Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria.

Autor:	Wong RSM; Sir YK Pao Centre for Cancer & Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong, Hong Kong., Navarro-Cabrera JR; Department of Hematology, Edgardo Rebagliati Hospital, Lima, Peru., Comia NS; Research Center, Mary Mediatrix Medical Center, Lipa, Philippines., Goh YT; Department of Haematology, Singapore General Hospital, Singapore., Idrobo H; Department of Haematology, Julian Coronel Medical Center, Cali, Colombia., Kongkabpan D; Department of Medicine, Songklanagarind Hospital, Songkhla, Thailand., Gómez-Almaguer D; Department of Haematology, Dr. José Eleuterio González University Hospital, Monterrey, Mexico., Al-Adhami M; Apellis Pharmaceuticals, Waltham, MA., Ajayi T; Apellis Pharmaceuticals, Waltham, MA., Alvarenga P; Apellis Pharmaceuticals, Waltham, MA., Savage J; Apellis Pharmaceuticals, Waltham, MA., Deschatelets P; Apellis Pharmaceuticals, Waltham, MA., Francois C; Apellis Pharmaceuticals, Waltham, MA., Grossi F; Apellis Pharmaceuticals, Waltham, MA., Dumagay T; Department of Cellular Therapeutics, Makati Medical Centre, Makati City, Philippines.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Jun 13; Vol. 7 (11), pp. 2468-2478.
DOI:	10.1182/bloodadvances.2022009129
Abstrakt:	Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of pegcetacoplan vs control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n = 35) or control (n = 18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, -1870.5 U/L; control, -400.1 U/L; difference, -1470.4 U/L; 95% CI, -2113.4 to -827.3; P < .0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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