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

被引:28
|
作者
Wong, Raymond Siu Ming [1 ,2 ]
Navarro-Cabrera, Juan Ramon [3 ]
Comia, Narcisa Sonia [4 ]
Goh, Yeow Tee [5 ]
Idrobo, Henry [6 ]
Kongkabpan, Daolada [7 ]
Gomez-Almaguer, David [8 ]
Al-Adhami, Mohammed [9 ]
Ajayi, Temitayo [9 ]
Alvarenga, Paulo [9 ]
Savage, Jessica [9 ]
Deschatelets, Pascal [9 ]
Francois, Cedric [9 ]
Grossi, Federico [9 ]
Dumagay, Teresita [10 ]
机构
[1] Chinese Univ Hong Kong, Prince Wales Hosp, Sir YK Pao Ctr Canc, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
[3] Edgardo Rebagliati Hosp, Dept Hematol, Lima, Peru
[4] Mary Mediatrix Med Ctr, Res Ctr, Lipa, Philippines
[5] Singapore Gen Hosp, Dept Haematol, Singapore, Singapore
[6] Julian Coronel Med Ctr, Dept Haematol, Cali, Colombia
[7] Songklanagarind Hosp, Dept Med, Songkhla, Thailand
[8] Dr Jose Eleuterio Gonzalez Univ Hosp, Dept Haematol, Monterrey, Mexico
[9] Apellis Pharmaceut, Waltham, MA USA
[10] Makati Med Ctr, Dept Cellular Therapeut, Makati, Philippines
关键词
ECULIZUMAB; PNH; MECHANISM; FATIGUE; DISEASE;
D O I
10.1182/bloodadvances.2022009129
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 & GE;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 & GE;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.
引用
收藏
页码:2468 / 2478
页数:11
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