Kidney Week

Abstract: FR-PO231

Pharmacokinetic (PK) Results From a Phase 3 Trial to Evaluate Pegunigalsidase Alfa Every 4 Weeks (Q4W) in Patients (Pts) With Fabry Disease Previously Treated With Agalsidase Beta or Agalsidase Alfa

Session Information

• Pharmacology
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

• 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

Authors

• Tøndel, Camilla, Haukeland Universitetssjukehus, Bergen, Norway

Camilla Tøndel,

• Wallace, Eric L., University of Alabama, Birmingham, Alabama, United States

Eric L. Wallace,

• Rocco, Rossana, Chiesi Farmaceutici S.p.A., Parma, Italy

Rossana Rocco,

• Almon, Einat, Protalix Biotherapeutics, Carmiel, Northern, Israel

Einat Almon,

• Alon, Sari, Protalix Biotherapeutics, Carmiel, Northern, Israel

Sari Alon,

• Blinder-Haddad, Liora, Protalix Biotherapeutics, Carmiel, Northern, Israel

Liora Blinder-Haddad,

• Chertkoff, Raul, Protalix Biotherapeutics, Carmiel, Northern, Israel

Raul Chertkoff,

• Warnock, David G., University of Alabama, Birmingham, Alabama, United States

David G. Warnock,

• Waldek, Stephen, University of Sunderland, Sunderland, United Kingdom

Stephen Waldek,

• Pisani, Antonio, University Federico II of Naples, Naples, Italy

Antonio Pisani,

Background

Fabry disease is a lysosomal storage disease caused by X-linked deficiency of alfa-galactosidase-A. Two enzyme replacement therapies (ERTs) are approved for Fabry disease (agalsidase alfa and agalsidase beta) with infusion every 2 wks. We present PK results from a phase 3 trial of pegunigalsidase alfa administered Q4W to pts with Fabry disease previously treated with ERTs.

Methods

In this phase 3, open-label, switch-over study, pts aged 18–60y with Fabry disease who had received ERTs for ≥3y (with stable dose for ≥6mo) and had estimated glomerular filtration rate ≥30mL/min/1.73 m² received IV infusion of pegunigalsidase alfa 2.0mg/kg Q4W for 52 wks. Blood samples for PK assessment were collected on Day 1 and at Wk 52 at 13 timepoints.

Results

30 pts (24 male, 6 female) enrolled; 29 completed the study and entered the open-label extension (OLE) study. Main PK parameters are shown (Table). From baseline to week 52, pegunigalsidase alfa had a mean C_max ranging from 35 876.7–46 829.6ng/mL, with t_max near end of infusion time, and mean t_1/2 ranging from 100–134h. Detectable pegunigalsidase alfa concentrations after each 4-wk dosing interval were above the lower limit of quantitation (19.5ng/mL), ranging from 167.0–301.5ng/mL. Pts with antidrug antibodies (ADAs) at baseline (n=10) had lower AUC_0-last (1 047 637h●ng/mL) and shorter t_1/2 (41.0h; range: 1.1–136.3h) after 1st infusion and throughout the study vs the overall population.

Conclusion

Mean pegunigalsidase alfa concentration at the end of each dosing interval supported Q4W dosing. Long-term clinical outcomes with Q4W dosing are being assessed in the OLE.

Funding

• Commercial Support – This study was sponsored by Protalix. Medical writing support was provided by Chris Kirk, PhD, on behalf of Oxford PharmaGenesis Inc., Newtown, PA, and funded by Chiesi Inc. The investigators would like to acknowledge the study participants and their caregivers for participating in this study.