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 –