Kidney Week

Abstract: PO2358

Efficacy and Safety of Ravulizumab in Pediatric Patients with Atypical Hemolytic Uremic Syndrome Naïve to Complement Inhibitor Treatment: 26-Week and 1-Year Data

Session Information

• Pediatric Nephrology: Glomerular Disease and Transplantation
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1700 Pediatric Nephrology

Authors

• Ariceta, Gema, Hospital Vall d'Hebron, Barcelona, Catalunya, Spain

Gema Ariceta,

• Dixon, Bradley P., University of Colorado School of Medicine, Aurora, Colorado, United States

Bradley P. Dixon,

• Kim, Seong heon, Pusan National University Children's Hospital, Seoul, Korea (the Republic of)

Seong heon Kim,

• Kapur, Gaurav, Children's Hospital of Michigan, Detroit, Michigan, United States

Gaurav Kapur,

• Mauch, Teri Jo, University of Nebraska Medical Center, Omaha, Nebraska, United States

Teri Jo Mauch,

• Ortiz, Stephan, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Stephan Ortiz,

• Vallee, Marc, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Marc Vallee,

• Denker, Andrew E., Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States

Andrew E. Denker,

• Kang, Hee Gyung, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Hee Gyung Kang,

• Greenbaum, Larry A., Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, United States

Larry A. Greenbaum,

Background

Ravulizumab is a complement C5 inhibitor derived from eculizumab, with an increased half–life extending the maintenance dosing schedule from every 2–3 to every 4–8 weeks. We evaluated the efficacy and safety of ravulizumab to resolve active thrombotic microangiopathy (TMA) in children with atypical hemolytic uremic syndrome (aHUS) naïve to complement inhibitors.

Methods

ALXN1210-aHUS-312 (NCT03131219) is a phase 3, single–arm trial in children with TMA due to aHUS. Patients received ravulizumab every 4–8 weeks, depending on bodyweight. The primary endpoint was complete TMA response (platelet count and lactate dehydrogenase normalization and ≥25% improvement in serum creatinine from baseline at 2 visits ≥28 days apart) through 26 weeks. Key secondary endpoints included eGFR and dialysis requirement. Patients were then followed in an ongoing extension period. Here we report efficacy outcomes through 1 year and safety from all available follow–up (median 82.6 weeks).

Results

Eighteen patients (mean [SD] age 6.4 [4.5] years; 55.6% female) were enrolled; 14 (77.8%) achieved complete TMA response by 26 weeks, and 3 more patients (94.4%) by 50 weeks. Further improvements in TMA parameters occurred with longer-term treatment (Table). Mean (SD) increase in eGFR from baseline was 85.4 (54.3) mL/min/1.73m² at 26 weeks, and 94.1 (50.7) at 50 weeks. Of 6 patients on dialysis at baseline, 5 (83.3%) discontinued dialysis by week 26, and the last patient by week 50. Complete free C5 inhibition was sustained through the trial. No unexpected adverse events, deaths, or meningococcal infections occurred.

Conclusion

Ravulizumab administration every 4–8 weeks improved hematologic and renal outcomes in 94% of patients, with no unexpected safety concerns. Renal function improved with longer-term treatment.

Complete TMA response components over time

Data shown as n (%). LDH, lactate dehydrogenase; TMA, thrombotic microangiopathy.

Funding

• Commercial Support –