Kidney Week

Abstract: SA-OR64

Ravulizumab in Atypical Hemolytic Uremic Syndrome: Final Analysis of Efficacy and Safety Outcomes in Two Phase 3 Trials

Session Information

• Glomerular Diseases: Clinical Advances
  October 26, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Dixon, Bradley P., Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States

Bradley P. Dixon, MD, FASN

• Kavanagh, David, National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Translational and Clinical Research Institute, Newcastle University, Newcastle, United Kingdom

David Kavanagh, MBChB, PhD

• Adams, Brigitte, University Hospital UZ Leuven, Leuven, Belgium

Brigitte Adams, MD

• Kang, Hee Gyung, Division of Pediatric Nephrology, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Hee Gyung Kang, MD, PhD

• Wang, Edward, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Edward Wang

• Garlo, Katherine, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Katherine Garlo, MD

• Ogawa, Masayo, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Masayo Ogawa, MD

• Cataland, Spero R., Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio, United States

Spero R. Cataland, MD

• Miyakawa, Yoshitaka, Department of Hematology, Saitama Medical University, Saitama, Japan

Yoshitaka Miyakawa, MD

• Luque, Yosu, Renal Intensive Care Unit, Nephrology Department, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France

Yosu Luque, MD, PhD

• Taylor, Veronica, Division of Pediatric Nephrology, University of Nebraska Medical Center, Children’s Nebraska, Omaha, Nebraska, United States

Veronica Taylor, MD

• Greenbaum, Larry A., Division of Pediatric Nephrology, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia, United States

Larry A. Greenbaum, MD, PhD

Background

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab (RAV) is a complement C5 inhibitor (C5i) approved for the treatment of aHUS.

Methods

This analysis reports final efficacy and safety data from two phase 3, single-arm clinical trials of C5i-naive adults (NCT02949128) and pediatric patients (pts) (NCT03131219) who were C5i-naive or switched to RAV from eculizumab (pediatric switch pts). Intravenous RAV was administered every 4–8 weeks, depending on body weight, in pts with aHUS. The primary endpoint was complete TMA response (platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, at two consecutive assessments ≥4 weeks apart). The primary endpoint evaluation was at Week 26; the extension period was up to 4.5 years or product approval/registration (whichever occurred first).

Results

54 pts completed the study (C5i-naive adults: n=28; C5i-naive pediatric pts: n=16; pediatric switch pts: n=10). The median (interquartile range) treatment duration was 130 (49–178) weeks for C5i-naive adults, 131 (15–160) weeks for C5i-naive pediatric pts, and 114 (114–123) weeks for pediatric switch pts. Among pts with available genetic data, 12/45 (27%) C5i-naive adults, 10/17 (59%) C5i-naive pediatric pts, and 6/10 (60%) pediatric switch pts had complement abnormalities and entered the extension. In C5i-naive adults (n=56), complete TMA response rates were 54% at Week 26 and 64% at end of study. In C5i-naive pediatric pts (n=20), complete TMA response rates were 75% at Week 26 and 90% at end of study. Among C5i-naive adults and pediatric pts, mean eGFR gradually improved up to Week 26 and remained stable until the end of the study. Most adverse events and serious adverse events were Grade 1 or 2 and occurred up to Week 26. No meningococcal infections were reported.

Conclusion

This final analysis over a median of 114–131 weeks demonstrated that continuation of RAV treatment is associated with sustained control of aHUS and clinical benefit through improvement and long-term preservation of renal function, with no unexpected safety concerns.

Funding

• Commercial Support – Alexion, AstraZeneca Rare Disease.