Kidney Week

Abstract: SA-PO0709

Final 60-Month Efficacy, Safety, and Kidney Stone Outcomes of a Phase 3 Trial of Lumasiran for Primary Hyperoxaluria Type 1 in Infants and Young Children

Session Information

• Pediatric Nephrology: Transplantation, Hypertension, AKI, Genetics, and Developmental Diseases
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

• Sas, David J., Mayo Clinic, Rochester, Minnesota, United States

David J. Sas, DO, MPH

• Michael, Mini, Texas Children’s Hospital, Houston, Texas, United States

Mini Michael, MD, FASN

• Frishberg, Yaacov, Shaare Zedek Medical Center, Jerusalem, Israel

Yaacov Frishberg, MD

• Hayes, Wesley Nathan, Great Ormond Street Hospital for Children NHS, London, United Kingdom

Wesley Nathan Hayes, MBChB

• Benshalom, Efrat, Shaare Zedek Medical Center, Jerusalem, Israel

Efrat Benshalom, MD

• Shasha-Lavsky, Hadas, Galilee Medical Center, Nahariya, Israel

Hadas Shasha-Lavsky, MD

• Sellier-Leclerc, Anne-Laure All, Hôpital Femme Mère Enfant, Bron, France

Anne-Laure All Sellier-Leclerc, MD

• Hogan, Julien, Robert Debré Hospital, APHP, Paris, France

Julien Hogan

• 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

• Magen, Daniella, Pediatric Nephrology Institute, Haifa, Israel

Daniella Magen, MD

Group or Team Name

• On behalf of the ILLUMINATE-B Study Investigators.

Background

Primary hyperoxaluria type 1 (PH1) is a genetic disease of oxalate overproduction leading to urolithiasis, nephrocalcinosis (NC), and systemic oxalosis. Lumasiran is the first liver-directed RNA interference therapeutic for PH1 administered to infants and children age ≤6 years. We present final efficacy and safety results through Month (M) 60 of ILLUMINATE-B (NCT03905694), including outcomes in patients (pts) who had kidney stone events (KSEs).

Methods

This Phase 3, open-label, single-arm study enrolled pts with PH1 age <6 years, eGFR >45 mL/min/1.73m² (age ≥12M) or normal serum creatinine (age <12M), and urinary oxalate:creatinine ratio (UOx:Cr) > the upper limit of normal. Weight-based lumasiran was administered subcutaneously. Results are summarized descriptively.

Results

All pts (N=18) completed the 6M primary analysis, entered the 54M extension, and completed the study at M60. From baseline (BL) to M60, mean (SEM) change in spot UOx:Cr was −74% (4.2), and in plasma oxalate (POx), −25% (12.8). Annual rate of change (slope) in mean eGFR was +0.26 (SEM 0.8) mL/min/1.73m²/y. The most common lumasiran-related adverse events were mild, transient injection site reactions (n=3 pts [17%]). In 14 pts with NC at BL, NC grade (range 0/0-3/3) was improved at M60 in 12 (86%); none worsened. The 4 pts without NC at BL remained NC-free at M60. In the trial, 9 KSEs were reported in only 4 pts, whose spot UOx:Cr change ranged from −74.5% to −93.4% at M60. Two of the pts had 1 KSE each; 1 had BL grade 1/1 NC and improved to complete resolution (0/0) at M60, and 1 had no NC at BL or at M60. The other 2 pts had >1 KSE, and both had grade 3/3 NC at BL; at M60, 1 pt (5 KSEs) had complete NC resolution and the other (2 KSEs) had no change in NC grade.

Conclusion

Infants and young children with PH1 had sustained UOx and POx reductions over 60M of lumasiran treatment in ILLUMINATE-B, with stable eGFR and acceptable safety. NC grade improved in most pts, and most did not have KSEs. The 4 pts with KSEs had UOx reductions and changes in NC grade consistent with those of other trial pts.

Funding

• Commercial Support – Alnylam Pharmaceuticals

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025v7er7rv3