Abstract
Isaralgagene civaparvovec (ST-920) shows positive mean annualized eGFR slope in adults with Fabry disease: Topline results from the registrational phase 1/2 STAAR gene therapy study and long-term follow-up study
Molecular genetics and metabolism, Vol.147(2), 109334
02/2026
DOI: 10.1016/j.ymgme.2025.109334
Abstract
Introduction: An important therapeutic goal for Fabry disease (FD) is preservation of kidney function (e.g., estimated glomerular filtration rate [eGFR]). Approved treatments only stabilize or slow eGFR decline. Isaralgagene civaparvovec (hereafter ST-920) is an investigational gene therapy using a recombinant AAV2/6 vector containing human galactosidase alpha cDNA to produce continuous alpha-galactosidase A (α-Gal A) expression. We present updated results from Phase 1/2 STAAR study (NCT04046224) in adults with symptomatic FD and its follow-up study (NCT05039866). Method: STAAR was an open-label, single-dose, dose-ranging study, and enrolled participants who were either on enzyme replacement therapy (ERT), ERT pseudo-naïve (i.e., no ERT for ≥6 months) or ERT-naïve. A key efficacy objective was to assess ST-920 impact on renal function (eGFR). Participants were followed for 1-year and could enroll in ST-920-LT01 for long-term follow-up. Results: As of 10 April 2025 (data cut-off date), 33 participants (median age: 42 years [range: 18-67]) received ST-920 (up to 2.63 × 1013 vg/kg); median duration of follow-up was 24 months (range: 19 weeks-54 months). The elevated expression of α-Gal A and corresponding reduced plasma lyso-Gb3 levels were demonstrated. Improvements in renal function were observed in the 32 participants with 52-weeks follow-up, with a positive mean annualized eGFR slope of +1.965 mL/min/1.73 m2/year (95 % CI: −0.153, 4.083). Improvements in eGFR continued to be observed in participants (n = 19) with 2 years follow-up (+1.747 mL/min/1.73 m2/year [95 % CI: −0.106, 3.601]). As of the data cut-of date, all participants receiving ERT at baseline (n = 18) were able to discontinue ERT, with a median (SD) duration off ERT of 96.60 (46.56) weeks. ST-920 was well-tolerated with a favorable safety profile. Conclusions: ST-920 is a one-time, well-tolerated, durable treatment option for patients with FD that demonstrated a positive mean annualized eGFR slope, addressing an unmet medical need, and improvements in other patient outcomes.
Details
- Title: Subtitle
- Isaralgagene civaparvovec (ST-920) shows positive mean annualized eGFR slope in adults with Fabry disease: Topline results from the registrational phase 1/2 STAAR gene therapy study and long-term follow-up study
- Creators
- John A. Bernat - University of IowaRobert J. Hopkin - Cincinnati Children's Hospital Medical CenterWilliam R. Wilcox - Emory UniversityDerralynn Hughes - University College LondonJaya Ganesh - Icahn School of Medicine at Mount SinaiOzlem Goker-Alpan - Lysosomal and Rare Disorders Research and Treatment CenterKathleen Nicholls - The Royal Melbourne HospitalPatrick B. Deegan - Addenbrooke's HospitalLiching Cao - Sangamo BioSciences (United States)Michael Chen - Sangamo BioSciences (United States)Katharina H. Schreeb - Sangamo BioSciences (United States)
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.147(2), 109334
- DOI
- 10.1016/j.ymgme.2025.109334
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc; SAN DIEGO
- Language
- English
- Date published
- 02/2026
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9985139276202771
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