ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

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

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
  • Groothoff, Jaap, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands
  • Frishberg, Yaacov, Shaare Zedek Medical Center, Jerusalem, Israel
  • Hulton, Sally, Birmingham Women’s and Children's Hospital, Birmingham, United Kingdom
  • Koren, Michael, Jacksonville Center for Clinical Research, Jacksonville, Florida, United States
  • Overcash, Jeffrey Scott, eStudySite, San Diego, California, United States
  • SELLIER-LECLERC, Anne-Laure All, Hospices Civils de Lyon, Lyon, France
  • Deschênes, Georges, Hôpital Robert-Debré, Paris, France
  • Shasha-Lavsky, Hadas, Galilee Medical Center, Nahariya, North, Israel
  • Hayes, Wesley Nathan, Great Ormond Street Hospital, London, United Kingdom
  • Fuster, Daniel G., Bern University Hospital, University of Bern, Bern, Switzerland
  • Magen, Daniella, Rambam Health Care Campus, Haifa, Israel
  • Moochhala, Shabbir H., Royal Free Hospital, London, United Kingdom
  • Coenen, Martin, University Hospital Bonn, Bonn, Germany
  • Simkova, Eva, Al Jalila Children's Hospital, Dubai, United Arab Emirates
  • Garrelfs, Sander F., Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands
  • Sas, David J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Meliambro, Kristin, The Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Ngo, Taylor, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
  • Fujita, Kenji, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
  • Gansner, John M., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
  • McGregor, Tracy, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
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