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Long-term safety and efficacy of pegunigalsidase alfa in patients with Fabry disease: Results from the phase III BRILLIANCE extension study
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Long-term safety and efficacy of pegunigalsidase alfa in patients with Fabry disease: Results from the phase III BRILLIANCE extension study

John Bernat, Aleš Linhart, Ozlem Goker-Alpan, Shoshi Tessler, Meng Wang, Giovanni Piotti, Joana Almeida and Derralynn Hughes
Molecular genetics and metabolism, Vol.147(2), 109335
02/2026
DOI: 10.1016/j.ymgme.2025.109335

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Abstract

BRILLIANCE (NCT03566017; last patient/last visit 21-January-2025) is an international, single-arm, open-label Phase 3 extension study characterizing the long-term safety/efficacy profile of pegunigalsidase alfa 1 mg/kg every 2 weeks (E2W) in adults with Fabry disease (FD). Eligible patients had either completed the Phase 3 BRIDGE or BALANCE trials, or ≥ 48 months of the phase 1/2 PB-102-F03 trial. On enrollment to BRILLIANCE, patients continued receiving, or switched to, pegunigalsidase alfa (PA) 1 mg/kg; baseline was defined as last assessment prior to the first ever PA infusion. Ninety-seven patients were enrolled; 54.6 % had classic FD, 61.9 % were male. At baseline, most patients had received enzyme replacement therapy (71.1 % agalsidase beta; 18.6 % agalsidase alfa); 25.8 % had anti-drug antibodies (ADAs) against PA, and median (range) baseline estimated glomerular filtration rate (eGFR) was 77.7 (24.4, 131.0) mL/min/1.73 m2. From first dose, cumulative population and median (range) patient-level exposure to PA were 529.1 years and 5.7 (1.3, 10.6) years, respectively. Treatment-related adverse events (TRAEs) occurred in 47.4 % of patients, representing only 5.4 % of all adverse events (n = 134/2486). Serious TRAEs were rare (n = 2; 2.1 %, both infusion-related reactions [IRRs]), and only one patient (1.0 %) discontinued due to a non-serious TRAE. IRRs were infrequent (0.6/100 infusions; 83 IRRs in 29 [29.9 %] patients <24 h post-infusion), with no withdrawals or deaths attributed to IRRs. Four deaths occurred, all unrelated to PA. Kidney function remained stable throughout the study (median [range] annualized eGFR slope − 1.77 [−21.2, 4.2] mL/min/1.73 m2/year) and low plasma globotriaosylsphingosine (lyso-Gb3) levels were maintained without re-accumulation. The proportion of ADA-positive patients remained consistent from baseline to the last visit (24.7 %). These findings demonstrate that long-term treatment with pegunigalsidase alfa 1 mg/kg E2W offers a sustained safety and efficacy profile in adults with FD over a median of nearly six years, supporting its role as a viable long-term therapy.

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