Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegc...

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Veröffentlicht in:	Annals of hematology Jg. 101; H. 9; S. 1971 - 1986
Hauptverfasser:	Wong, Raymond S. M., Pullon, Humphrey W. H., Amine, Ismail, Bogdanovic, Andrija, Deschatelets, Pascal, Francois, Cedric G., Ignatova, Kalina, Issaragrisil, Surapol, Niparuck, Pimjai, Numbenjapon, Tontanai, Roman, Eloy, Sathar, Jameela, Xu, Raymond, Al-Adhami, Mohammed, Tan, Lisa, Tse, Eric, Grossi, Federico V.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022 Springer Nature B.V
Schlagworte:	Adult Anemia Biomarkers Blood diseases Bone marrow Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Complement Inactivating Agents - adverse effects Dehydrogenases Drug dosages FDA approval Hematology Hemoglobin Hemoglobins Hemoglobinuria, Paroxysmal - drug therapy Hemolysis Hospitals Humans Medicine Medicine & Public Health Monoclonal antibodies Oncology Original Original Article Peptides, Cyclic - adverse effects Pharmaceuticals Quality of life Hemoglobin LDH Phase I/II trials Safety Paroxysmal nocturnal hemoglobinuria (PNH) Quality of life
ISSN:	0939-5555, 1432-0584, 1432-0584
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Abstract	Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [ n = 3]; cohort 2: 270–360 mg up to day 365 [ n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 ( n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90–18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200).
AbstractList	Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [ n = 3]; cohort 2: 270–360 mg up to day 365 [ n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 ( n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90–18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200). Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [n = 3]; cohort 2: 270-360 mg up to day 365 [n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 (n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90-18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200).Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [n = 3]; cohort 2: 270-360 mg up to day 365 [n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 (n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90-18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200). Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [n = 3]; cohort 2: 270-360 mg up to day 365 [n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 (n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90-18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200). Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [n = 3]; cohort 2: 270–360 mg up to day 365 [n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 (n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90–18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200).
Author	Xu, Raymond Grossi, Federico V. Wong, Raymond S. M. Francois, Cedric G. Pullon, Humphrey W. H. Tse, Eric Numbenjapon, Tontanai Niparuck, Pimjai Tan, Lisa Amine, Ismail Deschatelets, Pascal Ignatova, Kalina Roman, Eloy Bogdanovic, Andrija Sathar, Jameela Issaragrisil, Surapol Al-Adhami, Mohammed
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Cites_doi	10.1182/blood-2008-01-133918 10.1038/nrdp.2017.28 10.1182/blood-2018-09-876805 10.1002/cncr.10245 10.1007/bf03019668 10.1182/asheducation-2016.1.208 10.1056/NEJMoa061648 10.1177/2040620720966137 10.1016/j.molimm.2017.06.039 10.1038/nrd4657 10.1182/blood-2005-04-1717 10.1182/blood.V130.Suppl_1.3471.3471 10.1056/NEJMoa2029073 10.1007/s00277-020-04052-z 10.1111/bjh.12347 10.1182/blood.2020004959 10.1016/0092-8674(93)90250-t 10.1016/s1040-8428(99)00052-9 10.1001/jama.293.13.1653 10.1111/ejh.12021 10.1073/pnas.90.11.5272 10.1016/j.cca.2019.03.1617 10.3389/fimmu.2019.01157 10.1371/journal.pone.0032327 10.4049/jimmunol.1203200 10.3389/fimmu.2018.01749 10.1182/blood-2007-06-095646 10.3324/haematol.2013.093161 10.1182/blood-2018-09-876136 10.1046/j.1365-2141.1997.d01-1984.x 10.1056/nejm199010253231707 10.1248/bpb.b15-00703 10.1002/j.1460-2075.1994.tb06240.x 10.1586/17474086.2014.953926 10.1134/s1990750821030069 10.1038/s41409-021-01372-0 10.3324/haematol.2019.236877 10.1038/ni.1923 10.1002/ajh.24278 10.1182/blood-2008-11-189944 10.1016/S0021-9258(18)42266-1 10.1155/2015/635670 10.2147/btt.s1420 10.1016/s0885-3924(02)00529-8 10.1002/ajh.25960
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Keywords	Hemoglobin LDH Phase I/II trials Safety Paroxysmal nocturnal hemoglobinuria (PNH) Quality of life
Language	English
License	2022. The Author(s). Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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PublicationCentury	2000
PublicationDate	2022-09-01
PublicationDateYYYYMMDD	2022-09-01
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PublicationDecade	2020
PublicationPlace	Berlin/Heidelberg
PublicationPlace_xml	– name: Berlin/Heidelberg – name: Germany – name: Berlin
PublicationTitle	Annals of hematology
PublicationTitleAbbrev	Ann Hematol
PublicationTitleAlternate	Ann Hematol
PublicationYear	2022
Publisher	Springer Berlin Heidelberg Springer Nature B.V
Publisher_xml	– name: Springer Berlin Heidelberg – name: Springer Nature B.V
References	Lee, Sicre de Fontbrune, Wong Lee Lee, Pessoa, Gualandro, Füreder, Ptushkin, Rottinghaus, Volles, Shafner, Aguzzi, Pradhan, Schrezenmeier, Hill (CR30) 2019; 133 Nakayama, Usuki, Echizen, Ogawa, Orii (CR26) 2016; 39 Risitano, Rotoli (CR17) 2008; 2 Ullman, Horn, Abraham, VanSlyck (CR5) 1963; 11 Schrezenmeier, Muus, Socié, Szer, Urbano-Ispizua, Maciejewski, Brodsky, Bessler, Kanakura, Rosse, Khursigara, Bedrosian, Hillmen (CR19) 2014; 99 Cella, Eton, Lai, Peterman, Merkel (CR35) 2002; 24 Parker, Omine, Richards, Nishimura, Bessler, Ware, Hillmen, Luzzatto, Young, Kinoshita, Rosse, Socié (CR16) 2005; 106 Parker (CR18) 2016; 2016 Brodsky (CR31) 2020; 135 Risitano, Marotta, Ricci, Marano, Frieri, Cacace, Sica, Kulasekararaj, Calado, Scheinberg, Notaro, Peffault de Latour (CR13) 2019; 10 Ricklin, Lambris (CR37) 2013; 190 Yamashina, Ueda, Kinoshita, Takami, Ojima, Ono, Tanaka, Kondo, Orii, Okada (CR9) 1990; 323 CR33 Kazmi, Koda, Ndiaye, Visvikis-Siest, Morton, Gaunt, Galea (CR43) 2019; 494 Risitano, Notaro, Marando, Serio, Ranaldi, Seneca, Ricci, Alfinito, Camera, Gianfaldoni, Amendola, Boschetti, Di Bona, Fratellanza, Barbano, Rodeghiero, Zanella, Iori, Selleri, Luzzatto, Rotoli (CR4) 2009; 113 Cella, Lai, Chang, Peterman, Slavin (CR34) 2002; 94 Loschi, Porcher, Barraco, Terriou, Mohty, de Guibert, Mahe, Lemal, Dumas, Etienne, Jardin, Royer, Bordessoule, Rohrlich, Fornecker, Salanoubat, Maury, Cahn, Vincent, Sene, Rigaudeau, Nguyen, Lepretre, Mary, Corront, Socie, Peffault de Latour (CR40) 2016; 91 Morgan, Harris (CR36) 2015; 14 Korkama, Armstrong, Jarva, Meri (CR6) 2018; 9 DeZern, Dorr, Brodsky (CR27) 2013; 90 Froguel, Ndiaye, Bonnefond, Bouatia-Naji, Dechaume, Siest, Herbeth, Falchi, Bottolo, Guéant-Rodriguez, Lecoeur, Langlois, Labrune, Ruokonen, El Shamieh, Stathopoulou, Morandi, Maffeis, Meyre, Delanghe, Jacobson, Sjöström, Carlsson, Walley, Elliott, Jarvelin, Dedoussis, Visvikis-Siest (CR42) 2012; 7 Hillmen, Muus, Dührsen, Risitano, Schubert, Luzzatto, Schrezenmeier, Szer, Brodsky, Hill, Socié, Bessler, Rollins, Bell, Rother, Young (CR39) 2007; 110 McKinley, Richards, Munir, Griffin, Mitchell, Arnold, Riley, Copeland, Newton, Hill, Hillmen (CR23) 2017; 130 Paquette, Yoshimura, Veiseh, Kunkel, Gajewski, Rosen (CR2) 1997; 96 Naryzny, Legina (CR41) 2021; 15 Barcellini, Fattizzo (CR14) 2015; 2015 Bessler, Mason, Hillmen, Miyata, Yamada, Takeda, Luzzatto, Kinoshita (CR1) 1994; 13 Schrezenmeier, Kulasekararaj, Mitchell, Sicre de Fontbrune, Devos, Okamoto, Wells, Rottinghaus, Liu, Ortiz, Lee, Socié (CR46) 2020; 11 de Latour, Mary, Salanoubat, Terriou, Etienne, Mohty, Roth, de Guibert, Maury, Cahn, Socié (CR38) 2008; 112 Hillmen, Szer, Weitz, Röth, Höchsmann, Panse, Usuki, Griffin, Kiladjian, de Castro, Nishimori, Tan, Hamdani, Deschatelets, Francois, Grossi, Ajayi, Risitano, de la Tour (CR45) 2021; 384 Mastellos, Ricklin, Yancopoulou, Risitano, Lambris (CR15) 2014; 7 Hillmen, Young, Schubert, Brodsky, Socié, Muus, Röth, Szer, Elebute, Nakamura, Browne, Risitano, Hill, Schrezenmeier, Fu, Maciejewski, Rollins, Mojcik, Rother, Luzzatto (CR22) 2006; 355 Rother, Bell, Hillmen, Gladwin (CR20) 2005; 293 Schrezenmeier, Röth, Araten, Kanakura, Larratt, Shammo, Wilson, Shayan, Maciejewski (CR21) 2020; 99 Mehdi, Grossi, Deschatelets, Pullon, Tan, Vega, Francois (CR32) 2017; 89 Boccuni, Del Vecchio, Di Noto, Rotoli (CR10) 2000; 33 Ricklin, Hajishengallis, Yang, Lambris (CR12) 2010; 11 Hill, DeZern, Kinoshita, Brodsky (CR3) 2017; 3 Debureaux, Kulasekararaj, Cacace, Silva, Calado, Barone, Sicre de Fontbrune, Prata, Soret, Sica, Notaro, Scheinberg, Mallikarjuna, Gandhi, Large, Risitano, Peffault de Latour, Frieri (CR28) 2021 Hillmen, Bessler, Mason, Watkins, Luzzatto (CR8) 1993; 90 Kulasekararaj, Hill, Rottinghaus, Langemeijer, Wells, Gonzalez-Fernandez, Gaya, Lee, Gutierrez, Piatek, Szer, Risitano, Nakao, Bachman, Shafner, Damokosh, Ortiz, Röth, Peffault de Latour (CR29) 2019; 133 Ninomiya, Sims (CR11) 1992; 267 Nishiyama, Hanaoka (CR44) 2000; 47 Takeda, Miyata, Kawagoe, Iida, Endo, Fujita, Takahashi, Kitani, Kinoshita (CR7) 1993; 73 Hillmen, Muus, Röth, Elebute, Risitano, Schrezenmeier, Szer, Browne, Maciejewski, Schubert, Urbano-Ispizua, de Castro, Socié, Brodsky (CR25) 2013; 162 Brodsky, Peffault de Latour, Rottinghaus, Röth, Risitano, Weitz, Hillmen, Maciejewski, Szer, Lee, Kulasekararaj, Volles, Damokosh, Ortiz, Shafner, Liu, Hill, Schrezenmeier (CR24) 2021; 106 A Hill (4903_CR3) 2017; 3 H Schrezenmeier (4903_CR46) 2020; 11 W Barcellini (4903_CR14) 2015; 2015 PE Debureaux (4903_CR28) 2021 D Ricklin (4903_CR37) 2013; 190 T Nishiyama (4903_CR44) 2000; 47 DC Mastellos (4903_CR15) 2014; 7 H Nakayama (4903_CR26) 2016; 39 RL Paquette (4903_CR2) 1997; 96 P Hillmen (4903_CR45) 2021; 384 CE McKinley (4903_CR23) 2017; 130 P Hillmen (4903_CR22) 2006; 355 P Hillmen (4903_CR8) 1993; 90 ES Korkama (4903_CR6) 2018; 9 M Bessler (4903_CR1) 1994; 13 C Parker (4903_CR16) 2005; 106 RA Brodsky (4903_CR24) 2021; 106 J Takeda (4903_CR7) 1993; 73 P Hillmen (4903_CR25) 2013; 162 AM Risitano (4903_CR17) 2008; 2 CJ Parker (4903_CR18) 2016; 2016 RA Brodsky (4903_CR31) 2020; 135 AE DeZern (4903_CR27) 2013; 90 RP Rother (4903_CR20) 2005; 293 N Kazmi (4903_CR43) 2019; 494 H Schrezenmeier (4903_CR21) 2020; 99 D Mehdi (4903_CR32) 2017; 89 P Froguel (4903_CR42) 2012; 7 P Boccuni (4903_CR10) 2000; 33 M Yamashina (4903_CR9) 1990; 323 H Ninomiya (4903_CR11) 1992; 267 AM Risitano (4903_CR13) 2019; 10 4903_CR33 D Cella (4903_CR34) 2002; 94 P Hillmen (4903_CR39) 2007; 110 SN Naryzny (4903_CR41) 2021; 15 AS Ullman (4903_CR5) 1963; 11 H Schrezenmeier (4903_CR19) 2014; 99 D Cella (4903_CR35) 2002; 24 M Loschi (4903_CR40) 2016; 91 AG Kulasekararaj (4903_CR29) 2019; 133 RP de Latour (4903_CR38) 2008; 112 AM Risitano (4903_CR4) 2009; 113 D Ricklin (4903_CR12) 2010; 11 BP Morgan (4903_CR36) 2015; 14 JW Lee (4903_CR30) 2019; 133
References_xml	– volume: 112 start-page: 3099 issue: 8 year: 2008 end-page: 3106 ident: CR38 article-title: Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories publication-title: Blood doi: 10.1182/blood-2008-01-133918 – volume: 3 start-page: 17028 year: 2017 ident: CR3 article-title: Paroxysmal nocturnal haemoglobinuria publication-title: Nat Rev Dis Primers doi: 10.1038/nrdp.2017.28 – volume: 133 start-page: 540 issue: 6 year: 2019 end-page: 549 ident: CR29 article-title: Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced adult patients with PNH: the 302 study publication-title: Blood doi: 10.1182/blood-2018-09-876805 – volume: 94 start-page: 528 issue: 2 year: 2002 end-page: 538 ident: CR34 article-title: Fatigue in cancer patients compared with fatigue in the general United States population publication-title: Cancer doi: 10.1002/cncr.10245 – volume: 47 start-page: 881 issue: 9 year: 2000 end-page: 885 ident: CR44 article-title: Free hemoglobin concentrations in patients receiving massive blood transfusion during emergency surgery for trauma publication-title: Canadian journal of anaesthesia Journal canadien d'anesthesie doi: 10.1007/bf03019668 – volume: 2016 start-page: 208 issue: 1 year: 2016 end-page: 216 ident: CR18 article-title: Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria publication-title: Hematology doi: 10.1182/asheducation-2016.1.208 – volume: 355 start-page: 1233 issue: 12 year: 2006 end-page: 1243 ident: CR22 article-title: The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria publication-title: N Engl J Med doi: 10.1056/NEJMoa061648 – volume: 11 start-page: 2040620720966137 year: 2020 ident: CR46 article-title: One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study publication-title: Ther Adv Hematol doi: 10.1177/2040620720966137 – volume: 89 start-page: 115 year: 2017 ident: CR32 article-title: APL-2, a complement C3 inhibitor, may potentially reduce both intravascular and extravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria publication-title: Mol Immunol doi: 10.1016/j.molimm.2017.06.039 – volume: 14 start-page: 857 issue: 12 year: 2015 end-page: 877 ident: CR36 article-title: Complement, a target for therapy in inflammatory and degenerative diseases publication-title: Nat Rev Drug Discov doi: 10.1038/nrd4657 – volume: 106 start-page: 3699 issue: 12 year: 2005 end-page: 3709 ident: CR16 article-title: Diagnosis and management of paroxysmal nocturnal hemoglobinuria publication-title: Blood doi: 10.1182/blood-2005-04-1717 – volume: 130 start-page: 3471 issue: Supplement 1 year: 2017 end-page: 3471 ident: CR23 article-title: Extravascular hemolysis due to C3-loading in patients with PNH treated with eculizumab: defining the clinical syndrome publication-title: Blood doi: 10.1182/blood.V130.Suppl_1.3471.3471 – ident: CR33 – volume: 384 start-page: 1028 issue: 11 year: 2021 end-page: 1037 ident: CR45 article-title: Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria publication-title: N Engl J Med doi: 10.1056/NEJMoa2029073 – volume: 99 start-page: 1505 issue: 7 year: 2020 end-page: 1514 ident: CR21 article-title: Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry publication-title: Ann Hematol doi: 10.1007/s00277-020-04052-z – volume: 162 start-page: 62 issue: 1 year: 2013 end-page: 73 ident: CR25 article-title: Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria publication-title: Br J Haematol doi: 10.1111/bjh.12347 – volume: 135 start-page: 884 issue: 12 year: 2020 end-page: 885 ident: CR31 article-title: A complementary new drug for PNH publication-title: Blood doi: 10.1182/blood.2020004959 – volume: 73 start-page: 703 issue: 4 year: 1993 end-page: 711 ident: CR7 article-title: Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria publication-title: Cell doi: 10.1016/0092-8674(93)90250-t – volume: 33 start-page: 25 issue: 1 year: 2000 end-page: 43 ident: CR10 article-title: Glycosyl phosphatidylinositol (GPI)-anchored molecules and the pathogenesis of paroxysmal nocturnal hemoglobinuria publication-title: Crit Rev Oncol Hematol doi: 10.1016/s1040-8428(99)00052-9 – volume: 293 start-page: 1653 issue: 13 year: 2005 end-page: 1662 ident: CR20 article-title: The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease publication-title: JAMA doi: 10.1001/jama.293.13.1653 – volume: 90 start-page: 16 issue: 1 year: 2013 end-page: 24 ident: CR27 article-title: Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria publication-title: Eur J Haematol doi: 10.1111/ejh.12021 – volume: 90 start-page: 5272 issue: 11 year: 1993 end-page: 5276 ident: CR8 article-title: Specific defect in N-acetylglucosamine incorporation in the biosynthesis of the glycosylphosphatidylinositol anchor in cloned cell lines from patients with paroxysmal nocturnal hemoglobinuria publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.90.11.5272 – volume: 494 start-page: 138 year: 2019 end-page: 142 ident: CR43 article-title: Genetic determinants of circulating haptoglobin concentration publication-title: Clinica chimica acta international journal of clinical chemistry doi: 10.1016/j.cca.2019.03.1617 – volume: 11 start-page: 135 issue: 2 year: 1963 end-page: 145 ident: CR5 article-title: Paroxysmal nocturnal hemoglobinuria: report of two cases with atypical features, autopsy findings, and review of pathophysiology publication-title: Henry Ford Hosp Med Bull – volume: 10 start-page: 1157 year: 2019 ident: CR13 article-title: Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT publication-title: Front Immunol doi: 10.3389/fimmu.2019.01157 – volume: 7 issue: 3 year: 2012 ident: CR42 article-title: A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels publication-title: PLoS ONE doi: 10.1371/journal.pone.0032327 – volume: 190 start-page: 3839 issue: 8 year: 2013 end-page: 3847 ident: CR37 article-title: Complement in immune and inflammatory disorders: therapeutic interventions publication-title: J Immunol doi: 10.4049/jimmunol.1203200 – volume: 9 start-page: 1749 year: 2018 ident: CR6 article-title: Spontaneous remission in paroxysmal nocturnal hemoglobinuria-return to health or transition into malignancy? publication-title: Front Immunol doi: 10.3389/fimmu.2018.01749 – volume: 110 start-page: 4123 issue: 12 year: 2007 end-page: 4128 ident: CR39 article-title: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria publication-title: Blood doi: 10.1182/blood-2007-06-095646 – volume: 99 start-page: 922 issue: 5 year: 2014 end-page: 929 ident: CR19 article-title: Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry publication-title: Haematologica doi: 10.3324/haematol.2013.093161 – volume: 133 start-page: 530 issue: 6 year: 2019 end-page: 539 ident: CR30 article-title: Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study publication-title: Blood doi: 10.1182/blood-2018-09-876136 – volume: 96 start-page: 92 issue: 1 year: 1997 end-page: 97 ident: CR2 article-title: Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria publication-title: Br J Haematol doi: 10.1046/j.1365-2141.1997.d01-1984.x – volume: 323 start-page: 1184 issue: 17 year: 1990 end-page: 1189 ident: CR9 article-title: Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria publication-title: N Engl J Med doi: 10.1056/nejm199010253231707 – volume: 39 start-page: 285 issue: 2 year: 2016 end-page: 288 ident: CR26 article-title: Eculizumab dosing intervals longer than 17 days may be associated with greater risk of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria publication-title: Biol Pharm Bull doi: 10.1248/bpb.b15-00703 – volume: 13 start-page: 110 issue: 1 year: 1994 end-page: 117 ident: CR1 article-title: Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene publication-title: EMBO J doi: 10.1002/j.1460-2075.1994.tb06240.x – volume: 7 start-page: 583 issue: 5 year: 2014 end-page: 598 ident: CR15 article-title: Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape publication-title: Expert Rev Hematol doi: 10.1586/17474086.2014.953926 – volume: 15 start-page: 184 issue: 3 year: 2021 end-page: 198 ident: CR41 publication-title: Haptoglobin as a biomarker. Biomedical chemistry doi: 10.1134/s1990750821030069 – year: 2021 ident: CR28 article-title: Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study publication-title: Bone Marrow Transplant doi: 10.1038/s41409-021-01372-0 – volume: 106 start-page: 230 issue: 1 year: 2021 end-page: 237 ident: CR24 article-title: Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria publication-title: Haematologica doi: 10.3324/haematol.2019.236877 – volume: 11 start-page: 785 issue: 9 year: 2010 end-page: 797 ident: CR12 article-title: Complement: a key system for immune surveillance and homeostasis publication-title: Nat Immunol doi: 10.1038/ni.1923 – volume: 91 start-page: 366 issue: 4 year: 2016 end-page: 370 ident: CR40 article-title: Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study publication-title: Am J Hematol doi: 10.1002/ajh.24278 – volume: 113 start-page: 4094 issue: 17 year: 2009 end-page: 4100 ident: CR4 article-title: Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab publication-title: Blood doi: 10.1182/blood-2008-11-189944 – volume: 267 start-page: 13675 issue: 19 year: 1992 end-page: 13680 ident: CR11 article-title: The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the “b” domain of C9 publication-title: J Biol Chem doi: 10.1016/S0021-9258(18)42266-1 – volume: 2015 year: 2015 ident: CR14 article-title: Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia publication-title: Dis Markers doi: 10.1155/2015/635670 – volume: 2 start-page: 205 issue: 2 year: 2008 end-page: 222 ident: CR17 article-title: Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents publication-title: Biologics : targets & therapy doi: 10.2147/btt.s1420 – volume: 24 start-page: 547 issue: 6 year: 2002 end-page: 561 ident: CR35 article-title: Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales publication-title: J Pain Symptom Manage doi: 10.1016/s0885-3924(02)00529-8 – volume: 2015 year: 2015 ident: 4903_CR14 publication-title: Dis Markers doi: 10.1155/2015/635670 – volume: 99 start-page: 1505 issue: 7 year: 2020 ident: 4903_CR21 publication-title: Ann Hematol doi: 10.1007/s00277-020-04052-z – volume: 90 start-page: 16 issue: 1 year: 2013 ident: 4903_CR27 publication-title: Eur J Haematol doi: 10.1111/ejh.12021 – volume: 355 start-page: 1233 issue: 12 year: 2006 ident: 4903_CR22 publication-title: N Engl J Med doi: 10.1056/NEJMoa061648 – volume: 90 start-page: 5272 issue: 11 year: 1993 ident: 4903_CR8 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.90.11.5272 – volume: 24 start-page: 547 issue: 6 year: 2002 ident: 4903_CR35 publication-title: J Pain Symptom Manage doi: 10.1016/s0885-3924(02)00529-8 – volume: 133 start-page: 530 issue: 6 year: 2019 ident: 4903_CR30 publication-title: Blood doi: 10.1182/blood-2018-09-876136 – volume: 15 start-page: 184 issue: 3 year: 2021 ident: 4903_CR41 publication-title: Haptoglobin as a biomarker. Biomedical chemistry doi: 10.1134/s1990750821030069 – volume: 91 start-page: 366 issue: 4 year: 2016 ident: 4903_CR40 publication-title: Am J Hematol doi: 10.1002/ajh.24278 – volume: 162 start-page: 62 issue: 1 year: 2013 ident: 4903_CR25 publication-title: Br J Haematol doi: 10.1111/bjh.12347 – ident: 4903_CR33 doi: 10.1002/ajh.25960 – volume: 9 start-page: 1749 year: 2018 ident: 4903_CR6 publication-title: Front Immunol doi: 10.3389/fimmu.2018.01749 – volume: 10 start-page: 1157 year: 2019 ident: 4903_CR13 publication-title: Front Immunol doi: 10.3389/fimmu.2019.01157 – volume: 190 start-page: 3839 issue: 8 year: 2013 ident: 4903_CR37 publication-title: J Immunol doi: 10.4049/jimmunol.1203200 – volume: 89 start-page: 115 year: 2017 ident: 4903_CR32 publication-title: Mol Immunol doi: 10.1016/j.molimm.2017.06.039 – volume: 7 start-page: 583 issue: 5 year: 2014 ident: 4903_CR15 publication-title: Expert Rev Hematol doi: 10.1586/17474086.2014.953926 – volume: 267 start-page: 13675 issue: 19 year: 1992 ident: 4903_CR11 publication-title: J Biol Chem doi: 10.1016/S0021-9258(18)42266-1 – volume: 113 start-page: 4094 issue: 17 year: 2009 ident: 4903_CR4 publication-title: Blood doi: 10.1182/blood-2008-11-189944 – volume: 323 start-page: 1184 issue: 17 year: 1990 ident: 4903_CR9 publication-title: N Engl J Med doi: 10.1056/nejm199010253231707 – volume: 11 start-page: 204062072096613 year: 2020 ident: 4903_CR46 publication-title: Ther Adv Hematol doi: 10.1177/2040620720966137 – volume: 13 start-page: 110 issue: 1 year: 1994 ident: 4903_CR1 publication-title: EMBO J doi: 10.1002/j.1460-2075.1994.tb06240.x – volume: 3 start-page: 17028 year: 2017 ident: 4903_CR3 publication-title: Nat Rev Dis Primers doi: 10.1038/nrdp.2017.28 – volume: 133 start-page: 540 issue: 6 year: 2019 ident: 4903_CR29 publication-title: Blood doi: 10.1182/blood-2018-09-876805 – volume: 14 start-page: 857 issue: 12 year: 2015 ident: 4903_CR36 publication-title: Nat Rev Drug Discov doi: 10.1038/nrd4657 – volume: 384 start-page: 1028 issue: 11 year: 2021 ident: 4903_CR45 publication-title: N Engl J Med doi: 10.1056/NEJMoa2029073 – volume: 7 issue: 3 year: 2012 ident: 4903_CR42 publication-title: PLoS ONE doi: 10.1371/journal.pone.0032327 – year: 2021 ident: 4903_CR28 publication-title: Bone Marrow Transplant doi: 10.1038/s41409-021-01372-0 – volume: 110 start-page: 4123 issue: 12 year: 2007 ident: 4903_CR39 publication-title: Blood doi: 10.1182/blood-2007-06-095646 – volume: 2016 start-page: 208 issue: 1 year: 2016 ident: 4903_CR18 publication-title: Hematology doi: 10.1182/asheducation-2016.1.208 – volume: 106 start-page: 230 issue: 1 year: 2021 ident: 4903_CR24 publication-title: Haematologica doi: 10.3324/haematol.2019.236877 – volume: 39 start-page: 285 issue: 2 year: 2016 ident: 4903_CR26 publication-title: Biol Pharm Bull doi: 10.1248/bpb.b15-00703 – volume: 494 start-page: 138 year: 2019 ident: 4903_CR43 publication-title: Clinica chimica acta international journal of clinical chemistry doi: 10.1016/j.cca.2019.03.1617 – volume: 11 start-page: 135 issue: 2 year: 1963 ident: 4903_CR5 publication-title: Henry Ford Hosp Med Bull – volume: 73 start-page: 703 issue: 4 year: 1993 ident: 4903_CR7 publication-title: Cell doi: 10.1016/0092-8674(93)90250-t – volume: 99 start-page: 922 issue: 5 year: 2014 ident: 4903_CR19 publication-title: Haematologica doi: 10.3324/haematol.2013.093161 – volume: 293 start-page: 1653 issue: 13 year: 2005 ident: 4903_CR20 publication-title: JAMA doi: 10.1001/jama.293.13.1653 – volume: 33 start-page: 25 issue: 1 year: 2000 ident: 4903_CR10 publication-title: Crit Rev Oncol Hematol doi: 10.1016/s1040-8428(99)00052-9 – volume: 106 start-page: 3699 issue: 12 year: 2005 ident: 4903_CR16 publication-title: Blood doi: 10.1182/blood-2005-04-1717 – volume: 135 start-page: 884 issue: 12 year: 2020 ident: 4903_CR31 publication-title: Blood doi: 10.1182/blood.2020004959 – volume: 47 start-page: 881 issue: 9 year: 2000 ident: 4903_CR44 publication-title: Canadian journal of anaesthesia Journal canadien d'anesthesie doi: 10.1007/bf03019668 – volume: 11 start-page: 785 issue: 9 year: 2010 ident: 4903_CR12 publication-title: Nat Immunol doi: 10.1038/ni.1923 – volume: 2 start-page: 205 issue: 2 year: 2008 ident: 4903_CR17 publication-title: Biologics : targets & therapy doi: 10.2147/btt.s1420 – volume: 130 start-page: 3471 issue: Supplement 1 year: 2017 ident: 4903_CR23 publication-title: Blood doi: 10.1182/blood.V130.Suppl_1.3471.3471 – volume: 94 start-page: 528 issue: 2 year: 2002 ident: 4903_CR34 publication-title: Cancer doi: 10.1002/cncr.10245 – volume: 96 start-page: 92 issue: 1 year: 1997 ident: 4903_CR2 publication-title: Br J Haematol doi: 10.1046/j.1365-2141.1997.d01-1984.x – volume: 112 start-page: 3099 issue: 8 year: 2008 ident: 4903_CR38 publication-title: Blood doi: 10.1182/blood-2008-01-133918
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Snippet	Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors...
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SubjectTerms	Adult Anemia Biomarkers Blood diseases Bone marrow Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Complement Inactivating Agents - adverse effects Dehydrogenases Drug dosages FDA approval Hematology Hemoglobin Hemoglobins Hemoglobinuria, Paroxysmal - drug therapy Hemolysis Hospitals Humans Medicine Medicine & Public Health Monoclonal antibodies Oncology Original Original Article Peptides, Cyclic - adverse effects Pharmaceuticals Quality of life
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Title	Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria
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