Kidney Week

Abstract: FR-PO229

Long-Term Efficacy and Safety of Lumasiran in Patients with Primary Hyperoxaluria Type 1: Final Analysis of the ILLUMINATE-A Trial

Session Information

• Mineral Bone Disease: Transplant and Kidney Stones
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Saland, Jeffrey, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Jeffrey Saland, MD, MS

• Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States

John C. Lieske, MD, FASN

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

Richard G. Willey, MS

• Frishberg, Yaacov, Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel

Yaacov Frishberg, MD

• Coenen, Martin, Institute of Clinical Chemistry and Clinical Pharmacology, Bonn, Germany

Martin Coenen, MD

• Hogan, Julien, Pediatric Nephrology Department, Hopital Robert-Debré, APHP, Paris, France

Julien Hogan, MD, PhD, MPH

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

Cristin Kaspar, MD, MS

• Hulton, Sally, Department of Nephrology, Birmingham Women’s and Children's Hospital, Bermingham, United Kingdom

Sally Hulton, MD, MBChB

Background

Primary hyperoxaluria type 1 (PH1) is characterized by hepatic oxalate overproduction, kidney stones, and progressive kidney disease. Lumasiran is approved to treat PH1 in pediatric and adult patients (pts). Here we report final, 60-month (M) data from ILLUMINATE-A (NCT03681184).

Methods

ILLUMINATE-A is a study in pts age ≥6 y with PH1 and eGFR ≥30 mL/min/1.73m². A 6M double-blind, placebo-controlled primary analysis period was followed by an extension period of up to 54M in which all pts received lumasiran.

Results

Of 39 pts enrolled, 25/26 (lumasiran/lumasiran group) and 13/13 (placebo/lumasiran group) completed the study. Mean 24-h urinary oxalate (UOx) reductions at end of study (EOS) relative to baseline (BL) were 54% (lumasiran/lumasiran; 60M post–lumasiran initiation) and 56% (placebo/lumasiran; 54M post–lumasiran initiation). For each time point in the extension period, ≥50% of pts in each group achieved 24-h UOx excretion ≤1.5 × upper limit of normal (0.514 mmol/24h/1.73m²): 50%–88% (lumasiran/lumasiran) and 54%–92% (placebo/lumasiran). Mean reductions in plasma oxalate from BL to EOS were 37% and 50% in the lumasiran/lumasiran and placebo/lumasiran groups, respectively. During the first 6M of lumasiran treatment, plasma glycolate increased (mean change from BL, 119% [lumasiran/lumasiran] and 154% [placebo/lumasiran]), then plateaued and remained stable. From BL through EOS, eGFR remained stable (mean [SEM] change from BL, −2.892 [2.747] and −12.860 [3.894] mL/min/1.73m² in the lumasiran/lumasiran and placebo/lumasiran groups, respectively). Kidney stone event (KSE) rates were low (0.47/person-year [PY] and 0.54/PY in the lumasiran/lumasiran and placebo/lumasiran groups, respectively, overall during lumasiran treatment; 0.09/PY and 0/PY, respectively, during the final 6M of the study). Medullary nephrocalcinosis (NC) grade improved at EOS in 16/20 pts with NC. The most common lumasiran-related adverse events were mild injection-site reactions (36% of pts).

Conclusion

Long-term lumasiran treatment (54–60M) in pts with PH1 led to sustained UOx reduction, with an acceptable safety profile and encouraging clinical outcomes data (low rates of eGFR decline, minimal KSEs, and improved medullary NC).

Funding

• Commercial Support – Alnylam Pharmaceuticals