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

March 9, 2020

Page last updated: June 19, 2024

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. A total of 28 children have been treated among all cohorts of the ABT-001/UX111 study. 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: Active, Not Recruiting

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 10e13 vg/kg (vector genomes per kilogram of body weight). Three patients were enrolled in this cohort.
  • Mid dose cohort: 1 x 10e13 vg/kg. Three patients were enrolled in this cohort.
  • High dose cohort: 3 x 10e13 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”.

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

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

May 2022

February 2001

“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.
This page’s content has been reviewed by Dr. Cara O’Neill, FAAP.

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