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Abstract: FR-OR64

ILLUMINATE-C, a Single-Arm, Phase 3 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 and CKD Stages 3b-5, Including Those on Hemodialysis

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Michael, Mini, Texas Children's Hospital, Houston, Texas, United States
  • Groothoff, Jaap, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Shasha-Lavsky, Hadas, Galilee Medical Center, Nahariya, North, Israel
  • Lieske, John C., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Frishberg, Yaacov, Shaare Zedek Medical Center, Jerusalem, Jerusalem, Israel
  • Simkova, Eva, Al Jalila Children's Specialty Hospital, Dubai, Dubai, United Arab Emirates
  • Sellier-Leclerc, Anne-Laure All, Hopital Femme Mere Enfant, Bron, Auvergne-Rhône-Alpes , France
  • Devresse, Arnaud, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
  • Guebre Egziabher, Fitsum, Groupement Hospitalier Edouard Herriot Service de soins palliatifs, Lyon, Auvergne-Rhône-Alpes , France
  • Bakkaloglu, Sevcan A., Gazi Universitesi, Ankara, Ankara, Turkey
  • Mourani, Chebl, Hotel-Dieu de France Hospital, Beirut, Lebanon
  • Saqan, Rola, King Abdullah University Hospital, Ramtha, Irbid, Jordan
  • Singer, Richard F., Canberra Health Services, Garran, Australian Capital Territory, Australia
  • Willey, Richard G., Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Habtemarian, Bahru A., Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Bhan, Ishir, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • McGregor, Tracy, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Magen, Daniella, Rambam Health Care Campus, Haifa, Haifa, Israel
Background

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by hepatic overproduction of oxalate, leading to progressive kidney disease. As kidney function declines, oxalate elimination is compromised and plasma oxalate (POx) increases, leading to systemic oxalosis. In CKD stages 3b–5, elevated POx is directly related to the pathophysiology of oxalosis and reduction of POx is a relevant clinical trial endpoint. We present results from the 6-month primary analysis period of ILLUMINATE-C, a single-arm, phase 3 study to evaluate lumasiran, an RNAi therapeutic which inhibits oxalate production, in patients with PH1 and impaired kidney function.

Methods

Key inclusion criteria: genetically confirmed PH1 diagnosis, eGFR≤45 mL/min/1.73m2, POx≥20 μmol/L (upper limit of normal=12 μmol/L). Cohort A: patients who did not require dialysis or kidney transplantation at study start. Cohort B: patients on hemodialysis. Primary endpoints: percent change in POx from baseline to Month (M) 6 (cohort A); percent change in pre-dialysis POx from baseline to M6 (cohort B).

Results

Twenty-one patients enrolled, 6 in cohort A and 15 in cohort B. The baseline mean (SD) POx was 64.7 (41.3) µmol/L in cohort A and 108.4 (29.5) µmol/L in cohort B. In cohorts A and B, respectively, lumasiran led to 33.33% (95%CI:−15.16, 81.82) and 42.43% (95%CI:34.15, 50.71) least-square mean reductions in POx from baseline to M6 (averaged across M3-6). Lumasiran also demonstrated a reduction in urinary oxalate (cohort A). The most common adverse events (AEs) related to lumasiran were injection-site reactions, all of which were mild. There were no serious or severe AEs related to lumasiran nor deaths of patients that received lumasiran. There were no treatment discontinuations or study withdrawals.

Conclusion

Lumasiran resulted in substantial reductions in POx in PH1 patients with CKD 3b-5, with an acceptable safety profile through M6. Changes of this magnitude in POx may impact long-term clinical outcomes, including those related to systemic oxalosis, which will be evaluated in the extension period of the study.

Funding

  • Commercial Support –