Paroxysmal nocturnal hemoglobinuria: Where we stand.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
26
12
2022
received:
19
10
2022
accepted:
27
12
2022
medline:
3
4
2023
pubmed:
4
1
2023
entrez:
3
1
2023
Statut:
ppublish
Résumé
For the last 20 years, therapy of paroxysmal nocturnal hemoglobinuria (PNH) relied-up until recently-on antibody based terminal complement inhibitionon. PNH pathophysiology-a mutational defect leading to partial or complete absence of complement-regulatory proteins on blood cells-leads to intravascular hemolysis and consequences such as thrombosis and other sequelae. A plethora of new drugs interfering with the proximal and terminal complement cascade are under recent development and the first "proof-of-pinciple" proximal complement inhibitor targeting C3 has been approved in 2021. "PNH: where we stand" will try to give a brief account on where we came from and where we stand focusing on approved therapeutic options. The associated improvements as well as potential consequences of actual and future treatments as well as their impact on the disease will continue to necessitate academic and scientific focus on improving treatment options as well as on side effects and outcomes relevant to individual patient lives and circumstances in order to develop effective, safe, and available treatment for all hemolytic PNH patients globally.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Complement Inactivating Agents
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
S20-S32Informations de copyright
© 2023 The Author. American Journal of Hematology published by Wiley Periodicals LLC.
Références
Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017;3:17028.
Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25:1256-1264.
Risitano AM, Notaro R, Luzzatto L, Hill A, Kelly R, Hillmen P. Paroxysmal nocturnal hemoglobinuria-hemolysis before and after eculizumab. N Engl J Med. 2010;363:2270-2272.
McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs. 2011;71:2327-2345.
Parker CJ. Management of paroxysmal nocturnal hemoglobinuria in the era of complement inhibitory therapy. Hematology Am Soc Hematol Educ Program. 2011;2011:21-29.
Risitano AM. Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. Immunobiology. 2012;217:1080-1087.
Schrezenmeier H, Hochsmann B. Drugs that inhibit complement. Transfus Apher Sci. 2012;46:87-92.
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121:4985-4996.
Risitano AM. Anti-complement treatment in paroxysmal nocturnal hemoglobinuria: where we stand and where we are going. Transl Med UniSa. 2014;8:43-52.
Risitano AM, Marotta S. Therapeutic complement inhibition in complement-mediated hemolytic anemias: past, present and future. Semin Immunol. 2016;28:223-240.
Sicre de Fontbrune F, Peffault de Latour R. Ten years of clinical experience with eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Semin Hematol. 2018;55:124-129.
Gavriilaki E, de Latour RP, Risitano AM. Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond. Blood. 2022;139:3571-3582.
Pouw RB, Ricklin D. Tipping the balance: intricate roles of the complement system in disease and therapy. Semin Immunopathol. 2021;43:757-771.
Garred P, Tenner AJ, Mollnes TE. Therapeutic targeting of the complement system: from rare diseases to pandemics. Pharmacol Rev. 2021;73:792-827.
Gerber GF, Brodsky RA. Pegcetacoplan for paroxysmal nocturnal hemoglobinuria. Blood. 2022;139:3361-3365.
Risitano AM, Peffault de Latour R. How we('ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future. Br J Haematol. 2022;196:288-303.
Kulasekararaj AG, Brodsky RA, Nishimura JI, Patriquin CJ, Schrezenmeier H. The importance of terminal complement inhibition in paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2022;13:20406207221091046.
Peffault de Latour R, Hosokawa K, Risitano AM. Hemolytic paroxysmal nocturnal hemoglobinuria: 20 years of medical progress. Semin Hematol. 2022;59:38-46.
Richards SJ, Painter D, Dickinson AJ, et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: a retrospective analysis of the UK's population-based haematological malignancy research network 2004-2018. Eur J Haematol. 2021;107:211-218.
Mustjoki S, Young NS. Somatic mutations in “benign” disease. N Engl J Med. 2021;384:2039-2052.
Schultz DR. Erythrocyte membrane protein deficiencies in paroxysmal nocturnal hemoglobinuria. Am J Med. 1989;87:22N-29N.
Hidaka M, Nagakura S, Horikawa K, et al. Impaired glycosylation of glycosylphosphatidylinositol-anchor synthesis in paroxysmal nocturnal hemoglobinuria leucocytes. Biochem Biophys Res Commun. 1993;191:571-579.
Kinoshita T. Biosynthesis and deficiencies of glycosylphosphatidylinositol. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90:130-143.
Takeda J, Miyata T, Kawagoe K, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73:703-711.
Colden MA, Kumar S, Munkhbileg B, Babushok DV. Insights into the emergence of paroxysmal nocturnal hemoglobinuria. Front Immunol. 2021;12:830172.
Visconte V, Maciejewski JP. Clonal dynamics of hematopoietic stem cell compartment in aplastic anemia. Semin Hematol. 2022;59:47-53.
Hyde R, Dobrovolny D. Orphan drug pricing and payer management in the United States: are we approaching the tipping point? Am Health Drug Benefits. 2010;3:15-23.
Ter Avest M, Langemeijer SMC, Schols SEM, et al. The potential of individualized dosing of ravulizumab to improve patient-friendliness of paroxysmal nocturnal haemoglobinuria treatment at reduced costs. Br J Clin Pharmacol. 2021;87:3359-3363.
Coyle D, Cheung MC, Evans GA. Opportunity cost of funding drugs for rare diseases: the cost-effectiveness of eculizumab in paroxysmal nocturnal hemoglobinuria. Med Decis Making. 2014;34:1016-1029.
Zalman LS, Wood LM, Frank MM, Muller-Eberhard HJ. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria. J Exp Med. 1987;165:572-577.
Kinoshita T, Medof ME, Silber R, Nussenzweig V. Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med. 1985;162:75-92.
Parker CJ. The pathophysiology of paroxysmal nocturnal hemoglobinuria. Exp Hematol. 2007;35:523-533.
Dezern AE, Borowitz MJ. ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 1-clinical utility. Cytometry B Clin Cytom. 2018;94:16-22.
Okoye HC, Efobi CC, Korubo K. Evaluation of laboratory investigative methods of diagnosing clonal hematological disorders in a resource-poor setting. Niger J Clin Pract. 2020;23:33-40.
Jahangirpour M, Vahedi A, Baghdadi H, et al. Paroxysmal nocturnal haemoglobinuria, diagnosis and haematological findings, first report from Iran, model for developing countries. EJHaem. 2022;3:335-340.
Groth M, Singer S, Niedeggen C, et al. Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II. Ann Hematol. 2017;96:171-181.
de Azambuja AP, Oliveira MM, Bitencourt MA, Bonfim C, Malvezzi M, Pasquini R. Analysis of baseline characteristics, disease burden and long-term follow-up of 167 patients with paroxysmal nocturnal hemoglobinuria at a single center in Brazil. Blood Cells Mol Dis. 2021;92:102605.
Fattizzo B, Serpenti F, Giannotta JA, Barcellini W. Difficult cases of paroxysmal nocturnal hemoglobinuria: diagnosis and therapeutic novelties. J Clin Med. 2021;10:948.
Cannizzo E, Raia M, Stefania De Propris M, et al. Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study. Ann Hematol. 2019;98:1083-1093.
Babushok DV. When does a PNH clone have clinical significance? Hematology Am Soc Hematol Educ Program. 2021;2021:143-152.
Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-3709.
Narita A, Miwata S, Imaya M, et al. Minor PNH clones do not distinguish inherited bone marrow failure syndromes from immune-mediated aplastic anemia. Blood Adv. 2022;6:2517-2519.
DeZern AE, Churpek JE. Approach to the diagnosis of aplastic anemia. Blood Adv. 2021;5:2660-2671.
de Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112:3099-3106.
Richards SJ, Dickinson AJ, Cullen MJ, et al. Presentation clinical, haematological and immunophenotypic features of 1081 patients with GPI-deficient (paroxysmal nocturnal haemoglobinuria) cells detected by flow cytometry. Br J Haematol. 2020;189:954-966.
Amara U, Flierl MA, Rittirsch D, et al. Molecular intercommunication between the complement and coagulation systems. J Immunol. 2010;185:5628-5636.
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.
Schrezenmeier H, Röth A, Araten DJ, et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the international PNH registry. Ann Hematol. 2020;99:1505-1514.
Kokoris SI, Gavriilaki E, Miari A, et al. Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features, pathophysiology and treatment. Hematology. 2018;23:558-566.
Hill A, Sapsford RJ, Scally A, et al. Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J Haematol. 2012;158:409-414.
Hoekstra J, Leebeek FWG, Plessier A, et al. Paroxysmal nocturnal hemoglobinuria in Budd-Chiari syndrome: findings from a cohort study. J Hepatol. 2009;51:696-706.
Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117:6786-6792.
Socie G, Schrezenmeier H, Muus P, et al. Changing prognosis in paroxysmal nocturnal haemoglobinuria disease subcategories: an analysis of the international PNH registry. Intern Med J. 2016;46:1044-1053.
Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2009;113:6522-6527.
Hill A, Hillmen P, Richards SJ, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:2559-2565.
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243.
Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111:1840-1847.
Lee JW, Sicre de Fontbrune F, Lee Lee LW, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133:530-539.
Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133:540-549.
Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384:1028-1037.
Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110:4123-4128.
Meyers G, Parker CJ. Management issues in paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2003;77:125-132.
Matos-Fernandez NA, Abou Mourad YR, Caceres W, Kharfan-Dabaja MA. Current status of allogeneic hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Biol Blood Marrow Transplant. 2009;15:656-661.
Cooper JP, Farah RJ, Stevenson PA, Gooley TA, Storb R, Scott BL. Hematopoietic cell transplantation for paroxysmal nocturnal hemoglobinuria in the age of eculizumab. Biol Blood Marrow Transplant. 2019;25:1331-1339.
Nakamura Y, Takenaka K, Yamazaki H, et al. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2021;113:122-127.
Marotta S, Pagliuca S, Risitano AM. Hematopoietic stem cell transplantation for aplastic anemia and paroxysmal nocturnal hemoglobinuria: current evidence and recommendations. Expert Rev Hematol. 2014;7:775-789.
Peffault de Latour R, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012;97:1666-1673.
Socie G, Caby-Tosi M-P, Marantz JL, et al. Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis. Br J Haematol. 2019;185:297-310.
Loschi M, Porcher R, Barraco F, et al. Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol. 2016;91:366-370.
Hillmen P, Muus P, Röth A, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162:62-73.
McNamara LA, Topaz N, Wang X, Hariri S, Fox L, MacNeil JR. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66:734-737.
International PNH Interest Group.
Schrezenmeier H, Muus P, Socié G, et al. Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry. Haematologica. 2014;99:922-999.
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage. 1997;13:63-74.
Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94:528-538.
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365-376.
Fayers P, Bottomley A, EORTC Quality of Life Group; Quality of Life Unit. Quality of life research within the EORTC-the EORTC QLQ-C30. European Organisation for Research and Treatment of Cancer. Eur J Cancer. 2002;38(suppl 4):S125-S133.
Fattizzo B, Cavallaro F, Oliva EN, Barcellini W. Managing fatigue in patients with paroxysmal nocturnal hemoglobinuria: a patient-focused perspective. J Blood Med. 2022;13:327-335.
Dingli D, Matos JE, Lehrhaupt K, et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Ann Hematol. 2022;101:251-263.
Kelly RJ, Höchsmann B, Szer J, et al. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2015;373:1032-1039.
Solal-Celigny P, Tertian G, Fernandez H, et al. Pregnancy and paroxysmal nocturnal hemoglobinuria. Arch Intern Med. 1988;148:593-595.
Manning JE, Anderson RM, Hill A, Zeidan D, Ciantar E. Pregnancy outcomes in women receiving eculizumab for the management of paroxysmal nocturnal haemoglobinuria. Obstet Med. 2022;15:45-49.
Luzzatto L, Gianfaldoni G, Notaro R. Management of paroxysmal nocturnal haemoglobinuria: a personal view. Br J Haematol. 2011;153:709-720.
Risitano AM, Marotta S, Ricci P, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
Debureaux PE, Kulasekararaj AG, Cacace F, et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant. 2021;56:2600-2602.
Nishimura J, Yamamoto M, Hayashi S, et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014;370:632-639.
Peffault de Latour R, Brodsky RA, Ortiz S, et al. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020;191:476-485.
Peffault de Latour R, Fremeaux-Bacchi V, Porcher R, et al. Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Blood. 2015;125:775-783.
Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113:4094-4100.
Rawal N, Pangburn MK. Formation of high affinity C5 convertase of the classical pathway of complement. J Biol Chem. 2003;278:38476-38483.
Harder MJ, Kuhn N, Schrezenmeier H, et al. Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood. 2017;129:970-980.
Mannes M, Dopler A, Zolk O, et al. Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. Blood. 2021;137:443-455.
Lin Z, Schmidt CQ, Koutsogiannaki S, et al. Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria. Blood. 2015;126:891-894.
Notaro R, Luzzatto L. Breakthrough hemolysis in PNH with proximal or terminal complement inhibition. N Engl J Med. 2022;387:160-166.
Wong RSM. Safety and efficacy of pegcetacoplan in paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2022;13:20406207221114673.
Gurnari C, Pagliuca S, Prata PH, et al. Clinical and molecular determinants of clonal evolution in aplastic anemia and paroxysmal nocturnal hemoglobinuria. J Clin Oncol. 2023;41:132-142.
Sun L, Babushok DV. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood. 2020;136:36-49.
Yankeelov TE, Mankoff DA, Schwartz LH, et al. Quantitative imaging in cancer clinical trials. Clin Cancer Res. 2016;22:284-290.
Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108:2509-2519.
Jager U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the first international consensus meeting. Blood Rev. 2020;41:100648.
Risitano A, Wong RS, Al-Adhami M, Chen C, Peffault De Latour R. Categorized hematologic response to Pegcetacoplan and correlations with quality of life in patients with paroxysmal nocturnal hemoglobinuria: post hoc analysis of data from phase 1b, phase 2a, and phase 3 trials. Blood. 2021;138:1104.
Sheridan D, Yu Z-X, Zhang Y, et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS One. 2018;13:e0195909.
Roth A, Rottinghaus ST, Hill A, et al. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018;2:2176-2185.
Kulasekararaj AG, Griffin M, Langemeijer S, et al. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. Eur J Haematol. 2022;109:205-214.
Brodsky RA, de Latour RP, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021;106:230-237.
Fattizzo B, Kulasekararaj AG. Second-generation C5 inhibitors for paroxysmal nocturnal hemoglobinuria. BioDrugs. 2020;34:149-158.
Kulagin AD, Ptushkin VV, Lukina EA, et al. Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab. Ann Hematol. 2021;100:2689-2698.
Roth A, Nishimura J-I, Nagy Z, et al. The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria. Blood. 2020;135:912-920.
Nishimura JI, Usuki K, Ramos J, et al. Crovalimab for treatment of patients with paroxysmal nocturnal haemoglobinuria and complement C5 polymorphism: subanalysis of the phase 1/2 COMPOSER study. Br J Haematol. 2022;198:e46-e50.
Karczewski KJ, Francioli LC, Tiao G, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434-443.
Fukuzawa T, Sampei Z, Haraya K, et al. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. Sci Rep. 2017;7:1080.
Brodsky RA. A complementary new drug for PNH. Blood. 2020;135:884-885.
Risitano AM. Current and future pharmacologic complement inhibitors. Hematol Oncol Clin North Am. 2015;29:561-582.
Kolev M, Barbour T, Baver S, Francois C, Deschatelets P. With complements: C3 inhibition in the clinic. Immunol Rev. 2022;1-18. doi:10.1111/imr.13138.
Lamers C, Xue X, Smieško M, et al. Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors. Nat Commun. 2022;13:5519.
Morikis D, Assa-Munt N, Sahu A, Lambris JD. Solution structure of Compstatin, a potent complement inhibitor. Protein Sci. 1998;7:619-627.
de Castro C, Grossi F, Weitz IC, et al. C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab. Am J Hematol. 2020;95:1334-1343.
de Latour RP, Szer J, Weitz IC, et al. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022;9:e648-e659.
Cella D, Sarda SP, Hsieh R, et al. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. 2022;101:1905-1914.
Wong RSM, Pullon HWH, Amine I, et al. Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2022;101:1971-1986.
Weitz I, Al-Adhami M, Min J, et al. Patients with paroxysmal nocturnal hemoglobinuria treated with pegcetacoplan show improvements in D-dimer normalization and decrease in incidence of thrombosis. Hemasphere. 2022;6:733-734.
Risitano AM, Röth A, Soret J, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021;8:e344-e354.
Kulasekararaj AG, Risitano AM, Maciejewski JP, et al. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021;138:1928-1938.
Griffin M, Muus P, Munir T, et al. Paroxysmal nocturnal hemoglobinuria: experience of compassionate use pegcetacoplan. Blood. 2023;141:116-120.
Griffin M, Kelly R, Pike A. A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going? Ther Adv Rare Dis. 2020;1:2633004020959349.
Jalink M, de Boer ECW, Evers D, et al. Halting targeted and collateral damage to red blood cells by the complement system. Semin Immunopathol. 2021;43:799-816.
Anampa-Guzman A, Freeman-Daily J, Fisch M, et al. The rise of the expert patient in cancer: from backseat passenger to co-navigator. JCO Oncol Pract. 2022;18:578-583.
Kersting C, Kneer M, Barzel A. Patient-relevant outcomes: what are we talking about? A scoping review to improve conceptual clarity. BMC Health Serv Res. 2020;20:596.
Kulasekararaj A, Glasmacher A, Liu P, et al. Composite endpoint to evaluate complement inhibition therapy in patients with paroxysmal nocturnal hemoglobinuria. Eur J Haematol. 2022;108:391-402.
Calvert MJ, Rivera SC, Retzer A, et al. Patient reported outcome assessment must be inclusive and equitable. Nat Med. 2022;28:1120-1124.
Goswami P, Khatib Y, Salek S. Haematological malignancy: are we measuring what is important to patients? A systematic review of quality-of-life instruments. Eur J Haematol. 2019;102:279-311.
Cartmell KB, Bonilha HS, Simpson KN, et al. Patient barriers to cancer clinical trial participation and navigator activities to assist. Adv Cancer Res. 2020;146:139-166.
Nipp RD, Hong K, Paskett ED. Overcoming barriers to clinical trial enrollment. Am Soc Clin Oncol Educ Book. 2019;39:105-114.
Gaya A. Pegcetacoplan: climbing up the complement cascade. Lancet Haematol. 2022;9:e628-e629.
Gusarova V, Degterev M, Lyagoskin I, et al. Analytical and functional similarity of biosimilar Elizaria® with eculizumab reference product. J Pharm Biomed Anal. 2022;220:115004.
Luzzatto L, Hyry HI, Schieppati A, et al. Outrageous prices of orphan drugs: a call for collaboration. Lancet. 2018;392:791-794.
Prasad V, Mailankody S. Research and development spending to bring a single cancer drug to market and revenues after approval. JAMA Intern Med. 2017;177:1569-1575.
Luzzatto L. Control of hemolysis in patients with PNH. Blood. 2021;138:1908-1910.
EuroBloodNet.