Kidney Week

Abstract: FR-PO704

Kidney Function and Isolated Kidney Transplant Outcomes in Primary Hyperoxaluria Type 1 Treated with Long-Term Lumasiran

Session Information

• Pediatric Nephrology - 1
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

• Somers, Michael J., Division of Pediatric Nephrology, Boston Children’s Hospital, Boston, Massachusetts, United States

Michael J. Somers, MD

• Devresse, Arnaud, Department of Nephrology, Cliniques Universitaires, Brussels, Belgium

Arnaud Devresse

• Willey, Richard G., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Richard G. Willey, MS

• Murphy, Michael Desmond, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Michael Desmond Murphy, PharmD, RPh

• Sellier-Leclerc, Anne-Laure All, Division of Pediatric Nephrology-Rheumatology, Hôpital Femme-Mère-Enfant, Lyon, France

Anne-Laure All Sellier-Leclerc, MD

• Kaspar, Cristin, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Cristin Kaspar, MD, MS

• Bacchetta, Justine, Lyon Est Medical School, Hospices Civils de Lyon, Lyon, France

Justine Bacchetta, MD, PhD

Background

Primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder associated with hepatic oxalate overproduction, leads to progressive kidney damage. Prior to availability of the RNA interference therapeutic lumasiran, reported graft survival rates after isolated kidney transplantation (iKT) in PH1 patients (pts) were poor: 54% at 3 months (M) and 46% at 1 year (y). Phase 2 (NCT03350451) and 3 Phase 3 trials (ILLUMINATE-A, NCT03681184; ILLUMINATE-B, NCT03905694; and ILLUMINATE-C, NCT04152200) have shown sustained urinary oxalate and plasma oxalate (POx) reduction and acceptable safety with lumasiran across a wide range of ages and baseline (BL) kidney function. Long-term follow-up allows evaluation of native kidney survival and iKT outcomes in lumasiran-treated pts.

Methods

Descriptive kidney function data from lumasiran clinical trials and post-transplant outcomes in pts following iKT were compiled.

Results

Mean annual rates of eGFR change (mL/min/1.73m²/y) were –0.6 over 48 M in the Phase 2 trial (N=20), –1.2 over 48 M in ILLUMINATE-A (N=35), and –0.8 over 30 M of follow-up in ILLUMINATE-B (N=15). The range of BL eGFR values was 32–174 mL/min/1.73m² in these 3 trials. ILLUMINATE-C enrolled PH1 pts with advanced kidney disease; pts were assigned to Cohort A (not on hemodialysis [HD]) or Cohort B (on HD). Three pts in Cohort A, who had the lowest BL eGFR (8.6–16.5 mL/min/1.73m²), required HD before the M36 data cutoff; the other 2 remaining Cohort A pts (BL eGFR 24.0, 34.1 mL/min/1.73m²) had annual rates of eGFR decline of –2.3 and –0.9 mL/min/1.73m²/y, respectively, over 36 M. Five Cohort B pts underwent iKT as of M36. All 5 had POx reduction from BL prior to transplantation, and further reduction post-transplant indicating improved POx clearance with functioning kidney grafts. No patients experienced oxalate nephropathy post-transplantation. All 5 remained HD-free and continued lumasiran treatment post-transplant as of M36.

Conclusion

Lumasiran treatment for PH1 resulted in minimal annual eGFR decline over 30 to 60 M in pts with BL CKD stages 1–4, and effectively lowered POx to allow for iKT, rather than liver-kidney transplantation, in some pts with end-stage kidney disease.

Funding

• Commercial Support – Alnylam Pharmaceuticals