Ultragenyx Pharmaceutical announced positive data from its pivotal and long-term follow-up studies of UX111 (ABO-102), a gene therapy for Sanfilippo syndrome type A (MPS IIIA). The therapy showed statistically significant improvements in cognitive, receptive communication, and expressive communication scores compared to natural history data, correlating with substantial reductions in heparan sulfate (HS) in cerebrospinal fluid (CSF). These findings suggest the potential for UX111 to address the unmet medical need in MPS IIIA, a rare and fatal lysosomal storage disease currently lacking approved treatments.
This news holds significant promise for children with MPS IIIA, a devastating neurodegenerative disease that typically results in early death. The demonstrated cognitive and communication improvements, along with the retention of essential functional abilities in older patients, offer a potential shift in the disease trajectory. This could translate into meaningful extensions of quality of life, potentially allowing children to maintain abilities like walking, communicating, and self-feeding, which are progressively lost in untreated individuals. These outcomes underscore the potential of gene therapy to address the root cause of the disease and provide long-term benefits.
The data show a median reduction of 65% in CSF-HS levels across all treated patients (N=27) and 66% in the modified intent-to-treat (mITT) group (N=17), with a mean follow-up of 34 and 36 months, respectively. The mITT group demonstrated a +22.7 point improvement in mean Bayley-III cognitive raw score between 24 and 60 months of age compared to a decline of -6.8 points in natural history data. Improvements were also observed in receptive and expressive communication and fine motor skills. Importantly, older children outside the mITT group retained vital functional abilities, such as communication, ambulation, and self-feeding, offering hope for slowing disease progression even in later stages. The safety profile of UX111 remained favorable, with primarily mild to moderate, reversible liver enzyme elevations reported. A Biologics License Application for accelerated approval has been filed with the FDA, with a decision expected in the second half of 2025.
The positive data for UX111 marks a potential turning point in the treatment of MPS IIIA. If approved, UX111 could become the first disease-modifying therapy for this devastating condition, offering a new standard of care. This development could also spur further research and development into gene therapies for other lysosomal storage disorders, potentially benefiting a broader population of patients with rare genetic diseases. The upcoming FDA decision will be a critical milestone, determining the availability of this promising therapy for patients and shaping the future landscape of MPS IIIA treatment.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
