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Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study

2023; BioMed Central; Volume: 18; Issue: 1 Linguagem: Inglês

10.1186/s13023-023-02937-6

1750-1172

Aleš Linhart, Gabriela Dostálová, Kathy Nicholls, Michael L. West, Camilla Tøndel, Ana Jovanović, Pilar Giraldo, Bojan Vujkovac, Tarekegn Geberhiwot, Einat Brill‐Almon, Sari Alon, Raul Chertkoff, Rossana Rocco, Derralynn Hughes,

Trypanosoma species research and implications

Abstract 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 m 2 and plasma lyso-Gb 3 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 m 2 /year; 12 months post-switch, the mean eGFR slope was − 1.19 (1.77) mL/min/1.73 m 2 /year; and mean plasma lyso-Gb 3 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 m 2 /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.