Kidney Week

Abstract: SA-PO414

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

Session Information

• Genetic Diseases of the Kidney - III
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

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

Tracy McGregor,

• Hulton, Sally, Birmingham Childrens'' Hospital, Birmingham, United Kingdom

Sally Hulton,

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

Yaacov Frishberg,

• Cochat, Pierre, Université ClaudeBernard Lyon1-, Bron, France

Pierre Cochat,

• Groothoff, Jaap, Amsterdam UMC (Academic Medical Center), Amsterdam, Netherlands

Jaap Groothoff,

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

Daniella Magen,

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

Jerome Harambat,

• Hoppe, Bernd, University Hospital Bonn, Bonn, Germany

Bernd Hoppe,

• van't Hoff, William, Great Ormond Street Hospital, Lond, United Kingdom

William van't Hoff,

• Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States

Dawn S. Milliner,

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

John C. Lieske,

• Haslett, Patrick, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Patrick Haslett,

• Talamudupula, Sandeep, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

Sandeep Talamudupula,

• Erbe, David V., Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States

David V. Erbe,

• Deschênes, Georges, Hospital Robert Debre/Pediatric Nephrology, Paris, France

Georges Deschênes,

Background

PH1 is a rare genetic disorder characterized by persistent hepatic overproduction of oxalate. Oxalate crystalizes with calcium leading to recurrent kidney stones, nephrocalcinosis, progressive renal failure, and multiorgan damage from systemic oxalosis. Lumasiran is a subcutaneously-administered investigational RNAi therapeutic specifically designed to decrease oxalate production. In Phase 1/2, lumasiran demonstrated an acceptable safety profile and clinically significant urinary oxalate (UOx) lowering in patients with PH1. Emerging data from the ongoing Phase 2 open-label extension (OLE) study will be presented.

Methods

Phase 2 OLE includes patients who completed the Phase 1/2 randomized, placebo-controlled, multicenter trial, evaluating lumasiran in patients with PH1 ≥6 years old, UOx ≥0.7mmol/1.73m²/day and eGFR >45mL/min/1.73m². Patients received 1 of 3 dosing regimens: 1mg/kg or 3mg/kg monthly x3 doses or 3mg/kg every 3 months x2 doses. After completing Phase 1/2, all patients enrolled in OLE, starting at their original dose unless a different dose was approved prior to dosing in OLE. Endpoints include safety and change in 24-hour UOx.

Results

The Phase 1/2 study enrolled 20 patients with PH1 at 9 sites in 5 countries; mean age 14.9 years (range: 6-43), mean baseline UOx 1.69mmol/1.73m²/day (range: 0.83–2.97). As of February 2019, 18 patients were dosed in OLE for median of 4 months (range: 0.03–8.36 ). Continued dosing with lumasiran was well tolerated, with no discontinuations or drug-related serious adverse events. Adverse events were reported in 12/18 (66.7%) patients; majority were mild in severity and assessed as unrelated to study drug. Mean max reduction in UOx relative to Phase 1/2 baseline was 72% (N=9) and mean reduction at day 85 was 69% (N=7); all of these patients achieved normal or near normal levels of UOx.

Conclusion

To date, lumasiran has demonstrated an acceptable safety profile and clinically significant reduction in UOx in patients with PH1. A Phase 3 program evaluating efficacy and safety of lumasiran in patients with PH1 is ongoing.

Funding

• Commercial Support –