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Abstract: PO1938

Reduction of Globotriaosylceramide Inclusions in Renal Peritubular Capillaries in Patients with Fabry Disease Following Treatment with Pegunigalsidase Alfa

Session Information

Category: Pathology and Lab Medicine

  • 1600 Pathology and Lab Medicine


  • Barisoni, Laura, Duke University School of Medicine, Durham, North Carolina, United States
  • Jennette, J. Charles, University of North Carolina System, Chapel Hill, North Carolina, United States
  • Holida, Myrl D., The University of Iowa Healthcare, Iowa City, Iowa, United States
  • Goker-Alpan, Ozlem, Lysosomal Disorders Research and Treatment Unit, Fairfax, Virginia, United States
  • Maegawa, Gustavo, University of Florida, Gainesville, Florida, United States
  • Giraldo, Pilar, Hospital de Dia Quiron, Zaragoza, Spain
  • Gonzalez, Derlis Emilio, Instituto Privado del Nino y Adolescente, Asuncion, Gran Asunción, Paraguay
  • Tuffaha, Ahmad M., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Alon, Sari, Protalix Biotherapeutics, Carmiel, Northern, Israel
  • Almon, Einat, Protalix Biotherapeutics, Carmiel, Northern, Israel
  • Chertkoff, Raul, Protalix Biotherapeutics, Carmiel, Northern, Israel
  • Hughes, Derralynn, Royal Free London NHS Foundation Trust, London, London, United Kingdom

Fabry disease (FD) is a rare genetic disorder characterized by reduced activity of the lysosomal enzyme α-galactosidase A (α-Gal A), leading to accumulation of sphingolipids such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3), and organ dysfunction. Gb3 inclusions form in various renal cell types and Gb3 clearance from renal peritubular capillaries (PTCs) has been used as a surrogate endpoint in trials of approved FD therapies. The objective of this analysis was to quantify the reduced burden of Gb3 inclusions in PTCs in patients with FD participating in a phase 1/2 trial of pegunigalsidase alfa (recombinant α-Gal A) enzyme replacement therapy.


In a phase 1/2 dose-ranging study (NCT01678898), 18 adults with FD received 0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of pegunigalsidase alfa by intravenous infusion every 2 weeks for up to 12 months. Kidney biopsies were taken at baseline and after 6 months of treatment. Levels of Gb3 inclusions in renal PTCs were determined using the Barisoni Lipid Inclusions Scoring System (BLISS) protocol (Barisoni L et al. Arch Pathol Lab Med. 2012;136:816–824).


Of 14 evaluable patients with available kidney biopsies at baseline and 6 months, 12 patients (85.7%) had ≥20% reduction, 11 patients (78.6%) had ≥50% reduction, and 3 patients (21.4%) had ≥90% reduction in Gb3 inclusions. In the analysis (n=13; excluding 1 male patient due to minimal renal involvement), the mean BLISS score 6 months from baseline was lowered for all doses (reduced by 75.5%, 86.5%, and 39.5% in the 0.2 mg/kg, 1.0 mg/kg, and 2.0 mg/kg treatment groups, respectively). The magnitude of reduction of Gb3 inclusions was greater in males (n=7; reduction: 85.0%) vs females (n=6; reduction: 47.7%). Overall, mean BLISS score was reduced from 4.23 at baseline to 0.83 at 6 months (67.8% ± 8.9%). Reduction in Gb3 inclusions at 6 months was correlated with a reduction in plasma lysoGb3 at 12 months (R=0.905).


Results from this phase 1/2 study demonstrated that pegunigalsidase alfa reached the affected tissue and effectively reduced the number of Gb3 inclusions in renal PTCs at 6 months in adults with FD.