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Background <p>Enzyme replacement therapies (ERTs) approved for Fabry disease require infusions every 2 weeks (E2W). Pegunigalsidase alfa, a PEGylated ERT with a prolonged half-life vs. other ERTs, may allow extension of the dosing interval to every 4 weeks (E4W). </p> <p>BRIGHT F51 (NCT03614234) is an ongoing phase III, open-label extension study evaluating long-term efficacy and safety of pegunigalsidase alfa 2 mg/kg E4W in adults with Fabry disease previously treated with agalsidase alfa or beta E2W for ≥ 3 years who completed one year of pegunigalsidase alfa treatment in the BRIGHT study. This interim analysis reports results following 3–5 years of treatment (cutoff date December 31, 2022).</p> Results <p>Twenty-nine patients were enrolled. Median (interquartile range [IQR]) annualized eGFR slope during treatment was ‒2.2 (‒2.9; ‒1.1) mL/min/1.73 m<sup>2</sup>/year (males: ‒2.4 [‒2.9; ‒1.0, <i>n = </i>23]; females: ‒1.8 [‒2.4; ‒1.3, <i>n </i>= 6]; anti-drug antibody [ADA]-positive: ‒2.6 [‒4.0; ‒1.7, <i>n =</i> 9 all male]; ADA-negative: ‒1.8 [‒2.7; ‒0.6, <i>n = </i>20]). Median (IQR) change in plasma lyso-Gb3 from baseline to Week 208 was 3.2 (‒3.9; 8.5, <i>n = </i>17) nM in males; concentrations remained low and stable in females. Overall, 51/477 treatment-emergent adverse events in 13 patients (45%) were considered treatment-related (all mild/moderate). Nine patients (31%) experienced mild/moderate infusion-related reactions. One patient developed transient <i>de novo </i>ADAs.</p> Conclusions <p>Long-term treatment with pegunigalsidase alfa 2 mg/kg E4W was well-tolerated and maintained disease stability, especially in females and ADA-negative males; more data are needed to better understand outcomes in ADA-positive males. Clinical outcomes should be closely monitored during E4W treatment. The final results of this extension study will further assess the feasibility of this dosing regimen.</p> Trial registration details <p>ClinicalTrials.gov, NCT03614234. Registered July 30, 2018; <a href="https://clinicaltrials.gov/study/NCT03614234">https://clinicaltrials.gov/study/NCT03614234</a>.</p> Graphical Abstract <p></p>

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Long-term efficacy and safety of pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease: results from up to 5 years of the BRIGHT F51 phase III, open-label extension study

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  • 发表日期：

    2026年3月20日

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  • Myrl Holida,
  • Aleš Linhart,
  • Nicola Longo,
  • Eric Wallace,
  • Camilla Tøndel,
  • Derralynn Hughes,
  • David G. Warnock,
  • Antonio Pisani,
  • François Eyskens,
  • Patrick Deegan,
  • Ulla Feldt-Rasmussen,
  • Ozlem Goker-Alpan,
  • Ankit Mehta,
  • Giovanni Piotti,
  • Vito Fichera,
  • Meng Wang,
  • Raul Chertkoff,
  • Stephen Waldek,
  • William R. Wilcox,
  • John A. Bernat

摘要

Background

Enzyme replacement therapies (ERTs) approved for Fabry disease require infusions every 2 weeks (E2W). Pegunigalsidase alfa, a PEGylated ERT with a prolonged half-life vs. other ERTs, may allow extension of the dosing interval to every 4 weeks (E4W).

BRIGHT F51 (NCT03614234) is an ongoing phase III, open-label extension study evaluating long-term efficacy and safety of pegunigalsidase alfa 2 mg/kg E4W in adults with Fabry disease previously treated with agalsidase alfa or beta E2W for ≥ 3 years who completed one year of pegunigalsidase alfa treatment in the BRIGHT study. This interim analysis reports results following 3–5 years of treatment (cutoff date December 31, 2022).

Results

Twenty-nine patients were enrolled. Median (interquartile range [IQR]) annualized eGFR slope during treatment was ‒2.2 (‒2.9; ‒1.1) mL/min/1.73 m2/year (males: ‒2.4 [‒2.9; ‒1.0, n = 23]; females: ‒1.8 [‒2.4; ‒1.3, n = 6]; anti-drug antibody [ADA]-positive: ‒2.6 [‒4.0; ‒1.7, n = 9 all male]; ADA-negative: ‒1.8 [‒2.7; ‒0.6, n = 20]). Median (IQR) change in plasma lyso-Gb3 from baseline to Week 208 was 3.2 (‒3.9; 8.5, n = 17) nM in males; concentrations remained low and stable in females. Overall, 51/477 treatment-emergent adverse events in 13 patients (45%) were considered treatment-related (all mild/moderate). Nine patients (31%) experienced mild/moderate infusion-related reactions. One patient developed transient de novo ADAs.

Conclusions

Long-term treatment with pegunigalsidase alfa 2 mg/kg E4W was well-tolerated and maintained disease stability, especially in females and ADA-negative males; more data are needed to better understand outcomes in ADA-positive males. Clinical outcomes should be closely monitored during E4W treatment. The final results of this extension study will further assess the feasibility of this dosing regimen.

Trial registration details

ClinicalTrials.gov, NCT03614234. Registered July 30, 2018; https://clinicaltrials.gov/study/NCT03614234.

Graphical Abstract