Complement inhibitor therapy should be available to patients with paroxysmal nocturnal hemoglobinuria throughout the world

Wintrobe M. Clinical hematology. Baltimore: Lea and Febiger; 1946.

Google Scholar 

Dacie J. Paroxysmal nocturnal haemoglobinuria. In: The haemolytic anaemias. 3 Ed. London: Churchill Livingston; 1999. p. 139–330.

Google Scholar 

Hillmen P, Hall C, Marsh Jc, Elebute M, Bombara Mp, Petro Be et al. 2004 Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. New Eng J Med 350 (6):552–9.

Hillmen P, Young Ns, Schubert J, Brodsky Ra, Socie G, Muus P et al. 2006 The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. New Eng J Med. 355 (12):1233–43.

Hill A, Rother Rp, Arnold L, Kelly R, Cullen Mj, Richards Sj et al. 2010 Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica. 95(4):567–73. https://doi.org/10.3324/Haematol.2009.007229.

Risitano Am, Notaro R, Marando L, Serio B, Ranaldi D, Seneca E et al. 2009 Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 113 (17):4094–100. https://doi.org/10.1182/Blood-2008-11-189944.

Luzzatto L, Risitano AM, Notaro R. Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica. 2010;95(4):523–6. https://doi.org/10.3324/Haematol.2009.01784895/4/523[Pii].

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luzzatto L, Gianfaldoni G, Notaro R. Management of paroxysmal nocturnal haemoglobinuria: A personal view. Br J Haematol. 2011;153(6):709–20. https://doi.org/10.1111/J.1365-2141.2011.08690.X.

Article  PubMed  Google Scholar 

Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384(11):1028–37. https://doi.org/10.1056/Nejmoa2029073.

Article  CAS  PubMed  Google Scholar 

Peffault De Latour R, Röth A, Kulasekararaj A, Han B, Scheinberg P, Maciejewski J, et al. Oral iptacopan monotherapy in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2024;390(11):994–1008. https://doi.org/10.1056/Nejmoa2308695.

Article  CAS  PubMed  Google Scholar 

Lee J, Griffin M, Kim J, Lee Lee L, Piatek C, Nishimura J, et al. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (Alpha): a double-blind, randomised, phase 3 trial. Lancet Haematol. 2023;10(12):E955–65. https://doi.org/10.1016/S2352-3026(23)00315-0.

Article  CAS  PubMed  Google Scholar 

Gavriilaki E, De Latour RP, Risitano AM. 2022 Advancing therapeutic complement inhibition in hematologic diseases: Pnh And Beyond. Blood.139(25):3571–82. https://doi.org/10.1182/Blood.2021012860.

Notaro R, Luzzatto L. Breakthrough hemolysis in PNH with proximal or terminal complement inhibition. N Engl J Med. 2022;387(2):160–6. https://doi.org/10.1056/Nejmra2201664.

Article  CAS  PubMed  Google Scholar 

Zhang L, Yang C, Yue C, Ma J, He C, Tsui P, et al. Kp104, a bifunctional C5 Mab–factor H fusion protein, demonstrates sustained long-term efficacy and safety in complement inhibitor–naïve Pnh patients: 2-year results from a phase 2 study with 8-week post-treatment safety follow-up. Blood. 2025;146(Supplement 1):1118. https://doi.org/10.1182/Blood-2025-1118.

Article  Google Scholar 

Gulbis B, Eleftheriou A, Angastiniotis M, Ball S, Surralles J, Castella M, et al. Epidemiology of rare anaemias in Europe. Adv Exp Med Biol. 2010;686:375–96. https://doi.org/10.1007/978-90-481-9485-8_22.

Article  PubMed  Google Scholar 

Michaeli T, Jurges H, Michaeli D. Fda approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications: cross sectional analysis. BMJ. 2023;381:E073242. https://doi.org/10.1136/Bmj-2022-073242.

Article  PubMed  PubMed Central  Google Scholar 

Luzzatto L. Management of paroxysmal nocturnal hemoglobinuria (PNH). J Clin Lab Anal. 2022;36(12):E24770. https://doi.org/10.1002/Jcla.24770.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luzzatto L, Hyry H, Schieppati A, Costa E, Simoens S, Schaefer F, et al. Outrageous prices of orphan drugs: a call for collaboration. Lancet. 2018;392:791–4. https://doi.org/10.1016/S0140-6736(18)31069-9.

Article  PubMed  Google Scholar 

Costa E, Cappellini Md, Rivella S, Chilin A, Alessi E, Riccaboni M et al. 2022 Emergent treatments for beta-thalassemia and orphan drug legislations. Drug Discov Today. 27 (11):103342. https://doi.org/10.1016/J.Drudis.2022.103342

Kulasekararaj A, Lanza F, Arvanitakis A, Langemeijer S, Chonat S, Tombak A, et al. Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024;99(11):2108–17. https://doi.org/10.1002/Ajh.27456.

Article  CAS  PubMed  Google Scholar 

Jang J, Tomuleasa C, Oliynyk H, Lanamtieng T, Park J, Kim Y, et al. Epysqli (SB12; biosimilar to reference eculizumab) in Asian and non-Asian patients with paroxysmal nocturnal hemoglobinuria: subgroup analysis of a global phase III randomized controlled trial. EJHaem. 2025;6(2):E70020. https://doi.org/10.1002/Jha2.70020.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kulagin A, Ptushkin V, Lukina E, Davydkin I, Korobkin A, Konstantinova T, et al. Results of long-term therapy with a biosimilar of eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Acta Haematol. 2025;148(4):443–51. https://doi.org/10.1159/000542294.

Article  CAS  PubMed  Google Scholar 

Stevens A, Jensen J, Wyller K, Kilgore P, Chatterjee S, Rohrbaugh M. The role of public-sector research in the discovery of drugs and vaccines. N Engl J Med. 2011;364(6):535–41. https://doi.org/10.1056/Nejmsa1008268.

Article  CAS  PubMed  Google Scholar 

Luzzatto L. Paroxysmal nocturnal haemoglobinuria. In: Warrel D, Cox T, Firth J, editors. Oxford textbook of medicine. 5th Ed. Oxford (Uk): Oxford University Press; 2010. p. 4298–302.

Chapter  Google Scholar 

Saso R, Marsh J, Cevreska L, Szer J, Gale Rp, Rowlings Pa et al. 1999 Bone marrow transplants for paroxysmal nocturnal haemoglobinuria. Br J Haematol. 104 (2):392–6. https://doi.org/10.1046/J.1365-2141.1999.01195.X.

Yilmaz F, Soyer N, Cengiz Seval G, Civriz Bozdag S, Topcuoglu P, Unal A, et al. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria with or without aplastic anemia: A multicenter Turkish experience. Turk J Haematol. 2021;38(3):195–203. https://doi.org/10.4274/Tjh.Galenos.2021.2021.0105.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu Y, Zhao Y, Xiong M, Sun R, Cao X, Wei Z, et al. Unmanipulated haploidentical donor and matched unrelated donor hematopoietic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria: a single-center study. Leuk Lymphoma. 2022;63(5):1211–9. https://doi.org/10.1080/10428194.2021.2015588.

Article  CAS  PubMed  Google Scholar 

Yousefi M, Jalilian H, Heydari S, Seyednejad F, Mir N. Cost of lung cancer: a systematic review. Value Health Reg Issues. 2023;33:17–26. https://doi.org/10.1016/J.Vhri.2022.07.007.

Article  PubMed  Google Scholar 

Bhimani N, Wong G, Molloy C, Pavlakis N, Diakos C, Clarke S, et al. Cost of treating metastatic colorectal cancer: a systematic review. Public Health. 2022;211:97–104. https://doi.org/10.1016/J.Puhe.2022.06.022.

Article  CAS  PubMed  Google Scholar 

Webmd. The Costs Of Breast Cancer. 2026. https://www.webmd.com/breast-cancer/breast-cancer-costs. Accessed June 1st 2026.

The L. the global fund and the future of global health. Lancet. 2025;406(10519):2509. https://doi.org/10.1016/S0140-6736(25)02421-3.

Article  Google Scholar 

Hillmen P, Horneff R, Yeh M, Kolev M, Deschatelets P. Navigating the complement pathway to optimize PNH treatment with pegcetacoplan and other currently approved complement inhibitors. Int J Mol Sci. 2024. https://doi.org/10.3390/Ijms25179477.

Article  PubMed  PubMed Central  Google Scholar 

Schmidt C, Hochsmann B, Schrezenmeier H. The complement model disease paroxysmal nocturnal hemoglobinuria. Eur J Immunol. 2024;54(11):E2350817. https://doi.org/10.1002/Eji.202350817.

Article  PubMed  Google Scholar 

Luzzatto L, Makani J. Treating rare diseases in Africa: the drugs exist but the need is unmet. Front Pharmacol. 2021;12:770640. https://doi.org/10.3389/Fphar.2021.770640.

Article  CAS  PubMed  Google Scholar 

Makani J, Cavazzana M, Gupta K, Nnodu O, Odame I, Tshilolo L, et al. Blood diseases in Africa: redressing unjust disparities is an urgent unmet need. Am J Hematol. 2022;97(12):1505–6. https://doi.org/10.1002/Ajh.26754.

Article  PubMed  Google Scholar 

The Max Foundation. The max foundation (Max) expands collaboration with novartis to include access to innovative treatment for paroxysmal nocturnal hemoglobinuria (Pnh). 2026. https://themaxfoundation.org/news/the-max-foundation-expands-collaboration-with-novartis/. Accessed June 1st 2026.

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