CMC) observations raised in the previous Complete Response Letter (CRL). “This information is typically provided during an inspection, and we were prepared to do so,” said Ultragenyx in a statement on social media. “We believe we have the requested documentation and are compiling it now to include in the resubmission so the review can move forward.”
• Feb. 3, 2026 – Ultragenyx announced new long‑term data from clinical studies evaluating UX111 (rebisufligene etisparvovec), an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA), a fatal neurodegenerative lysosomal storage disorder. The results demonstrate substantial and durable biomarker improvements and meaningful functional benefits compared with natural history, with consistent and highly statistically significant results across age and disease severity. UX111 was well-tolerated and the safety profile remains favorable. Read the complete statement from Ultragenyx.

January 2026

• Ultragenyx announced January 30, 2026, that it has officially resubmitted its application to the U.S. FDA seeking accelerated approval of UX111, an AAV9 gene therapy for children living with Sanfilippo syndrome type A. With this resubmission, the FDA’s six month priority review clock has now begun and a decision date is anticipated in the third quarter of 2026. Read more.

November 2025

• In its Third Quarter 2025 Financial Results and Corporate Update, Ultragenyx announced that following receipt of a Complete Response Letter (CRL), it has had constructive formal and informal discussions with the FDA. The additional clinical data requested by the agency, which will be included in the BLA, continues to show a durable treatment effect across multiple biomarkers and further clinical separation from natural history, while maintaining an acceptable safety profile. The company plans to resubmit the BLA early in 2026 and will be followed by an up to 6-month review per FDA regulations. Read the statement.

July 2025

• Ultragenyx Pharmaceutical announced on July 11, 2025, that the FDA has issued a Complete Response Letter (CRL) for its Biologics License Application (BLA) for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). In the CRL, the FDA requested that the company provide additional information and address observations made by the FDA related to aspects of Chemistry, Manufacturing and Controls (CMC). Ultragenyx believes that these observations are readily addressable, related to manufacturing facilities and processes, and are not directly related to the quality of the product. Ultragenyx will be working with the FDA over the next few months to resolve the observations. Once resolution is achieved, the company expects to resubmit the BLA and anticipates up to a 6-month review period to follow the resubmission.
• Read Ultragenyx’s press release statement.
• Letter from Ultragenyx to the Sanfilippo community regarding the CRL

February 2025

• Feb. 18, 2025 | FDA “has accepted for review the Biologics License Application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. The FDA also informed the company that they are not currently planning to hold an advisory committee meeting to discuss this application.” Read the press release here: Ultragenyx Announces FDA Acceptance and Priority Review of the Biologics License Application (BLA) for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA)
• Feb. 5, 2025 | Ultragenyx announced “new data demonstrating treatment with UX111 (ABO-102) AAV gene therapy led to a statistically significant improvement in the Bayley-IIIi raw scores for the subdomains of cognition, receptive communication and expressive communication in patients with Sanfilippo syndrome type A (MPS IIIA) compared to natural history data from untreated patients. These clinical endpoints were correlated with substantial and sustained reduction in levels of heparan sulfate (HS) in cerebrospinal fluid (CSF).” The data was presented at the WORLDSymposium 2025, which took place February 3-7 in San Diego, CA. Read the statement from Ultragenyx.

January 2025

• Jan. 15, 2025 | The two trial sites in Spain, Vall d’Hebron Barcelona Hospital Campus and Hospital Clínico Universitario de Santiago, are listed as recruiting on ClinicalTrials.gov. For contact information for each site and the central contact person, view the listing.
• Jan. 6, 2025 | Ultragenyx announced it is set to open a fourth cohort for its current Phase 1/2/3 clinical trial of AAV9 gene therapy UX111 treating children with Sanfilippo type A. Enrollment of international patients is anticipated to open Jan. 13, 2025, at two sites in Spain. At that time, sites will begin to accept inquiries about participation. In the fourth cohort, an enhanced immunomodulation regimen of additional drug(s) in combination with the gene therapy will be evaluated. Cure Sanfilippo Foundation believes that using additional drugs to control the immune response to gene therapy could be a very important step in improving safety and effectiveness of gene therapy. Read Ultragenyx’s announcement.

December 2024

• Ultragenyx announced on Dec. 19, 2024, that they have filed an application to the FDA for accelerated approval of their Sanfilippo type A gene therapy (UX111). This is the first time that any treatment for any form of Sanfilippo has been filed to the FDA for approval consideration. Over the next 8-12 months, the FDA will be closely reviewing all of the data from the clinical trial and details about the manufacturing process of the drug product. After their review, the FDA will make a decision on whether or not to grant approval for Ultragenyx’s UX111 Sanfilippo type A gene therapy. If approved, this would be the first-ever, commercially-available treatment for individuals with Sanfilippo type A. Read the announcement from Ultragenyx.

June 2024

• Ultragenyx announced that it held a successful meeting with the U.S. Food and Drug Administration (FDA), during which they reached an agreement that cerebral spinal fluid heparan sulfate is a reasonable surrogate endpoint that could support submission of a biologics license application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy for the treatment of Sanfilippo syndrome (MPS IIIA)
• Letter from Ultragenyx to Cure Sanfilippo Foundation regarding its plans to file for Accelerated Approval for UX111 with the FDA.
• A breakdown of what the plans for Accelerated Approval filing announcement mean, created by Cure Sanfilippo Foundation, for the Sanfilippo community

March 2024

• Cure Sanfilippo Foundation hosted a 90-minute town hall webinar in collaboration with the National MPS Society and Ultragenyx in which leaders from Ultragenyx shared information about the scientific learnings from its Sanfilippo Syndrome Type A Gene Therapy Program (UX111) to date. Additionally, the leaders spoke about future plans for the Type A gene therapy program and answered questions from the Sanfilippo community. Watch the webinar archive.

February 2024

• Letter from Ultragenyx to Patient Advocacy Organizations
• Ultragenyx’s Gene Therapy Ameliorates Pediatric Neurodegenerative Disorder
• Summary interim findings for Transpher A cohort:
  • All patients had reduction in toxic heparan sulfate in the spinal fluid by 1 month after treatment
  • Mean spinal fluid heparan sulfate exposure was reduced by 63% in the time-normalized area under the curve (AUC)
  • Significant correlation between sustained reductions in spinal fluid heparan sulfate levels and sustained cognitive benefit in 15 of the 17 patients in the Transpher A cohort
  • Most-frequently reported treatment-related adverse events to date were elevations in liver enzymes. Most events were mild or moderate in severity and are known to be commonly associated with AAV based gene therapies.

December 2023

• Andelyn Biosciences Selected by Ultragenyx for Late-Stage Process Performance Qualification (PPQ) Manufacturing of Novel Gene Therapy for Sanfilippo Syndrome

May 2022

• Sanfilippo Type A gene therapy ABO-102 program will continue, Ultragenyx acquires rights
• Ultragenyx Acquires Global Rights to AAV Gene Therapy ABO-102 for Sanfilippo Syndrome Type A (MPS IIIA) from Abeona Therapeutics

February 2021

• New Positive Phase 1/2 Interim Data Presented at WORLDSymposium™ Shows Neurocognitive Development of Young MPS IIIA Patients Preserved up to Three Years Following Treatment with Abeona’s ABO-102 Gene Therapy

“Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease” (formerly ABT-003)

Status: Study Terminated

Trial listing: Read this clinical trial’s information on ClinicalTrials.gov, for more details about the study.

Study design: Open label, single dose

Experimental drug: Single dose of ABO-102 (scAAV9.U1a.hSGSH) administered by intravenous injection through a peripheral limb vein at a dose of 3 X 10^13 vg/kg

This study has been closed for enrollment as of March 11, 2022 but will follow treated patients for up to 5 years post treatment.

The aim of this study was to determine the safety and explore the potential efficacy of ABO-102 gene therapy in children who were >2 years of age or at more advanced stages of their disease course. The sponsor indicated that after 1-2 years of follow up, cognitive outcomes and other measures of efficacy were not better than the natural history of Sanfilippo syndrome type A disease course. The study was closed for enrollment after treating 5 patients. Patients in the study will still have safety follow up at their local doctors’ offices.

How does this information translate to our understanding of the benefit of gene therapy for Sanfilippo syndrome?

• While early results indicate that cognitive outcomes did not improve, we do not yet know the long-term effects of the treatment on this group of children.
• This study tested a particular type of gene therapy at a particular dose, meaning that we do not know if different versions of a gene therapy (variation in promotor, transgene optimization, vector, routes of administration, etc.) or different doses could result in more beneficial outcomes for patients in the future.
• It is important to remember that there were a small number of patients in this particular study which limits our ability to understand how a larger group of patients might respond.
• This study was designed to treat children who had already experienced significant cognitive decline due to their disease, hence we can only understand the study findings in terms of this specific population. For example, this study cannot tell us how children who have a slower disease progression and preserved cognitive function at later ages would respond to the therapy.