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Abstract: FR-PO906

C3 Inhibition with APL-2 Targets the Underlying Disease Process of C3G Complement Hyperactivity and Improves Proteinuria

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials


  • Dixon, Bradley P., Children's Hospital of Colorado, Aurora, Colorado, United States
  • Greenbaum, Larry A., Emory University, Atlanta, Georgia, United States
  • Huang, Liwei, Tidewater Kidney Specialists, Inc., Chesapake, Virginia, United States
  • Mccabe, James Carden, Southeastern Nephrology Associates, Wilmington, North Carolina, United States
  • Rajan, Sandeep K., University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Robertson, Nick, Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Kocinsky, Hetal S., Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Garovoy, Marvin R., Independent Consultant, Ex-Equals, LLC, Sausalito, California, United States
  • Di casoli, Carl, Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Deschatelets, Pascal, Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Francois, Cedric G., Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Grossi, Federico, Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States

C3G is a rare disease of complement dysregulation in which inappropriate C3 activation leads to excessive production of C3 breakdown products. The prognosis is poor with 30 – 50% of patients reaching end-stage renal disease within 10 years of diagnosis. APL-2, a cyclic peptide that inhibits C3 activation, has the potential to address the underlying pathophysiology of C3G. The study aims to assess whether APL-2 inhibits C3 activation, and improves proteinuria, in patients with C3G.


Adult and adolescent patients with primary C3G, proteinuria > 0.75 mg protein/mg creatinine and eGFR ≥ 30 ml/min/1.73 m2, were eligible for this Phase 2 open-label study to assess the safety and biological activity of APL-2 over 48 weeks. Eight C3G patients were recruited. Biological activity was assessed by changes from baseline in serum C3 and proteinuria. Proteinuria was quantitated by urine protein-to-creatinine ratio (uPCR) from a 24-hour urine, or as the mean from triplicate first-morning urine samples. Data are reported through Study Day 84 (12 weeks) for the first three patients. Data for all eight patients through Study Day 84 are planned for November, 2019.


Patient 1 was non-compliant with APL-2 dosing, and so data from this patient is not presented. In Patients 2 and 3, baseline serum C3 was low (≤ 13 mg/dL; normal range 90 – 180 mg/dL) and increased to > 130 mg/dL by Day 14 of APL-2 treatment. Both patients also had substantial improvements in proteinuria by Day 84, as evidenced by improvements in uPCR and serum albumin. In Patient 2, uPCR decreased from a baseline of 6.6 to 0.36 mg/mg on Day 84, with an increase in serum albumin from 2.4 to 4.4 g/dL. Patient 3 had a decrease in uPCR from a baseline of 3.2 to 1.6 mg/mg on Day 84, with a corresponding increase in serum albumin from 2.3 to 3.1 g/dL. APL-2 appears well-tolerated with no serious adverse events reported in C3G patients.


These data provide strong preliminary evidence that APL-2 targets the complement dysregulation of C3G with an increase in serum C3 levels and a reduction in proteinuria.


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