Abstract
Isaralgagene civaparvovec (ST-920) gene therapy in adults with Fabry disease: Updated results from an ongoing phase 1/2 study (STAAR)
Molecular genetics and metabolism, Vol.144(2), 108773
02/2025
DOI: 10.1016/j.ymgme.2024.108773
Abstract
Background: Fabry disease (FD), is caused by mutations in the GLA gene, deficiency of alpha-galactosidase A (α-Gal-A), progressive accumulation of globotriaosylceramide (Gb3) and multi-organ dysfunction. Isaralgagene civaparvovec (ST-920) is an investigational gene therapy using a recombinant AAV2/6 vector containing human GLA cDNA to produce continuous, liver-specific α-Gal-A expression. Phase 1/2 study (STAAR; NCT04046224) evaluates ST-920 in adults with symptomatic FD. Methods: The primary endpoint is safety/tolerability; additional endpoints include α-Gal-A activity, plasma lyso-Gb3, eGFR slope, and quality of life. Results: As of a 29 Feb 2024 data cut, 31 patients have been dosed, 18 patients with >12-months follow-up. ST-920 up to a dose 2.63 × 1013 vg/kg was generally well tolerated, with no withdrawals due to AEs, no deaths and no Grade 4 AEs. Pyrexia, headache and fatigue were the most common AEs. Twenty six of 31 patients reached physiological or supraphysiological levels of alpha-Gal A at data cut, longest observations: 1100 days. By 13 Sept 2024, all ERT patients had successfully withdrawn from ERT. At Week 52, skin α-Gal A activity increased. Lyso-Gb3 levels dropped substantially in naïve/pseudo-naïve patients and slightly in ERT-treated patients before stabilizing. After ST-920 treatment, anti-drug antibodies (ADA) titers decreased markedly. Quality of life tools (FOS-MMSI, SF-36) showed statistically significant and clinically meaningful (> +3–5 point score) improvements. Vitality, reduction of pain and physical/general health increased in 18 patients with ≥12-months data and positive and statistically significant signals were observed for gastrointestinal symptoms. Conclusions: ST-920 seems to be a safe, well-tolerated option for FD patients. Results include increases in alpha-Gal A activity, reduction of plasma lyso-GB3, a positive immunogenicity profile and promising results for annualized eGFR slope and quality of life.
Details
- Title: Subtitle
- Isaralgagene civaparvovec (ST-920) gene therapy in adults with Fabry disease: Updated results from an ongoing phase 1/2 study (STAAR)
- Creators
- Derralynn Hughes - The Royal Free HospitalWilliam Wilcox - Emory University School of MedicineRobert J. Hopkin - Cincinnati Children's Hospital Medical CenterJaya Ganesh - Icahn School of Medicine at Mount SinaiJohn Bernat - University of IowaOzlem Goker-Alpan - Lysosomal and Rare Disorders Research and Treatment CenterKathy Nicholls - University of MelbournePatrick Deegan - Addenbrooke's HospitalMadeleine Pahl - University of California, IrvineChester B. Whitley - University of MinnesotaMichael Chen - Sangamo BioSciencesLiching Cao - Sangamo BioSciencesKatharina H. Schreeb - Sangamo BioSciences
- Resource Type
- Abstract
- Publication Details
- Molecular genetics and metabolism, Vol.144(2), 108773
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ymgme.2024.108773
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Medical Genetics and Genomics; Stead Family Department of Pediatrics
- Record Identifier
- 9984780239002771
Metrics
6 Record Views