Kidney Week

Abstract: FR-PO592

Lumasiran for Primary Hyperoxaluria Type 1 and Impaired Kidney Function: 24-Month Analysis of the Phase 3 ILLUMINATE-C Trial

Session Information

• Genetic Diseases: Tubulopathies
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

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

John C. Lieske,

• Magen, Daniella, Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel

Daniella Magen,

• Sellier-Leclerc, Anne-Laure All, Hôpital Femme Mère Enfant en Centre d’Investigation Clinique INSERM, Hospices Civils de Lyon, ERKnet, Bron, France

Anne-Laure All Sellier-Leclerc,

• Shasha-Lavsky, Hadas, Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel

Hadas Shasha-Lavsky,

• Simkova, Eva, Nephrology - Medical Affairs, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates

Eva Simkova,

• Devresse, Arnaud, Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Arnaud Devresse,

• Michael, Mini, Texas Children’s Hospital/Baylor College of Medicine, Houston, Texas, United States

Mini Michael,

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

Yaacov Frishberg,

• Bakkaloglu, Sevcan A., Department of Pediatric Nephrology, Faculty of Medicine, Gazi University, Ankara, Turkey

Sevcan A. Bakkaloglu,

• Mourani, Chebl, Pediatrics, Hôtel-Dieu de France Hospital (HDF), Beirut, Lebanon

Chebl Mourani,

• Saqan, Rola, Pharmaceutical Research Center - Jordan University of Science and Technology, Irbid, Jordan

Rola Saqan,

• Singer, Richard F., Senior Staff Specialist, Renal Service, Canberra Health Services, Garran, Australian Capital Territory, Australia

Richard F. Singer,

• Guzzo, Isabella, Ospedale Pediatrico Bambino Gesu, Rome, Italy

Isabella Guzzo,

• Makarova, Nune, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Nune Makarova,

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

Richard G. Willey,

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

Cristin Kaspar,

• Gansner, John M., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

John M. Gansner,

• Groothoff, Jaap, Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands

Jaap Groothoff,

Background

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder in which hepatic oxalate overproduction can lead to chronic kidney disease (CKD). Plasma oxalate (POx) increases with declining kidney function, leading to systemic oxalosis. Lumasiran, an RNA interference therapeutic that reduces hepatic oxalate production, administered to patients with PH1 and CKD 3b–5 in the ILLUMINATE-C trial (NCT04152200), resulted in decreased POx at month (M) 6 and 12 with acceptable safety. Here we present M24 results.

Methods

ILLUMINATE-C is an ongoing, single-arm study evaluating lumasiran in patients of all ages with PH1, eGFR ≤45 mL/min/1.73m² including hemodialysis (HD), and POx ≥20 μmol/L. The 6M primary analysis period is followed by a 54M extension period.

Results

Of 21 patients who entered the study, 5 of 6 (83%) assigned at study start to Cohort A (no HD) and 12 of 15 (80%) assigned to Cohort B (on HD) completed the M24 visit. Mean reduction from baseline in POx at M24 was 60.5% (Cohort A) and 30.6% (Cohort B). Two Cohort A patients with low baseline eGFR (8.6, 16 mL/min/1.73m²) initiated HD. Two Cohort B patients who underwent kidney-only transplantation remained in the study with a functional graft after 16 and 21 months and comparable POx levels to 2 patients who underwent combined liver-kidney transplant. In patients with an ejection fraction (EF) <55% at baseline, 2 of 3 had improvement of ≥5% at M24; none met criteria for EF worsening. Mild injection site reactions were the most common lumasiran-related AEs, occurring in 5 of 21 (24%) patients overall. No deaths or lumasiran-related serious/severe AEs, discontinuations, or withdrawals occurred.

Conclusion

POx reductions with lumasiran were maintained at M24 with an acceptable safety profile in PH1 patients with CKD 3b–5, including those on HD, and in patients with an isolated kidney transplant. Noninvasive indicators of systemic oxalosis including EF appear stable or possibly improving after 2 years of treatment in this study population.

Funding

• Commercial Support – Alnylam Pharmaceuticals