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.
Orphanet J Rare Dis
; 18(1): 332, 2023 Oct 21.
Article
em En
| MEDLINE
| ID: mdl-37865771
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 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Fabry
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Orphanet J Rare Dis
Assunto da revista:
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
República Tcheca