Kidney Week

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

• High-Impact Clinical Trials
  November 05, 2021 | Location: Live-Stream, Virtual Only
  Abstract Time: 11:15 AM - 11:30 AM

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

Mini Michael, MD

• Groothoff, Jaap, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands

Jaap Groothoff,

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

Hadas Shasha-Lavsky,

• Lieske, John C., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

John C. Lieske,

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

Yaacov Frishberg,

• Simkova, Eva, Al Jalila Children's Specialty Hospital, Dubai, Dubai, United Arab Emirates

Eva Simkova,

• Sellier-Leclerc, Anne-Laure All, Hopital Femme Mere Enfant, Bron, Auvergne-Rhône-Alpes , France

Anne-Laure All Sellier-Leclerc,

• Devresse, Arnaud, Cliniques universitaires Saint-Luc, Bruxelles, Belgium

Arnaud Devresse,

• Guebre Egziabher, Fitsum, Groupement Hospitalier Edouard Herriot Service de soins palliatifs, Lyon, Auvergne-Rhône-Alpes , France

Fitsum Guebre Egziabher,

• Bakkaloglu, Sevcan A., Gazi Universitesi, Ankara, Ankara, Turkey

Sevcan A. Bakkaloglu,

• Mourani, Chebl, Hotel-Dieu de France Hospital, Beirut, Lebanon

Chebl Mourani,

• Saqan, Rola, King Abdullah University Hospital, Ramtha, Irbid, Jordan

Rola Saqan,

• Singer, Richard F., Canberra Health Services, Garran, Australian Capital Territory, Australia

Richard F. Singer,

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

Richard G. Willey,

• Habtemarian, Bahru A., Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States

Bahru A. Habtemarian,

• Bhan, Ishir, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States

Ishir Bhan,

• McGregor, Tracy, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States

Tracy McGregor,

• Magen, Daniella, Rambam Health Care Campus, Haifa, Haifa, Israel

Daniella Magen,

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 – Alnylam Pharmaceuticals