Kidney Week

Abstract: PO2637

12-Month Analysis of ILLUMINATE-A, a Phase 3 Study of Lumasiran: Sustained Oxalate Lowering and Kidney Stone Event Rates in Primary Hyperoxaluria Type 1

Session Information

• Late-Breaking Clinical Trials Posters
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

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

Jeffrey Saland,

• Groothoff, Jaap, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Jaap Groothoff,

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

Yaacov Frishberg,

• Hulton, Sally, Birmingham Women’s and Children's Hospital, Birmingham, United Kingdom

Sally Hulton,

• Koren, Michael, Jacksonville Center for Clinical Research, Jacksonville, Florida, United States

Michael Koren,

• Overcash, Jeffrey Scott, eStudySite, San Diego, California, United States

Jeffrey Scott Overcash,

• SELLIER-LECLERC, Anne-Laure All, Hospices Civils de Lyon, Lyon, France

Anne-Laure All SELLIER-LECLERC,

• Deschênes, Georges, Hôpital Robert-Debré, Paris, France

Georges Deschênes,

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

Hadas Shasha-Lavsky,

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

Wesley Nathan Hayes,

• Fuster, Daniel G., Bern University Hospital, University of Bern, Bern, Switzerland

Daniel G. Fuster,

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

Daniella Magen,

• Moochhala, Shabbir H., Royal Free Hospital, London, United Kingdom

Shabbir H. Moochhala,

• Coenen, Martin, University Hospital Bonn, Bonn, Germany

Martin Coenen,

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

Eva Simkova,

• Garrelfs, Sander F., Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Sander F. Garrelfs,

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

David J. Sas,

• Meliambro, Kristin, The Icahn School of Medicine at Mount Sinai, New York, New York, United States

Kristin Meliambro,

• Ngo, Taylor, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Taylor Ngo,

• Fujita, Kenji, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Kenji Fujita,

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

John M. Gansner,

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

Tracy McGregor,

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

John C. Lieske,

Background

ILLUMINATE-A is a Phase 3 trial of lumasiran, an investigational RNAi therapeutic that reduces hepatic oxalate production.

Methods

The trial enrolled 39 patients ≥6 years with primary hyperoxaluria type 1 (PH1) and eGFR≥30 mL/min/1.73m². The trial had a 6-month (M) double-blind, placebo-controlled period (DBP) and an extension period (EP).

Results

During the DBP, the least square mean treatment difference in 24hr urinary oxalate (UOx) excretion for lumasiran compared to placebo was –53.5% (p=1.7×10⁻¹⁴), and 84% of lumasiran-treated patients achieved near-normalization or normalization of 24hr UOx excretion at M6 (vs 0% placebo-treated patients). In the EP, the 13 patients initially randomized to placebo crossed over to lumasiran (P/L), demonstrating a similar time course and magnitude of UOx reduction. After 6M of treatment, their 24hr UOx mean percent reduction was 57.3% and a comparable proportion (77%) achieved near-normalization or normalization of 24hr UOx excretion. In patients initially randomized to lumasiran (L/L), the reduction in 24hr UOx was sustained through M12. The calculated rate (per 100 person-days) of renal stone events (RSE) in the L/L group decreased from a reported rate of 0.87 (95% CI: 0.70, 1.08) over the 12M prior to consent, to observed rates of 0.30 (95% CI: 0.17, 0.51) for the 6M DBP, to 0.23 (95% CI: 0.13, 0.43) with an additional 6M of lumasiran. In the P/L group, RSE rates remained stable from a reported rate of 0.15 (95% CI: 0.07, 0.31) over the 12M prior to consent, to 0.18 (95% CI: 0.07, 0.48) during the 6M DBP, followed by a decrease to 0.05 (95% CI: 0.01, 0.32) during the first 6M of lumasiran treatment. Consistent with the DBP, the most common adverse events related to lumasiran in the EP were mild, transient injection site reactions.

Conclusion

The UOx reduction observed in the DBP was replicated by placebo crossover patients, confirming the robustness of the result. Lower RSE rates after 6-12M of treatment with lumasiran are encouraging.

Funding

• Commercial Support –