The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.


Among patients with Fabry disease previously treated with agalsidase alfa, switching to pegunigalsidase alfa was associated with improvement in renal function as measured by mean annualized estimated glomerular filtration rate (eGFR slope), according to study results presented at the 17th Annual WORLDSymposium.

Fabry disease is a rare genetic progressive disorder caused by deficient activity of the lysosomal α-galactosidase-A enzyme, which leads to progressive buildup of globotriaosylceramide (Gb3) in blood vessel walls throughout the body. Conditions resulting from Gb3 accumulation include chronic kidney disease, peripheral neuropathy, and cardiovascular disease, among others.

The open-label, switch-over phase 3 BRIDGE study evaluated the efficacy and safety of pegunigalsidase alfa, a plant cell-expressed recombinant, PEGylated, cross-linked α-galactosidase-A product candidate, in 22 adults (15 men, 7 women) with Fabry disease. The study included patients treated with agalsidase alfa for at least 2 years and on a stable dose (greater than 80% labelled dose/kg) for at least 6 months. Following a screening period, patients received intravenous infusions of pegunigalsidase alfa 1mg/kg every 2 weeks for 12 months.


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Among the 20 patients (13 men, 7 women) who completed the study, findings showed an improvement in mean annualized eGFR slope from a baseline of -5.90 to -1.2mL/min/1.73m2/year at 12 months. Male patients improved from -6.36 to -1.73mL/min/1.73m2/year and female patients improved from -5.03 to -0.21mL/min/1.73m2/year. After switching to pegunigalsidase alfa, a decrease in patients with progressing or fast progressing kidney disease was observed, and most patients achieved a stable status post-switch.

Treatment with pegunigalsidase alfa also reduced plasma globotriasylsphingosine (lysoGb3) mean concentrations by 31.5% from baseline (32.4% for male patients vs 29.8% for female patients).

As for safety, pegunigalsidase alfa was found to be well tolerated with all adverse events being transient in nature. There were 127 treatment-emergent adverse events (TEAEs) that occurred in 21 patients (95.5%); most TEAEs were mild or moderate in severity. Two patients withdrew from the study because of hypersensitivity reaction.

Patients who completed the study will continue to receive pegunigalsidase alfa in the long-term extension phase.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

  1. Linhart A, Dostalova G, Nicholls K, et al. Switching from agalsidase alfa to pegunigalsidase alfa to treat patients with Fabry disease: 1 year of treatment data from BRIDGE, a phase 3 open-label study. Presented at: 17th Annual WORLDSymposium; February 8-12, 2021. Abstract 141.
  2. Protalix BioTherapeutics and Chiesi Global Rare Diseases announce final results of BRIDGE phase III open-label, switch-over clinical trial evaluating pegunigalsidase alfa for the treatment of Fabry disease. [press release]. Carmiel, Israel and Boston, MA: Protalix BioTherapeutics, Inc.; December 30, 2020.