Ultragenyx Pharmaceutical Resubmits UX111 BLA for Sanfilippo Syndrome

Ultragenyx Pharmaceutical RARE announced the resubmission of its biologics license application (“BLA”) to the FDA seeking accelerated approval for AAV gene therapy candidate UX111, which is being developed for the treatment of Sanfilippo syndrome type A (MPS IIIA).

The company initially submitted the BLA in December 2024 under the accelerated approval pathway, and the FDA granted priority review in February 2025.

Over the past year, RARE’s shares have declined 44.6% against the industry’s 15.2% rise.

RARE’s BLA Resubmission Address Issues in CRL

The FDA issued a Complete Response Letter (CRL) for the UX111 BLA in July 2025 requesting additional information and improvements regarding certain chemistry, manufacturing, and controls (“CMC”) elements, along with findings from the manufacturing facility inspections. Per Ultragenyx Pharmaceuticals, the issues raised were facility- and process-related, which were readily addressable and not tied to product quality.

The resubmitted BLA addresses all CMC observations cited in the CRL. It also includes longer-term data across multiple measures of neurological benefit to support an intermediate clinical endpoint for accelerated approval, further reinforced by cerebral spinal fluid (CSF) heparan sulfate (HS) and other biomarker data, in line with agreements reached with the FDA during the most recent clinical review.

A target action date by the FDA is expected to be assigned within a month. RARE anticipates up to a six-month review period from the date of resubmission per FDA regulations, with a target action date expected in the third quarter of 2026. UX111 would be the first available therapy for sanfilippo syndrome type A if approved.

Rationale Supporting RARE’s UX111 BLA Submission

The original BLA submission was backed by data, including findings from the phase I/II/III Transpher A study. The study demonstrated that treatment with UX111 led to a rapid and lasting reduction in HS levels in the CSF of patients with MPS IIIA. Additionally, maintaining lower CSF HS levels over time was linked to improved long-term cognitive development, contrasting with the decline observed in natural history data. The investigational gene therapy was overall well-tolerated in the study. Adverse events related to treatment with the candidate were mostly mild to moderate in severity.

The CRL did not raise concerns about the clinical data or inspections but requested the inclusion of updated clinical data from current patients in the resubmission.

The FDA acknowledged the robustness of the submitted neurodevelopmental outcome data and the supportive nature of the biomarker findings. The updated clinical data in the BLA include an additional year of patient follow-up. These data continue to demonstrate durable treatment benefits across multiple biomarkers and increasing separation from untreated, natural-history outcomes.

More on Ultragenyx’s UX111

UX111 is a novel in vivo gene therapy to treat the underlying sulfamidase enzyme deficiency, which is responsible for the abnormal accumulation of HS in the brain that leads to progressive cell damage and neurodegeneration in children with MPS IIIA.

UX111 enjoys the Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease and Orphan Drug designations in the United States. In the European Union, the candidate has been granted the PRIME and Orphan Medicinal Product designations.

MPS IIIA is a rare, fatal lysosomal storage disorder with no approved treatment, primarily affecting the central nervous system. Approximately 3,000 to 5,000 patients in commercially accessible geographies are affected by this disease, with a median life expectancy of 15 years.

RARE’ Zacks Rank & Stocks to Consider

Ultragenyx Pharmaceutical currently carries a Zacks Rank #3 (Hold).

Some better-ranked stocks in the biotech sector are Assertio Holdings ASRT, Alkermes ALKS and Soleno Therapeutics SLNO, each currently sporting a Zacks Rank #1 (Strong Buy). You can see the complete list of today’s Zacks #1 Rank stocks here.

Over the past 60 days, estimates for Assertio’s 2026 loss per share have narrowed from 30 cents to 28 cents. ASRT shares have declined 3% over the past year.

Assertio’s earnings beat estimates in one quarter, and missed in the remaining three quarters, with the negative average surprise being 35.21%.

Over the past 60 days, estimates for Alkermes’ 2026 earnings per share have increased from $1.54 to $1.91. ALKS shares have risen 10.2% over the past year.

Alkermes’ earnings beat estimates in three of the trailing four quarters, and missed in the remaining one, with the average earnings surprise being 4.58%.

Over the past 60 days, estimates for Soleno Therapeutics’ 2026 earnings per share have increased from $3.48 to $3.87. SLNO shares have declined 20.5% over the past year.

Soleno Therapeutics’ earnings beat estimates in three of the trailing four quarters, and missed in the remaining one, with the average negative earnings surprise being 0.63%.

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