Ultragenyx Pharmaceutical’s gene therapy has shown durable improvements in patients with Sanfilippo syndrome Type A (MPS IIIA), a rare neurodegenerative disorder.
A Phase I/II/III trial (NCT02716246) of UX111 (rebisufligene etisparvovec), an investigational AAV9 gene therapy, has demonstrated 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. Data is available for up to 8.5 years after dosing, with a median follow-up of 4.8 years.
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Cognitive function, expressive and receptive communication, and fine and gross motor skills were measured using infant development scale Bayley-III and compared to natural history data from untreated patients with reported rapid progressor phenotypes. Children under two years of age or with earlier stage disease at the time of treatment demonstrated a 23.2-point increase in the mean Bayley-III cognitive raw score compared to natural history data during 24-60 months of age.
In addition to cognitive function, there were clinical improvements across four other tests. This included an 8.1-point improvement in receptive communication, an 11.1-point improvement in expressive communication, a 9.0-point improvement in fine motor skills, and 3.9-point improvement in gross motor skills.
Older patients and those with more advanced disease at the time of treatment showed retention of functional abilities in at least one of three areas. All patients retained communication, 90% retained independent ambulation and 90% maintained the ability to eat by mouth. When untreated, these functions progressively worsen and are eventually lost in late childhood and early adolescence.
UX111 was well-tolerated and the safety profile remains favourable.
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By GlobalDataDr Emil Kakkis, CEO of Ultragenyx, said: “These data continue to demonstrate a remarkable and unprecedented separation from the natural history of Sanfilippo syndrome through more than eight years of follow-up, with children in their teens retaining skills at an age when many of their untreated peers have sadly lost their most basic abilities and succumbed to this disease. Our studies consistently show that reductions in heparan sulfate are associated with meaningful clinical benefits across multiple domains, underscoring the urgency to bring forward a treatment for families who currently have no options to stop or delay the heartbreaking and inevitable progression and loss of function associated with this disease.”
The data will be delivered in an oral presentation at the WORLDSymposium 2026 on 6 February.
MPS IIIA is a rare, inherited neurodegenerative lysosomal storage disorder caused by a deficiency in the SGSH enzyme, leading to toxic accumulation of heparan sulfate. The disease is often fatal, with a median life expectancy of 15 years. Currently, there is no cure for mucopolysaccharidosis III (MPS III), and no disease-modifying therapies are available.
GlobalData anticipates there will be 10,565 diagnosed cases of MPS IIIA by 2029, with India set to have the highest prevalence of cases.
JCR Pharmaceuticals is also running a Phase I/II trial of JR-441 in MPS IIIA (NCT06095388). JR-441 is a blood-brain barrier-penetrating form of heparan N-sulfatase.
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