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.

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.

• Authors: Aleš Linhart, Gabriela Dostálová, Kathy Nicholls, Michael L West, Camilla Tøndel, Ana Jovanovic, Pilar Giraldo, Bojan Vujkovac, Tarekegn Geberhiwot, Einat Brill-Almon, Sari Alon, Raul Chertkoff, Rossana Rocco, Derralynn Hughes
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 18 Issue 1 Pg. 332 (Oct 21 2023) ISSN: 1750-1172 [Electronic] England
• PMID: 37865771 (Publication Type: Journal Article)
• Copyright: © 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).

Chemical References

• agalsidase alfa
• alpha-Galactosidase
• Isoenzymes
• Antibodies
• Recombinant Proteins

Topics

• Adult
• Male
• Humans
• Female
• Fabry Disease (drug therapy)
• alpha-Galactosidase (therapeutic use)
• Isoenzymes (adverse effects)
• Treatment Outcome
• Antibodies (therapeutic use)
• Enzyme Replacement Therapy (methods)
• Recombinant Proteins (therapeutic use)