Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease

Derralynn Hughes, Derlis Gonzalez, Gustavo Maegawa, John A. Bernat, Myrl Holida, Pilar Giraldo, Mohamed G. Atta, Raul Chertkoff, Sari Alon, Einat Brill Almon, Rossana Rocco, Ozlem Goker-Alpan

Research output: Contribution to journalArticlepeer-review


Purpose: Fabry disease (FD) is a rare lysosomal storage disorder caused by pathogenic variants in the GLA gene encoding α-galactosidase (α-Gal)-A. We evaluated long-term safety/efficacy of pegunigalsidase alfa, a novel PEGylated α-Gal-A enzyme replacement therapy (ERT) now approved for FD. Methods: In a phase-1/2 dose-ranging study, 15 ERT-naive adults with FD completed 12 months of pegunigalsidase alfa and enrolled in this 60-month open-label extension of 1 mg/kg pegunigalsidase alfa infusions every 2 weeks. Results: Fifteen patients enrolled (8 males; 7 females); 10 completed ≥48 months (60 months total treatment), and 2 completed 60 months (72 months total treatment). During treatment, most treatment-emergent adverse events were mild/moderate in severity and all infusion-related reactions were mild/moderate in severity. Four patients were transiently positive for anti-pegunigalsidase alfa IgG. Patients showed continuous reduction in plasma lyso-Gb3 concentrations with mean (standard error) reduction of 76.1 [25.1] ng/mL from baseline to month 24. At 60 months, the estimated glomerular filtration rate slope was comparable to that observed in patients treated with other ERTs. Cardiac function assessments revealed stability; no cardiac fibrosis was observed. Conclusion: In this first long-term assessment of pegunigalsidase alfa administration in patients with FD, we found favorable safety/efficacy. Our data suggest long-term continuous benefits of pegunigalsidase alfa treatment in adults with FD.

Original languageEnglish (US)
Article number100968
JournalGenetics in Medicine
Issue number12
StatePublished - Dec 2023


  • Anti-drug antibodies
  • Enzyme replacement therapy
  • Estimated glomerular filtration rate
  • Fabry disease
  • Pegunigalsidase alfa

ASJC Scopus subject areas

  • Genetics(clinical)


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