Ultragenyx Announces Positive Longer-Term Data Demonstrating Treatment with UX111 Gene Therapy Results in Sustained, Significant Reductions in CSF-HS and Continued Meaningful Improvements in Clinical Function Across Multiple Developmental Domains in Children with Sanfilippo Syndrome (MPS IIIA)

Rhea-AI Summary

Ultragenyx (NASDAQ:RARE) reported up to 8.5 years of follow-up for UX111 (rebisufligene etisparvovec) in MPS IIIA, showing a median 63.98% reduction in CSF heparan sulfate (p<0.001) and sustained functional benefits versus natural history, including a +23.2-point cognitive treatment effect (p<0.0001) in younger patients. UX111 was generally well tolerated (N=33; median follow-up 4.8 years). The company resubmitted a BLA to FDA in January 2026 and expects a PDUFA in Q3 2026 following up to a six-month review.

Positive

• CSF-HS -63.98% median reduction (p<0.001)
• Cognitive improvement +23.2 points vs natural history (p<0.0001)
• Majority achieved ≥50% CSF-HS reduction (81.5% overall)
• Durable follow-up up to 8.5 years
• BLA resubmitted with expected PDUFA Q3 2026

Negative

• Efficacy population limited in size (efficacy N=27)
• Gross motor improvement not statistically significant (p=0.070)
• Most common TEAEs were liver enzyme elevations
• Median safety follow-up 4.8 years with range down to 0.6 years

Key Figures

Follow-up duration: 8.5 years Younger cohort size: 17 patients Cognitive improvement: +23.2 points +5 more

8 metrics

Follow-up duration 8.5 years Maximum UX111 clinical follow-up in presented data

Younger cohort size 17 patients Children under two or earlier-stage disease at treatment

Cognitive improvement +23.2 points Bayley-III cognitive raw score vs natural history; p<0.0001

CSF-HS median reduction 63.98% Median CSF heparan sulfate exposure reduction at September 2025 cutoff; p<0.001

Dose level 3x10^13 vg/kg Highest UX111 dose evaluated across efficacy and safety sets

Efficacy set size 27 patients Overall efficacy set for CSF-HS biomarker analysis

Safety set size 33 patients Patients evaluated for UX111 safety across all doses

FDA review period up to 6 months Expected BLA review period with PDUFA in Q3 2026

Market Reality Check

Price: $24.80 Vol: Volume 3,437,322 is 20% a...

normal vol

$24.80 Last Close

Volume Volume 3,437,322 is 20% above the 20-day average of 2,858,664, indicating elevated interest ahead of this update. normal

Technical Shares are trading below the 200-day moving average of 31.92, despite the positive UX111 data release.

Peers on Argus

Key biotech peers TLX, XENE, NAMS, SLNO, and SRRK show gains between 1.07% and 6...

Key biotech peers TLX, XENE, NAMS, SLNO, and SRRK show gains between 1.07% and 6.12%, but the momentum scanner did not flag a coordinated sector move, suggesting today’s action in RARE is more company-specific around UX111 data.

Historical Context

5 past events · Latest: Jan 30 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Jan 30	BLA resubmission	Positive	-0.8%	Resubmitted UX111 BLA with longer-term data and CMC responses to FDA.
Jan 23	Equity inducement grant	Neutral	+0.4%	Issued 16,355 RSUs to new non-executive officers under inducement plan.
Jan 23	Phase III trial miss	Negative	+3.5%	Setrusumab Phase III Orbit and Cosmic failed primary fracture rate endpoints.
Jan 12	Preliminary results	Positive	+8.3%	Reported strong 2025 revenue growth and gene therapy BLA timelines.
Jan 07	Conference presentation	Neutral	-4.1%	Announced CEO presentation at J.P. Morgan Healthcare Conference with webcast.

Pattern Detected

Recent UX111 regulatory and data milestones have produced mixed short-term reactions, while broader corporate and financial updates have sometimes driven stronger upside moves.

Recent Company History

Over the past month, Ultragenyx reported preliminary 2025 revenue growth, restructuring Crysvita royalties for $400M upfront cash in late 2025, and advanced multiple gene therapy programs. The UX111 BLA resubmission on Jan 30, 2026 incorporated the same long-term biomarker and safety data now highlighted in this update. Today’s detailed UX111 efficacy and safety results build on that regulatory step, reinforcing the longer-term data package supporting the BLA and the anticipated PDUFA timing in Q3 2026.

Market Pulse Summary

This announcement highlights long-term UX111 gene therapy data showing sustained CSF-HS reductions a...

Analysis

This announcement highlights long-term UX111 gene therapy data showing sustained CSF-HS reductions and functional benefits in children with MPS IIIA over up to 8.5 years, alongside a favorable safety profile. The results support the recently resubmitted BLA and the anticipated Q3 2026 PDUFA date. In context of Ultragenyx’s growing revenue base and prior regulatory updates, key metrics to watch include regulatory feedback, durability of clinical benefit across age groups, and how UX111 integrates with the company’s broader rare disease portfolio.

Key Terms

gene therapy, aav9, lysosomal storage disorder, cerebrospinal fluid, +2 more

6 terms

gene therapy medical

"an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA)"

Gene therapy is a medical technique that involves altering or replacing faulty genes in a person's cells to treat or prevent disease. It is considered a promising area of innovation because it has the potential to provide long-term or even permanent solutions to genetic conditions. For investors, advancements in gene therapy can signal opportunities in biotech companies and emerging treatments with significant growth potential.

aav9 medical

"an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA)"

AAV9 is a harmless virus that has been reworked to act as a delivery vehicle for therapeutic genes, able to carry corrective DNA into human cells and often used for treatments that target the heart, muscles and nervous system. It matters to investors because therapies that rely on AAV9 can create significant new markets if they work, but their value depends on successful development, scalable manufacturing, safety (including immune reactions), and regulatory approval—think of AAV9 as the delivery truck whose reliability determines whether a new medicine can reach patients and generate returns.

lysosomal storage disorder medical

"a fatal neurodegenerative lysosomal storage disorder"

A lysosomal storage disorder is an inherited condition where a cell’s recycling center (the lysosome) cannot break down certain molecules, so those materials build up like trash piling up when a household garbage disposal is broken. Investors care because these disorders create clear medical needs and definable patient groups, making them attractive targets for drugs, gene therapies and diagnostics that can command regulatory attention and commercial value.

cerebrospinal fluid medical

"Treatment with UX111 Reduced Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) Exposure"

A clear fluid that surrounds and cushions the brain and spinal cord, acting like a protective bath and cleanup system that removes waste and helps circulate nutrients. For investors, cerebrospinal fluid matters because it is a common source of diagnostic markers and a route for delivering or testing neurological drugs; changes in its composition can signal disease or affect a therapy’s development, approval prospects, and market value.

heparan sulfate medical

"reductions in heparan sulfate are associated with meaningful clinical benefits"

Heparan sulfate is a long, chain-like sugar molecule found on the surface of most cells and in the spaces between them, acting like tiny antennae and Velcro that help cells communicate, stick together, and interact with proteins, including some viruses and drugs. Investors should care because it is a common biological entry point and regulator for therapies and diagnostics; drugs that target or use heparan sulfate pathways can affect efficacy, safety, and market potential in biotech and pharmaceutical development.

pdufa regulatory

"with a PDUFA date expected in the third quarter of 2026"

PDUFA, short for the Prescription Drug User Fee Act, is a law that allows drug companies to pay fees to the government to speed up the review process for new medicines. This helps bring important drugs to market more quickly, which can impact their availability and pricing. For investors, PDUFA timelines can influence the timing of a drug’s approval and potential market success.

AI-generated analysis. Not financial advice.

Data represents up to 8.5 years of follow-up and are consistent across age, dose, and genotype

BLA resubmitted to U.S. FDA in January 2026; Company expects up to six-month review period per FDA guidelines

NOVATO, Calif., Feb. 03, 2026 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. today announced new long‑term data from clinical studies evaluating UX111 (rebisufligene etisparvovec), an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA), a fatal neurodegenerative lysosomal storage disorder. The results demonstrate 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. UX111 was well-tolerated and the safety profile remains favorable.

“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,” Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “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, Treatment with UX111 Reduced Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) Exposure and Stabilized or Improved Functioning across Dose, Age, and Stage of MPS IIIA, at the WORLDSymposium™ 2026 on Friday, February 6 at 8 a.m. PST.

Clinical Improvements in Functional Abilities Compared to 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 across the other four subtests compared to natural history:

• Receptive communication (8.1-point improvement; p=0.0076)
• Expressive communication (11.1-point improvement; p=0.0008)
• Fine motor (9.0-point improvement; p=0.0026)
• Gross motor (3.9-point improvement; p=0.070)
  
  

On separate caregiver-reported outcome utilizing Vineland 3, there were comparable improvements in the communication, motor, and personal subdomains.

“There is an unmet clinical need for a therapy for this devastating disease,” said Kevin Flanigan, M.D., director of the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and a principal investigator on the study. “These results provide evidence of benefit from this gene transfer therapy, especially when delivered early.”

Eight children reached a 36‑month cognitive developmental age, enabling higher‑level testing—none of the natural‑history patients reached this milestone.

Functional Skill Retention in Later‑Stage Children
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 exceed typical decline patterns in untreated children with Sanfilippo syndrome Type A. Specifically:

• All retained communication (verbal or non-verbal) at last assessment, with a median age of 9.70 years (5.7, 15.8); median age of loss in untreated patients is ~7.6 years of age.
• 9/10 retained independent ambulation at last assessment, with a median age of 9.05 years (5.7, 15.8); median age of loss in natural history is ~11.3 years.
• 9/10 maintained the ability to eat by mouth and/or self-feed, with a median age of 9.05 years (5.7, 15.8 max).
  
  

These findings are clinically relevant as these functions progressively worsen and are eventually lost in late childhood and early adolescence.

Significant and Durable Reduction in CSF Heparan Sulfate
Levels of CSF-HS decreased within the first month following treatment with UX111 (3x10¹³ vg/kg) in the overall efficacy set (N=27), regardless of age or stage of disease progression at the time of treatment. As of the September 2025 cutoff date, the median reduction in CSF-HS exposure was 63.98% (p<0.001). The majority of children treated (88.2% of younger patients and 81.5% of the overall efficacy set) achieved a 50% or greater reduction.

Safety profile remains favorable
UX111 was generally well tolerated across all doses (N=33), including the highest dose of 3x10¹³ vg/kg, with a median follow‑up 4.8 years (range 0.6–8.5). The most frequently reported treatment-emergent adverse events (TEAEs) were elevations in liver enzymes. Treatment‑related adverse events were mostly mild or moderate and resolved spontaneously. No participants experienced infusion-related hypersensitivity or anaphylaxis, and no incidences of thrombotic microangiopathy (TMA), myocarditis, dorsal root ganglion (DRG) toxicity, or malignancy were associated with treatment.

BLA resubmitted to FDA with PDUFA date expected in Q3
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 per FDA regulations, with a PDUFA date expected in the third quarter of 2026.

About UX111 (rebisufligene etisparvovec)
UX111 (rebisufligene etisparvovec) is a novel in vivo AAV9 gene therapy in Phase 1/2/3 development for Sanfilippo syndrome type A (MPS IIIA), a rare fatal lysosomal storage disease with no approved treatment that primarily affects the brain. The therapy is designed to address the underlying sulfamidase (SGSH) enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. UX111 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. These transduced cells then secrete the functional enzyme into the tissue fluid where it can be taken up by surrounding neurons and other cells. The enzyme is taken up efficiently into other cells and is then routed to the lysosome where it can reduce the accumulation of the heparan sulfate HS and prevent the progression of lysosomal storage and consequential injury that occurs in untreated patients. The product was originally developed by Abeona Therapeutics and transferred to Ultragenyx to complete development. The UX111 program has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., and PRIME and Orphan medicinal product designations in the EU.

About the UX111 Clinical Program
The Transpher A study (NCT02716246) has enrolled and treated 28 patients across 3 dose Cohorts at 5 sites in 3 countries. The high dose Cohort 3 (3x10¹³ vg/kg) consists of 22 patients, and 17 are in the modified intent-to-treat (mITT) group. The mITT group is defined as patients who were either up to age 2 years old, or patients older than 2 years with a cognitive developmental quotient of 60 or above at time of enrollment. These patients received the highest dose of UX111.

A separate study (NCT04088734) enrolled five patients. All participants received the highest dose of 3x10¹³ vg/kg.

Subjects who participated in either clinical study were invited to enroll into a long-term follow-up study (NCT04360265). The Transpher A and long-term follow-up studies are ongoing, and patients will continue to be followed for a minimum of 5 years following treatment with UX111.

About Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo syndrome Type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the brain and is characterized by rapid neurodegeneration, with onset in early childhood. Children with MPS IIIA present with global developmental delay which eventually leads to progressive cognitive, language and motor decline, behavioral abnormalities and early death with a median life expectancy of 15 years in the rapid progressor form of MPS IIIA. MPS IIIA is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible geographies. MPS IIIA is caused by biallelic pathogenic variants in the SGSH gene that lead to a deficiency in the sulfamidase (SGSH) enzyme responsible for breaking down heparan sulfate, a sulfated glycosaminoglycans, which accumulate in cells throughout the body primarily manifesting in the observed rapid neurodegeneration that is associated with the disorder.

Forward-Looking Statements and Use of Digital Media
Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's ability to provide the requested documentation and address the comments in the CRL to the satisfaction of the FDA, the development, timing and progress of UX111, including the timing of FDA acceptance of the BLA resubmission and the timing of FDA review of any such resubmission, the timing and outcome of any FDA inspections related to UX111, the timing of future regulatory interactions related to UX111, including the outcome of the BLA resubmission, business plans and objectives for UX111, expectations regarding the tolerability and safety of UX111, and future clinical and regulatory developments for UX111 are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop UX111, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, our limited experience in operating our own manufacturing facility, the ability of the company and its third party manufacturers to comply with regulatory requirements, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.
For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 4, 2025, and its subsequent periodic reports filed with the SEC. 

In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).

Ultragenyx Contacts

Investors
Joshua Higa
ir@ultragenyx.com

Media
Jess Rowlands
media@ultragenyx.com

FAQ

What were the UX111 long-term CSF heparan sulfate results reported by Ultragenyx (RARE) in February 2026?

UX111 produced a median 63.98% reduction in CSF heparan sulfate (p<0.001). According to the company, this durable biomarker reduction was observed across ages and disease stages with 81.5% of the efficacy set achieving ≥50% reduction as of Sept 2025.

How did UX111 affect cognitive scores compared to natural history in the Ultragenyx MPS IIIA data (RARE)?

Younger or earlier-stage treated children showed a +23.2-point treatment effect on Bayley-III cognitive raw scores (p<0.0001). According to the company, this comparison used untreated natural-history rapid progressor data over ages 24–60 months.

What safety findings did Ultragenyx report for UX111 gene therapy in their February 3, 2026 release (RARE)?

UX111 was generally well tolerated; the most frequent treatment-emergent events were liver enzyme elevations. According to the company, treatment-related events were mostly mild or moderate and resolved spontaneously, with no TMA, myocarditis, DRG toxicity, or malignancy reported.

What regulatory milestone did Ultragenyx announce for UX111 (RARE) in January–February 2026?

Ultragenyx resubmitted a Biologics License Application to the FDA in January 2026 and expects a PDUFA date in Q3 2026. According to the company, a review period of up to six months is anticipated under FDA procedures.

Did UX111 show benefits for later-stage MPS IIIA patients in Ultragenyx’s data (RARE)?

Later-stage patients often retained key functions: communication, ambulation, or feeding at last assessment. According to the company, 9/10 retained independent ambulation or feeding and all retained communication at a median age around 9 years.