Fayuvi (rebisufligene etisparvovec-hopf) / Abeona Therap, Ultragenyx - LARVOL DELTA

Food and Drug Administration Grants Ultragenyx's Fayuvi™ First-Ever Approval for Sanfilippo Syndrome Type A Treatment. (PubMed, Hum Gene Ther) - No abstract available

Journal • Lysosomal Storage Diseases

Today Ultragenyx announced that the European Medicines Agency (EMA) has validated the Company's Marketing Authorisation Application (MAA) for its investigational gene therapy, rebisufligene etisparvovec, for the treatment of mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome Type A. (GlobeNewswire)

EMA filing • Gene Therapies • Lysosomal Storage Diseases

Ultragenyx Pharmaceutical…announced that the U.S. Food and Drug Administration (FDA) granted standard full approval of FAYUVI (rebisufligene etisparvovec-hopf), also known as UX111, for the treatment of pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome Type A) (GlobeNewswire) - "FAYUVI is the first-ever FDA-approved treatment for Sanfilippo syndrome Type A, a progressive and fatal neurodegenerative disease, and the second gene therapy approval for Ultragenyx....The approval of FAYUVI is supported by data from the pivotal Transpher A trial and long-term follow-up studies, which demonstrated clinical benefit relative to the decline observed in natural history, along with durable treatment effect across clinical assessments and multiple biomarkers while maintaining an acceptable safety profile....Ultragenyx expects commercial product will be available for shipment to QTCs within 30-60 days."

FDA approval • Gene therapy • Launch US • Gene Therapies • Lysosomal Storage Diseases

UX111 reduced cerebrospinal fluid heparan sulfate exposure and stabilized or improved functioning in MPS IIIA (SSIEM 2026) - P1/2, P2/3, P3 | "UX111 showed a positive treatment effect and manageable safety in children with MPS IIIA across UX111 doses, age, and stage of disease at the time of treatment. Long-term follow-up continues."

CNS Disorders • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=36 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jul 2027 ➔ Mar 2029 | Trial primary completion date: Jul 2027 ➔ Mar 2029

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Development of a Highly Productive Process for a rAAV Gene Therapy to Treat MPSIIIA (ASGCT 2026) - "The resulting process represents a key advancement in the manufacturing process for UX111, with potential applicability across broader AAV-based gene therapy programs. Figure 1: Genome titer results from screening studies (abbreviated set) identified a new transfection reagent that enhances process performance."

Gene therapy • Gene Therapies • Lysosomal Storage Diseases

SYL-222 (AAV9-SGSH-SyLEC): A Novel Gene Therapy for Mucopolysaccharidosis Type IIIA (MPS IIIA) Enabling Receptor-Independent Brain Delivery (ASGCT 2026) - "Conclusion SYL-222 represents a groundbreaking, systemic single-dose therapy designed to deliver comprehensive treatment for MPS IIIA, addressing the disease at its core through a transformative approach. Meanwhile, our innovative SyLEC platform excels at transporting therapeutics precisely to challenging, hard-to-reach tissues and organs that traditional methods often fail to access effectively."

Gene therapy • CNS Disorders • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Rare Diseases

Treatment with UX111 Reduced Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) Exposure and Stabilized or Improved Functioning Across Dose, Age, and Stage of MPS IIIA (AAN 2026) - P2/3, P3 | "Conclusions UX111 showed a positive treatment effect and manageable safety across UX111 doses, age, and stage of disease at the time of treatment. LTFU continues with additional data forthcoming."

CNS Disorders • Lysosomal Storage Diseases

Ultragenyx BLA For UX111 Gene Therapy Accepted By FDA (RTTNews) - "The FDA set a Prescription Drug User Fee Act action date of September 19, 2026....The company said that during its prior late-cycle review, the FDA acknowledged the robustness of neurodevelopmental outcomes and noted that biomarker data provided additional supportive evidence."

FDA filing • PDUFA • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=9 | Not yet recruiting | Sponsor: Kevin Flanigan

New P1/2 trial • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=9 | Recruiting | Sponsor: Kevin Flanigan | Not yet recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: Abeona Therapeutics, Inc | N=16 ➔ 22 | Trial completion date: Dec 2020 ➔ Dec 2021

Enrollment change • Trial completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=36 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Active, not recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=36 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jan 2025 ➔ Jul 2027 | Trial primary completion date: Jan 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jun 2024 ➔ Jan 2025 | Trial primary completion date: Jun 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Phase classification: P1/2 ➔ P2/3 | Trial completion date: Dec 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Phase classification • Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: Abeona Therapeutics, Inc | Trial completion date: Dec 2022 ➔ Dec 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: Abeona Therapeutics, Inc | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2019 ➔ Dec 2022

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Ultragenyx Reports Third Quarter 2025 Financial Results and Corporate Update (GlobeNewswire) - "UX111 AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): expect to resubmit Biologics License Application (BLA) early in 2026....DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): BLA rolling submission underway, expect to complete in the fourth quarter of 2025."

FDA filing • Lysosomal Storage Diseases

Ultragenyx Receives Complete Response Letter from FDA for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA) (GlobeNewswire) - "Ultragenyx Pharmaceutical...announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for its Biologics License Application (BLA) for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA)....In the CRL, the FDA requested that the company provide additional information and improvements related to specific aspects of CMC and observations from the recently completed manufacturing facility inspections. The company believes that these observations are readily addressable, related to facilities and processes, and are not directly related to the quality of the product. The company will be working with the FDA over the next few months to resolve the observations. Once resolution is achieved, the company expects to resubmit the BLA and anticipates up to a 6-month review period to follow the resubmission."

CRL • Lysosomal Storage Diseases

Treatment with UX111 Gene Therapy Rapidly Reduced Heparan Sulfate (HS) Exposure in Cerebrospinal Fluid (CSF) and Improved Long-term Cognitive Function in Children with Mucopolysaccharidosis IIIA (MPS IIIA) (AAN 2025) - P1/2, P3 | "UX111 appears safe and effective in children with MPS IIIA leading to reduced CSF HS exposure and improved cognitive function."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Ultragenyx Announces FDA Acceptance and Priority Review of the Biologics License Application (BLA) for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA) (GlobeNewswire) - "Ultragenyx Pharmaceutical...announced the U.S. Food and Drug Administration (FDA or the Agency) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. The FDA also informed the company that they are not currently planning to hold an advisory committee meeting to discuss this application....The BLA submission for UX111 is supported by available data, including the latest data from the ongoing pivotal Transpher A and long-term follow-up studies presented at WORLDSymposium 2025..."

FDA filing • PDUFA • Priority review • Lysosomal Storage Diseases

An Integrated Process Characterization Approach to Enable Accelerated Commercialization Timeline of an Adeno-Associated Virus Based Treatment for Sanfilippo Syndrome (ASGCT 2024) - "Specifically, UX111 historical manufacturing data, UX111-specific PC data, and rAAV platform PC data are leveraged to generate the process and analytical control strategy (PACS) and to define PPQ ranges. The integrated PC approach not only provided a solid foundation to design a robust and reliable process, but also may enable the timely delivery of drug product to Sanfilippo syndrome patients in need."

Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Rare Diseases

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P3 | N=33 | Enrolling by invitation | Sponsor: Ultragenyx Pharmaceutical Inc | Phase classification: P=N/A ➔ P3 | N=50 ➔ 33 | Trial completion date: Dec 2026 ➔ Jun 2027

Enrollment change • Phase classification • Trial completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases