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Abstract: PO1624

ILLUMINATE-B, a Phase 3 Open-Label Study to Evaluate Lumasiran, an RNAi Therapeutic, in Young Children with Primary Hyperoxaluria Type 1 (PH1)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Michael, Mini, Department of Pediatrics, Texas Children's Hospital, and Baylor College of Medicine, Houston, Texas, United States
  • Deschênes, Georges, Hospital Robert Debré, Paris, France
  • Cochat, Pierre, Centre for Rare Renal Diseases & Inserm Pediatric Clinical Investigation Centre – Hospices Civils de Lyon and Université de Lyon, Lyon, France
  • Magen, Daniella, Rambam Health Care Campus, Haifa, Israel
  • van't Hoff, William, Great Ormond Street Hospital for Children, Great Ormond Street Hospital For Children NHS Foundation Trust, London, London, United Kingdom
  • Sas, David J., Mayo Clinic, Rochester, Minnesota, United States
  • Schalk, Gesa, University of Bonn, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Bonn, Nordrhein-Westfalen, Germany
  • Shasha-Lavsky, Hadas, Galilee Medical Center, Nahariya, Israel, Nahariya, Israel
  • Hayes, Wesley Nathan, Great Ormond Street Hospital for Children, Great Ormond Street Hospital For Children NHS Foundation Trust, London, London, United Kingdom
  • Bae, Kyounghwa, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Seddighzadeh, Ali, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Garg, Pushkal, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Vaishnaw, Akshay, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • McGregor, Tracy, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Fujita, Kenji, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Frishberg, Yaacov, Shaare Zedek Medical Center, Jerusalem, Israel
Background


PH1 is a rare genetic disorder that often presents in young children. It is caused by hepatic oxalate overproduction leading to recurrent kidney stones, nephrocalcinosis, progressive kidney failure, and multiorgan damage from systemic oxalosis. There are no approved pharmacologic therapies for PH1. Lumasiran is a subcutaneously-administered investigational RNAi therapeutic that reduces hepatic oxalate production by targeting glycolate oxidase. In ILLUMINATE-A, a randomized, placebo-controlled Phase 3 study in patients with PH1 ≥6 years, lumasiran demonstrated an acceptable safety profile. The study met its primary efficacy endpoint [percent change from baseline, relative to placebo, in 24hr urinary oxalate (UOx) excretion averaged across months 3 to 6, P<0.001] and all tested secondary endpoints. Here, we present results from ILLUMINATE-B, an ongoing open-label Phase 3 study to evaluate efficacy and safety of lumasiran in young children with PH1.

Methods

Key inclusion criteria: <6 years, confirmed PH1 diagnosis, eGFR >45 mL/min/1.73m2 if ≥12 months or normal serum creatinine for age if <12 months. Patients received lumasiran 3×monthly, then monthly or quarterly. Primary endpoint: percent change in UOx excretion from baseline to month 6.

Results

Eighteen patients enrolled, including 4 patients <2 years; median age at first dose 4.3 years (range: 0.3-6). The baseline mean spot urinary oxalate:creatinine (UOx:Cr) was 0.63 mmol/mmol (range: 0.17-1.71), equivalent to 5.8×ULN for age. As of March 2020, there were no lumasiran-related serious adverse events; no deaths, severe adverse events, or treatment discontinuations. The most common adverse events related to lumasiran were mild, transient injection site reactions in 3/18 patients. Results from the complete primary analysis period (primary and secondary endpoints) will be presented.

Conclusion

Lumasiran demonstrated an acceptable safety profile in this interim analysis of ILLUMINATE-B. These results are consistent with those observed in ILLUMINATE-A in older children and adults and support the continued development of lumasiran for PH1.

Funding

  • Commercial Support