Kidney Week

Abstract: PO1647

Results from the Ongoing Phase 2 Open-Label Extension Study of Lumasiran, an Investigational RNAi Therapeutic, in Patients with Primary Hyperoxaluria Type 1 (PH1)

Session Information

• Genetic Diseases of the Kidneys: Non-Cystic - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

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

Yaacov Frishberg,

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

Sally Hulton,

• Cochat, Pierre, Centre for Rare Renal Diseases & Inserm Pediatric Clinical Investigation Centre – Hospices Civils de Lyon and Université de Lyon, Lyon, France

Pierre Cochat,

• Groothoff, Jaap, University of Amsterdam, Amsterdam, Netherlands

Jaap Groothoff,

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

Daniella Magen,

• Harambat, Jerome, Bordeaux University Hospital, Bordeaux, France

Jerome Harambat,

• Schalk, Gesa, University of Bonn, Bonn, Nordrhein-Westfalen, Germany

Gesa Schalk,

• van't Hoff, William, Great Ormond Street Hospital For Children, London, London, United Kingdom

William van't Hoff,

• Lesueur, Dayna, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Dayna Lesueur,

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

Tracy McGregor,

• Deschênes, Georges, Hospital Robert Debré, Paris, France

Georges Deschênes,

Background

PH1 is a rare genetic disorder characterized by hepatic overproduction of oxalate, leading to recurrent kidney stones, nephrocalcinosis, progressive renal failure, and multiorgan damage from systemic oxalosis. There are no approved pharmacologic therapies for PH1. Lumasiran is a subcutaneously-administered investigational RNAi therapeutic that decreases hepatic oxalate production by targeting glycolate oxidase. We present long-term safety and efficacy data of up to 22 months exposure from the ongoing Phase 2 open-label extension (OLE) study of lumasiran.

Methods

Phase 2 OLE includes patients with PH1, ≥6 years old, urinary oxalate (UOx) ≥0.7mmol/1.73m²/day, and eGFR >45mL/min/1.73m² who completed the Phase 1/2 study. Patients initially received lumasiran 1mg/kg monthly, 3mg/kg monthly or 3mg/kg quarterly, and all transitioned to 3mg/kg quarterly. Endpoints include safety and change in 24h UOx excretion.

Results

This trial enrolled all 20 patients from the Phase 1/2 study. At baseline of the parent study, patients had a mean age 14.9 years (range: 6-43), mean baseline UOx 2.24 mmol/1.73m²/day (range: 0.94, 5.18). As of January 2020, patients were dosed in OLE for a median of 15 months (range: 11–22). Adverse events were reported in 19/20 (95%) patients; all were mild or moderate and the majority were assessed as unrelated to study drug. There were no discontinuations or drug-related serious adverse events. The mean max reduction in 24h UOx relative to Phase 1/2 baseline was 74.5% (N=17) and 17/18 patients achieved normal or near normal levels of UOx. Plasma oxalate levels also decreased (mean max reduction 55.2%, N=19). Plasma and urinary glycolate increased and later stabilized, consistent with the effect of lumasiran on glycolate oxidase.

Conclusion

Lumasiran had an acceptable safety profile. Continued therapy with lumasiran maintained reduction of UOx to levels near or below the upper limit of normal, consistent with the Phase 1/2 study. These data further enable ongoing Phase 3 studies to evaluate lumasiran in patients with PH1 of all ages and at all stages of renal impairment.

Funding

• Commercial Support –