Ultragenyx’s Gene Therapy Shows Long-Term Efficacy in Two Sanfilippo Studies

 

The FDA in July last year declined to approve UX111 for Sanfilippo syndrome, a rare neurodegenerative disorder, citing manufacturing issues. Ultragenyx resubmitted its application ten days ago, expecting a six month review time.

Ultragenyx Pharmaceutical’s investigational gene therapy UX111 can sustain cognitive improvements in the long run, according to data from two studies in Sanfilippo A syndrome.

The data, toplined Feb. 3 but presented Friday at the WORLDSymposium 2026, come from the Transpher A study, which enrolled 28 patients, and another trial that had five participants. All told, Ultragenyx’s analysis included 33 dosed patients, of whom 27 were given the highest UX111 dose of 3x10¹³ vg/kg. At the time of data readout, patients had been followed for up to 8.5 years.

“We are encouraged by today’s update,” analysts at William Blair told investors in a Friday note. “UX111 continues to show long-term cognitive improvements and significant reductions in CSF HS across children of different ages.” The data, they added, “continue to support the approval of UX111.”

Results showed that in children below 2 years old, or with earlier-stage disease, UX111 significantly improved cognition as demonstrated by a 23.3-point improvement in the Bailey-III scale, a validated tool used to measure communication and motor skills. As comparators, Ultragenyx used natural history data from untreated children 24 to 60 months of age who had Sanfilippo A.

UX111 also led to significantly better scores on individual domains of the Bailey-III, including receptive and expressive communication, as well as fine motor performance.

In older children, or those with more advanced disease, treatment with the gene therapy enabled functional skill retention—that is, all 10 patients given UX111 were able to maintain their current level of verbal and non-verbal communication. At the last follow-up, these patients were at a median age of 9.7 years, whereas children lose these abilities at a median age of 7.6 years if left untreated, according to Ultragenyx.

Similarly, patients on UX111 retained independent ambulation and the ability to self-feed as of the time of readout. Aside from clinical improvements, Ultragenyx also touted biomarker benefits of UX111 which led to significant reductions in heparan sulfate (HS) levels in the cerebrospinal fluid (CS) within one month of dosing. In untreated Sanfilippo, a genetic mutation leads to a buildup of HS and its products in neurons, damaging them.

In July 2025, the FDA declined to approve UX111 for Sanfilippo syndrome, noting that it needed to see “improvements” in “certain aspects” of the therapy’s chemistry, manufacturing and controls. Notably, the rejection was “not directly related to the quality of the product,” the company said at the time.

Ultragenyx resubmitted its application on Jan. 30 and expects a six-month review period. A decision could come in the third quarter of the year.

https://www.biospace.com/drug-development/ultragenyxs-gene-therapy-shows-long-term-efficacy-in-two-sanfilippo-studies