BACKGROUND: Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD). OBJECTIVE/METHODS: BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years. RESULTS: Twenty-seven patients were screened; 22 met eligibility criteria; and 20 (13 men, 7 women) completed the study. Pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events (TEAEs) being of mild or moderate severity. The incidence of treatment-related TEAEs was low, with 2 (9%) discontinuations due to TEAEs. Five patients (23%) reported infusion-related reactions. Overall mean (SD; n = 22) baseline estimated glomerular filtration rate (eGFR) was 82.5 (23.4) mL/min/1.73 m2 and plasma lyso-Gb3 level was 38.3 (41.2) nmol/L (men: 49.7 [45.8] nmol/L; women: 13.8 [6.1] nmol/L). Before switching to pegunigalsidase alfa, mean (standard error [SE]) annualized eGFR slope was - 5.90 (1.34) mL/min/1.73 m2/year; 12 months post-switch, the mean eGFR slope was - 1.19 (1.77) mL/min/1.73 m2/year; and mean plasma lyso-Gb3 reduced by 31%. Seven (35%) out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline. Mean (SE) changes in eGFR slope for ADA-positive and ADA-negative patients were + 5.47 (3.03) and + 4.29 (3.15) mL/min/1.73 m2/year, respectively, suggesting no negative impact of anti-pegunigalsidase alfa ADAs on eGFR slope. CONCLUSION: Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with agalsidase alfa. TRN: NCT03018730. Date of registration: January 2017.

2nd Department of Internal Cardiovascular Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague U Nemocnice 2 128 08 Prague 2 Czech Republic

Centro de Investigación Biomédica en Red de Enfermedades Raras Hospital de Dia Quiron Zaragoza Spain

Chiesi Farmaceutici S p A Parma Italy

Department of Clinical Science University of Bergen Bergen Norway

Department of Diabetes Endocrinology and Metabolism University Hospitals Birmingham NHS Foundation Trust and University of Birmingham Birmingham England UK

Department of Inherited Metabolic Disease Salford Royal Salford England UK

Department of Internal Medicine General Hospital Slovenj Gradec Slovenj Gradec Slovenia

Department of Nephrology Royal Melbourne Hospital and The University of Melbourne Parkville Australia

Division of Nephrology Department of Medicine Dalhousie University Halifax NS Canada

Lysosomal Storage Disorders Unit Royal Free London NHS Foundation Trust and University College London London England UK

Nephrology and Rheumatology Unit Department of Pediatrics Haukeland University Hospital Bergen Norway

Protalix Biotherapeutics Carmiel Israel

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A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies

Pegunigalsidase alfa: a novel, pegylated recombinant alpha-galactosidase enzyme for the treatment of Fabry disease

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ClinicalTrials.gov
NCT03018730