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. 2023 Oct 21;18(1):332.
doi: 10.1186/s13023-023-02937-6.

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

Aleš Linhart  1 , Gabriela Dostálová  2 , Kathy Nicholls  3 , Michael L West  4 , Camilla Tøndel  5   6 , Ana Jovanovic  7 , Pilar Giraldo  8 , Bojan Vujkovac  9 , Tarekegn Geberhiwot  10 , Einat Brill-Almon  11 , Sari Alon  11 , Raul Chertkoff  11 , Rossana Rocco  12 , Derralynn Hughes  13
Affiliations

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

Aleš Linhart et al. Orphanet J Rare Dis. .

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.

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Conflict of interest statement

AL: Received speakers’ fees and consultancy honoraria from Chiesi, Sanofi-Genzyme, Takeda, Avrobio, and Alnylam. GD: Received speakers’ fees and consultancy honoraria from Sanofi, Takeda, Amicus, Chiesi, Greenovation Biotech GmbH. KN: Received grants and personal fees from Sanofi-Genzyme, Takeda; personal fees from Amicus, Idorsia, and Protalix. MW: Received research grants, honoraria, and/or consultant fees from Takeda, Sanofi-Genzyme, Amicus, Protalix, and Idorsia. Dr. West owns IP related to cardiac biomarkers and gene therapy in Fabry disease. CT: Received consultancy honoraria from Sanofi Genzyme, Amicus Therapeutics, Chiesi, and Acelink; participated in studies supported by Sanofi Genzyme, Shire, Protalix, Chiesi, Freeline, and Idorsia. AJ: Received grants from Amicus; honoraria and travel and accommodation from Takeda, Amicus, and Sanofi-Genzyme. PG: The author declares no competing interests. BV: Received speakers’ fees and consultancy honoraria from Sanofi-Genzyme, Takeda, Amicus, Chiesi, and Greenovation Biotech. TG: The author declares no competing interests. EB: Employed by Protalix. SA: Employed by Protalix. RC: Former full-time employee of Protalix Biotherapeutics and current consultant to Protalix Biotherapeutics and Chiesi USA, Inc. RR: Full-time employee of Chiesi Farmaceutici S.p.A. DH: Received honoraria for speaking and advisory boards from Amicus, Takeda, Sanofi-Genzyme, Freeline, and Protalix. Honoraria are administered through UCL consultants and are used in part to support laboratory research.

Figures

Fig. 1
Fig. 1
Change in plasma lyso-Gb3 in males and females (efficacy population). Anti-pegunigalsidase alfa ADA assessment was conducted at baseline, Weeks 4, 8, 12, 16, 20, 26, 38, and 52; positive status is shown with an x. ADA, antidrug antibody
Fig. 2
Fig. 2
eGFR annualized slope in males, females, and overall study population (efficacy population). eGFR estimated glomerular filtration rate, SE standard error
Fig. 3
Fig. 3
Kidney disease severity status (eGFR slope) shift from pre-switch to post-switch (efficacy population). Fast-progressing: eGFR slope <  − 5 mL/min/1.73 m2/year [4]. Progressing: eGFR slope ≥  − 5 to <  − 3 mL/min/1.73 m2/year. Stable: eGFR slope ≥  − 3 mL/min/1.73 m2/year. eGFR estimated glomerular filtration rate
See this image and copyright information in PMC

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