Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE) on Tuesday announced new long‑term data from clinical studies evaluating UX111 (rebisufligene etisparvovec).
It is an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA), a fatal neurodegenerative lysosomal storage disorder.
What is MPS IIIA?
MPS IIIA is caused by mutations in the SGSH gene, leading to a deficiency of the enzyme heparan N-sulfatase, causing toxic accumulation of heparan sulfate in the brain and body.
It causes rapid cognitive decline, severe behavioral issues, and premature death.
Trial Data
The results demonstrate substantial and durable biomarker improvements and meaningful functional benefits compared with natural history.
Cognitive function, expressive and receptive communication, and fine and gross motor skills were measured using 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 (n=17) demonstrated a +23.2 point (p<0.0001) treatment effect in the mean Bayley-III cognitive raw score compared to natural history data during 24-60 months of age.
In addition to cognitive function, clinical improvements were also observed.
On a separate caregiver-reported outcome utilizing Vineland 3, there were comparable improvements in the communication, motor, and personal subdomains.
Eight children reached a 36‑month cognitive developmental age, enabling higher‑level testing—none of the natural‑history patients reached this milestone, the company said in a press release on Tuesday.
Patients with older age or having more advanced disease at the time of treatment (n=10) showed retention of functional abilities in at least one of three areas at the time of last assessment that exceeded typical decline patterns in untreated children with Sanfilippo syndrome Type A.
As of the September 2025 cutoff date, the median reduction in cerebrospinal fluid heparan sulfate (CSF-HS) exposure was 63.98% (p<0.001).
CSF-HS is a biomarker for monitoring neurodegenerative lysosomal storage disorders.
The majority of children treated (88.2% of younger patients and 81.5% of the overall efficacy set) achieved a 50% or greater reduction.
UX111 was well-tolerated, and the safety profile remains favorable.
What Next?
These longer-term data were included in the resubmitted Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for UX111.
The company anticipates up to a 6-month review period from the date of resubmission, with a PDUFA date expected in the third quarter of 2026.
Price Action: RARE stock is up 0.08% at $24.78 at the last check on Tuesday, according to Benzinga Pro data.
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