ASSESSMENT OF LONG-TERM RENAL FUNCTION IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH RAVULIZUMAB IN A PHASE 3 OPEN-LABEL STUDY.
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All Authors
Nagalla, S.
Kelly, R.
Yu, J.
Campolo, B.
Fattizzo, B.
Szer, J.
Jang, J.
LTHT Author
Kelly, Richard
LTHT Department
Oncology
Haematology
Haematology
Contributor Profession (Non Medical)
Publication Date
2025
Item Type
Conference Abstract
Language
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Abstract
Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, hematologic disorder characterized by uncontrolled terminal complement activation leading to intravascular hemolysis, thrombotic events, organ damage, and pre-mature mortality.1 A substantial proportion of patients with PNH experience renal dysfunction,1 with one study showing that 64% of patients with PNH had evidence of chronic kidney disease (CKD).2 It is estimated that CKD contributes to 8-18% of PNH-related deaths.2 Treatment of PNH with the complement C5 inhibitors eculizumab and ravulizumab, now as current standard of care, effectively inhibits terminal complement activity, resulting in control of intravascular hemolysis, a reduction in thrombotic events, and lower mortality and morbidity. Patients with PNH treated with eculizumab have shown improvement in renal function, with 93.1% showing an improved or stabilized CKD score after 36 months of treatment.2 Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab, designed to achieve immediate, complete, and sustained C5 inhibition at an extended dosing interval of every 8 weeks (Q8W) versus every 2 weeks (Q2W) for eculizumab. Aims To assess long-term renal function in patients with PNH receiving ravulizumab during the phase 3, open-label 302 study (NCT03056040). Methods In total, 195 adults (>= 18 years of age) with PNH on eculizumab (900 mg Q2W) for > 6 months were randomized 1:1 to ravulizumab (n = 97; weight-based dosing Q8W) or to continue eculizumab (n = 98) for 26 weeks; after this, all patients received ravulizumab in an open-label extension for up to 4 years. In this exploratory analysis, we evaluated estimated glomerular filtration rate (eGFR), a measure of renal function, for up to 3 years of ravulizumab treatment. As there were no predefined criteria for recording renal failure, previous history of renal failure in this patient population was investigator recorded. Results Of 195 patients randomized, 11/97 (11.3%) and 7/98 (7.1%) of patients in the ravulizumab and eculizumab treatment groups, respectively, had been previously diagnosed with renal failure at any time point prior to consent according to the investigator. At baseline, mean (standard deviation) eGFR levels were 103.2 (29.9) mL/min/1.73 m2 and 99.6 (30.9) mL/min/1.73 m2 in the ravulizumab and eculizumab treatment groups, respectively, indicating normal renal function (eGFR >= 90 mL/min/1.73 m2).3 Up to 26 weeks, eGFR levels remained stable in patients treated with ravulizumab or eculizumab (105.5 [31.0] and 99.3 [29.0] mL/min/1.73 m2, respectively, on day 183; Figure). Following continuation of or switch to ravulizumab, eGFR levels remained stable up to 3 years (95.1 [24.8] and 92.0 [28.5] mL/min/1.73 m2, respectively, on day 1093; Figure). Summary/Conclusion Up to 26 weeks, mean eGFR levels remained stable in patients randomized to ravulizumab or eculizumab and were indicative of normal renal function. Following the switch to open-label ravulizumab, patients with PNH maintained stable eGFR levels up to 3 years. Overall, these findings demonstrate the sustained benefit of long-term ravulizumab treatment in maintaining renal function in patients with PNH previously treated with eculizumab. Brodsky RA. Blood 2014;124:2804-11. Hillmen P. Br J Haematol 2013;62:62-73. National Kidney Foundation. Am J Kidney Dis 2002;39:S1-266.
Journal
HemaSphere