Abstract: SA-PO062
Iptacopan in C5 Blockade for Refractory Atypical Hemolytic Uremic Syndrome
Session Information
- AKI: Clinical, Outcomes, and Trials - Management
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Tran, Minh-Ha, University of California Irvine - Department of Pathology - Division of Transfusion Medicine, Irvine, California, United States
- Ciurea, Stefan Octavian, University of California Irvine - Department of Medicine - Division of Hematology/Oncology-Bone Marrow Transplant Unit, Irvine, California, United States
- Desai, Sheetal, University of California Irvine - Department of Medicine - Division of Rheumatology, Irvine, California, United States
- Rezazadeh Kalebasty, Arash, University of California - Irvine - Department of Medicine - Division of Hematology/Oncology, Irvine, California, United States
- Nguyen, Matthew Duy Thanh Luyen, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Nguyen, Vu Quy, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Patel, Samir Dinesh, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Selamet, Umut, Harvard - Dana Farber Cancer Institute - Department of Medicine-Division of Oncology, Boston, Massachusetts, United States
- Hanna, Ramy Magdy, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
Introduction
Atypical Hemolytic Uremic Syndrome (aHUS) is a life-threatening disease related to mutations in the complement system resulting in overactivation and dysregulation of the alternate pathway. Currently, there are only two United States Food and Drug Administration (FDA) approved treatments for aHUS, eculizumab and ravulizumab, which target complement factor 5 (C5) and prevent the formation of C5b-9. Iptacopan (Fabhalta) is a small-molecule inhibitor of complement factor B (FB) that binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb). This limits the cleavage of C3 to the active fragment C3b and can prevent C3b-mediated extravascular hemolysis. We report the first known case of the factor B inhibition with Iptacopan in treatment of aHUS.
Case Description
21-year-old Pakastani male with heterozygous complement factor related protein 4 mutation and aHUS, had an initial partial response to eculizumab and then complete response to ravulizumab, which resulted in the patient coming off dialysis. Patient had a sudden and unexpected flare 2 years after his initial presentation. The treatment failure was not abated by redosing with ravulizumab, leading to the use of multiple advanced diagnostics (including artificial intelligence algorithms) to look for a possible differential. No malignancy or other aggravating factor was found even after bone marrow biopsy. Recent data on Iptacopan’s use in C5 refractory Paroxysmal Nocturnal Hemoglobinuria provided a therapeutic rationale. An application for the compassionate use of Iptacopan was filed and approved by the FDA. Patient’s blood counts completely recovered, his microangiopathic hemolytic anemia ceased, his acute kidney injury completely resolved thus permitting discontinuation of renal replacement therapy was discontinued. Human Anti-murine anti-drug antibodies were suspected as the cause of C5-blockade failure but could not be confirmed.
Discussion
To our knowledge this is the first report of using Iptacopan in treatment of aHUS in the United States. Larger clinical trials involving diverse patient populations are needed to validate these initial findings, assess safety, and establish Iptacopan as a potential treatment for the management of aHUS.