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Abstract: FR-OR67

Exploratory Results From the Phase 2 Study of Cemdisiran in Patients With IgA Nephropathy

Session Information

  • High-Impact Clinical Trials
    November 04, 2022 | Location: W415 Valencia, Orange County Convention Center‚ West Building
    Abstract Time: 12:00 PM - 12:15 PM

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials


  • Barratt, Jonathan, Leicester General Hospital, Leicester, Leicester, United Kingdom
  • Yeo, See Cheng, Tan Tock Seng Hospital, Singapore, Singapore
  • Fernstrom, Anders, Linkopings universitet, Linkoping, Östergötland, Sweden
  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
  • Sperati, John, Johns Hopkins University, Baltimore, Maryland, United States
  • Villanueva, Anthony Russell, National Kidney and Transplant Institute, Quezon City, National Capital Region, Philippines
  • Wu, Ming-Ju, Taichung Veterans General Hospital, Taichung, Taiwan
  • Wang, Dazhe, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Borodovsky, Anna, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Badri, Prajakta, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Yureneva, Elena, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Bhan, Ishir, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Cattran, Daniel C., Toronto General Hospital, Toronto, Ontario, Canada

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Proteinuria >1 g/day is a risk factor for progression to kidney failure; treatment options are limited. In IgA nephropathy, data suggest that activation of the lectin and alternative complement pathways lead to complement component 5 (C5) cleavage, and to production of C5a and the membrane attack complex (MAC), with subsequent inflammation and tissue injury. Cemdisiran is an investigational RNA interference therapeutic that suppresses liver production of C5.


This Phase 2 study is a randomized, double-blind, placebo-controlled trial (NCT03841448) of cemdisiran in adults with IgAN and proteinuria >1 g/day. Patients were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo once every 4 weeks (Q4W) alongside standard of care. Primary endpoint is change from baseline to Week 32 in 24-hour urine protein/creatinine ratio (UPCR). Exploratory endpoints include change from baseline to Week 32 in eGFR and change from baseline in complement activity and C5 levels over the study.


31 patients (22 cemdisiran, 9 placebo) were randomized: mean (SD) age, 39.7 (10.1) yrs. Mean (SD) baseline 24-hour UPCR g/g: cemdisiran 1.6 (1.0), placebo 2.0 (0.8). Cemdisiran led to a 37.4% (90% CI: -0.5, 61.0) adjusted geometric mean reduction in 24-hour UPCR compared with placebo at Week 32 (primary endpoint). eGFR data suggested stability at Week 32 following cemdisiran, in contrast to a decline shown in placebo-treated patients (median change from baseline [IQR] ml/min/1.73m2: cemdisiran 0 [-6.5, 3.5], placebo -6 [-9.5, -2.5]). Cemdisiran also led to a 98.7% (SD: 1.2) mean reduction from baseline in serum C5 at Week 32. Cemdisiran was generally well tolerated with no treatment-related serious or severe adverse events (AEs). AEs in ≥10% of cemdisiran-treated patients: injection site reactions (41%) and peripheral edema (14%).


Suppression of hepatic C5 production with cemdisiran led to clinically meaningful improvements in proteinuria in patients with IgAN; with cemdisiran generally well tolerated. These results support further investigation in this population.


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