Kidney Week

Abstract: TH-PO0907

Long-Term Lumasiran Treatment, Kidney Function, and Isolated Kidney Transplant Outcomes in Primary Hyperoxaluria Type 1

Session Information

• Transplantation: Clinical - Glomerular Diseases, Infections, and Rejection
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2102 Transplantation: Clinical

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 Saint-Luc, Brussels, Belgium

Arnaud Devresse

• Du, Weiming, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Weiming Du, MS

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

Michael Desmond Murphy, PharmD, RPh

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

Cristin Kaspar, MD, MS

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

Anne-Laure All Sellier-Leclerc, MD

• 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 kidney failure, with poor historical graft survival rates after isolated kidney transplantation (iKT). A Phase 2 (NCT03350451) and 3 Phase 3 trials (ILLUMINATE-A, NCT03681184; ILLUMINATE-B, NCT03905694; ILLUMINATE-C, NCT04152200) showed sustained urinary oxalate and plasma oxalate (POx) reduction and acceptable safety with the RNA interference therapeutic lumasiran. Long-term follow-up allows for evaluation of native kidney survival and iKT outcomes in lumasiran-treated patients.

Methods

Kidney function (eGFR) change for eligible patients age ≥12 months and post-iKT outcomes were characterized.

Results

Regression-estimated mean annual rates of eGFR change (slope [SEM] mL/min/1.73m²/year [Y]) were −0.4 (1.0) over 54 months (M) in the Phase 2 trial (N=20; ages 6-43 Y), −0.6 (0.7) over 60 M in ILLUMINATE-A (N=39; ages 6-60 Y), and 0.3 (0.8) over 60 M in ILLUMINATE-B (N=18; ages 3-72 M). Baseline eGFR ranged from 32 to 174 mL/min/1.73m². ILLUMINATE-C enrolled PH1 patients with advanced kidney disease, assigned to Cohort A (not on hemodialysis; n=6) or Cohort B (on hemodialysis; n=15). Three patients in Cohort A, whose baseline eGFR ranged from 8.6 to 16.5 mL/min/1.73m², required dialysis before M36. Three Cohort A patients remained off dialysis through M36; 2 patients had mean annual rates of eGFR decline of −2.3 and −0.9 mL/min/1.73m²/Y, and 1 patient had evaluable eGFR (age >12 months) starting at M8, which steadily improved from 37.1 to 54.3 mL/min/1.73m² (M8 and M36, respectively). All 5 Cohort B patients who underwent iKT as of M36 had POx reduction from baseline prior to transplantation and further reduction post-iKT, indicating improved POx clearance with functioning grafts. None experienced oxalate nephropathy after iKT. With 3 to 29 M of post-iKT follow-up as of M36, all 5 remained dialysis-free and continued lumasiran treatment.

Conclusion

Long-term lumasiran treatment resulted in minimal annual eGFR decline over 54 to 60 M in patients (baseline ages 3 M-60 Y) with PH1, in whom eGFR decline is expected, and effectively lowered POx to allow for iKT in some patients with end-stage kidney disease.

Funding

• Commercial Support – Alnylam Pharmaceuticals

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025s2f1zxga