2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Long-Term Safety and Efficacy of Pegunigalsidase Alfa Administered Every 4 Weeks in Fabry Disease: 2-Year Interim Results from BRIGHT51

Long-Term Safety and Efficacy of Pegunigalsidase Alfa Administered Every 4 Weeks in Fabry Disease: 2-Year Interim Results from BRIGHT51

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This study presented the 2-year interim results from the BRIGHT51 study, which evaluated the long-term safety and efficacy of pegunigalsidase alfa in adults with Fabry disease. Pegunigalsidase alfa, a PEGylated recombinant alpha-galactosidase-A enzyme, has an extended half-life compared to current enzyme replacement therapies (ERTs) for Fabry disease.<br /><br />The study enrolled 30 adults with Fabry disease who had previously received agalsidase alfa or agalsidase beta every 2 weeks. The patients were switched to pegunigalsidase alfa administered at a dose of 2 mg/kg every 4 weeks. At the interim analysis, 29 out of 30 patients completed the study and were currently undergoing treatment in the BRIGHT51 study.<br /><br />The main findings of the study were as follows:<br /><br />1. Safety: The switch to pegunigalsidase alfa had a favorable safety profile, with no patients developing de novo antidrug antibodies (ADAs) and no serious treatment-related adverse events. All treatment-related adverse events were mild to moderate in severity.<br /><br />2. ADAs: Only patients with pre-existing IgG antibodies tested positive for ADAs to pegunigalsidase alfa during the study. The proportion of patients positive for ADAs decreased over time, and all patients tested negative for antibodies to the plant glycans or PEG moieties of pegunigalsidase alfa.<br /><br />3. Efficacy: Plasma lyso-Gb3 concentrations remained relatively stable throughout the study. Most patients had a change of less than 10 nM in plasma lyso-Gb3 concentration at Week 108. The mean estimated glomerular filtration rate (eGFR) had a decline of -5.10 mL/min/1.73m2 from baseline at Week 108. Patients with pre-existing ADAs had a more negative eGFR slope, indicating a potential impact on the rate of eGFR decline.<br /><br />The authors concluded that the long-term administration of pegunigalsidase alfa every 4 weeks is safe and effective in adults with Fabry disease. The switch from previous ERTs to pegunigalsidase alfa resulted in a favorable safety profile and a reduction in treatment burden for patients. The ongoing BRIGHT51 extension study will further evaluate the long-term safety and efficacy of pegunigalsidase alfa in Fabry disease.

Asset Subtitle

Submitter Only - Adam Bijou, MD; Presenting Author - John A. Bernat, MD, PhD; Co-Author - Myrl Holida, PA-C; Co-Author - Nicola Longo, MD PhD FACMG; Co-Author - Ozlem Goker-Alpan, MD; Co-Author - Eric Wallace, MD; Co-Author - Patrick Deegan, MD; Co-Author - Camilla Tondel, MD PhD; Co-Author - Francois Eyskens, MD, PhD; Co-Author - Ulla Feldt-Rasmussen, MD, DMSc; Co-Author - Derralynn Hughes, MA DPhil FRCP FRCPath; Co-Author - Antonio Pisani, MD; Co-Author - Ales Linhart, MD, DSc; Co-Author - Rossana Rocco, MD; Co-Author - Einat Almon, PhD; Co-Author - Sari Alon, MD; Co-Author - Raul Chertkoff, MD; Co-Author - David G. Warnock, MD; Co-Author - Stephen Waldek, MD, PhD; Co-Author - William R. Wilcox, MD, PhD, FACMG;

Meta Tag

Enzyme Replacement Therapy

Lysosomal Diseases

Metabolic Disorder

Therapy

X-Inactivation/X-Linked Disease

Co-Author Myrl Holida, PA-C

Co-Author Nicola Longo, MD PhD FACMG

Co-Author Ozlem Goker-Alpan, MD

Co-Author Eric Wallace, MD

Co-Author Patrick Deegan, MD

Co-Author Camilla Tondel, MD PhD

Co-Author Francois Eyskens, MD, PhD

Co-Author Ulla Feldt-Rasmussen, MD, DMSc

Co-Author Derralynn Hughes, MA DPhil FRCP FRCPath

Co-Author Antonio Pisani, MD

Co-Author Ales Linhart, MD, DSc

Co-Author Rossana Rocco, MD

Co-Author Einat Almon, PhD

Co-Author Sari Alon, MD

Co-Author Raul Chertkoff, MD

Co-Author David G. Warnock, MD

Co-Author Stephen Waldek, MD, PhD

Co-Author William R. Wilcox, MD, PhD, FACMG

Presenting Author John A. Bernat, MD, PhD

Submitter Only Adam Bijou, MD

Keywords

BRIGHT51 study

pegunigalsidase alfa

Fabry disease

long-term safety

long-term efficacy

enzyme replacement therapies

ADAs

plasma lyso-Gb3 concentrations

glomerular filtration rate

treatment burden