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Kidney Week

Abstract: PO2331

Efficacy and Safety of Ravulizumab in Pediatric Patients with Atypical Hemolytic Uremic Syndrome Previously Treated with Eculizumab: 26-Week and 1-Year Data

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Greenbaum, Larry A., Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, United States
  • Fujita, Naoya, Aichi Shoni Hoken Iryo Sogo Center, Obu, Aichi, Japan
  • Adams, Brigitte Valentine, Queen Fabiola Children's University Hospital, Brussels, Belgium
  • Madrid Aris, Alvaro, Children's Nephrology and Renal Transplantation Service, Children's Maternity Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
  • Ogawa, Masayo, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
  • Ortiz, Stephan, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
  • Vallee, Marc, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
  • Tanaka, Kazuki, Aichi Shoni Hoken Iryo Sogo Center, Obu, Aichi, Japan
Background

The complement C5 inhibitor eculizumab improves outcomes of atypical hemolytic uremic syndrome (aHUS) but must be administered every 2–3 weeks. Ravulizumab, engineered from eculizumab for a longer half–life, is efficacious and safe in adults with 8–week dosing intervals. This analysis was in eculizumab-treated children with aHUS.

Methods

ALXN1210-aHUS-312 (NCT03131219) is a phase 3, single–arm trial in complement inhibitor-naïve children (Cohort 1; reported separately) and children who were receiving treatment with eculizumab without thrombotic microangiopathy (TMA; Cohort 2; reported here). This analysis assessed TMA activity, and the pharmacodynamic measure serum free C5 levels after patients switched from eculizumab to ravulizumab treatment. Patients received loading doses then maintenance treatment with ravulizumab every 4 or 8 weeks, dependent on weight, for 26 weeks. An extension phase is ongoing; here we report data on efficacy through 1 year and safety from all available follow up (median 50.2 weeks).

Results

Ten patients (mean [SD] age 11 [5.0] years) were enrolled into Cohort 2; all completed the 26–week initial evaluation period and entered the extension. Mean eGFR, hematologic outcomes (platelet, lactate dehydrogenase and hemoglobin normalization), and fatigue measures remained stable during both trial periods. At 1-year, the mean (SD) changes from baseline were: eGFR, -3.9 (8.3) mL/min/1.75m2; platelets, −17.8 (54.6) ×109/L; LDH −10.7 (19.2) U/L; hemoglobin +4.5 (7.1) g/L. All patients were in the same eGFR category at 1 year as recorded at baseline (eGFR mL/min/1.73m2 ≥90, n=8; 60–89, n=1; 49–59, n=1). No patients required dialysis. Despite the increased dosing interval, serum free C5 levels were maintained below the threshold of 0.5 mg/mL. All patients experienced adverse events (AEs) but none discontinued the trial. No meningococcal infections occurred. One patient experienced serious AEs due to a respiratory tract infection.

Conclusion

Continued efficacy, no additional safety concerns and the benefit of reduced dosing frequency was demonstrated in pediatric patients with aHUS who were stable on eculizumab and switched to ravulizumab.

Funding

  • Commercial Support