Heather Lau, MD, Executive Director of Global Clinical Development at Ultragenyx, discusses positive results regarding gene therapy UX111 for treatment of patients with Sanfilippo syndrome type A (MPS IIIA).
MPS IIIA is a severe, progressive disorder that affects the central nervous system. In people with Sanfilippo syndrome type A, the body cannot break down a large sugar molecule called heparin sulfate. Signs and symptoms usually begin in early childhood and include severe neurological symptoms such as progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. Sanfilippo syndrome type A is caused by genetic changes in the SGSH gene and is inherited in an autosomal recessive manner.
Clinical Trial and Results
The Transpher A clinical trial is an ongoing, two-year, open-label, dose-escalation, phase 1/2/3, global study assessing UX111 for the treatment of patients with MPS IIIA. Patients received the highest dose of 3 x 1013 vg/kg UX111 gene therapy delivered using AAV9 technology via a single-dose intravenous infusion. UX111 is an AAV gene therapy designed to address the underlying SGSH enzyme deficiency responsible for complications in MPS IIIA. Study endpoints include heparan sulfate (HS) levels in cerebrospinal fluid (CSF), neurodevelopmental outcomes, ganglioside levels in CSF, and brain volumes.
The data presented at the 2025 WORLDSymposium meeting included results from the modified intention to treat group (mITT) with 17 patients. Treatment with UX111 resulted in decreased levels of CSF-HS within the first month in all patients, with eight patients who reached 24 months post-treatment achieving an overall mean percent reduction from baseline of 51%.
An estimated yearly rate of change (EYC) was calculated to reflect patient rate of change in BSITD-III cognitive raw scores of cognitive function. At the data cut-off, EYC in cognitive raw scores showed a positive rate of change, indicating stability or gains from baseline in 16 of 17 patients. There was a statistically significant correlation between CSF-HS exposure and EYC in cognitive raw score.
The most common treatment-related adverse event was elevations in live enzymes, which were mild or moderate in severity. One grade 3 event of increased alanine aminotransferase was reported, but resolved.
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To learn more about MPS IIIA and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/