180
Views
0
CrossRef citations to date
0
Altmetric
Drug Profile

Pharmacological and clinical profile of ravulizumab 100 mg/mL formulation for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

ORCID Icon
Pages 401-410 | Received 23 Aug 2022, Accepted 27 Apr 2023, Published online: 09 May 2023

References

  • Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1;106(12):3699–3709.
  • Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011 Sep 8;6:60.
  • Parker CJ, Kar S, Kirkpatrick P. Eculizumab. Nat Rev Drug Discov. 2007 Jul;6(7):515–516.
  • Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233–1243.
  • Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169–2181.
  • Hill A, Hillmen P, Richards SJ, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005 Oct 1;106(7):2559–2565.
  • Richards SJ, Hill A, Hillmen P. Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria. Cytometry B Clin Cytom. 2007 Sep;72(5):291–298.
  • Licht C, Greenbaum LA, Muus P, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int. 2015 May;87(5):1061–1073.
  • Greenbaum LA, Fila M, Ardissino G, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016 Mar;89(3):701–711.
  • Zuber J, Frimat M, Caillard S, et al. Use of highly individualized complement blockade has revolutionized clinical outcomes after kidney transplantation and renal epidemiology of atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2019 Dec;30(12):2449–2463.
  • Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (REGAIN): a phase 3, randomized, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017 Dec;16(12):976–986.
  • Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019 Aug 15;381(7):614–625.
  • Werion A, Rondeau E. Application of C5 inhibitors in glomerular diseases in 2021. Kidney Res Clin Pract. 2022 Jul;41(4):412–421.
  • Fakhouri F, Schwotzer N, Golshayan D, et al. The rational use of complement inhibitors in kidney diseases. Kidney Int Rep. 2022 Mar 4;7(6):1165–1178.
  • McKeage K. Ravulizumab: first global approval. Drugs. 2019 Feb;79(3):347–352.
  • Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=125166. [cited 7 Aug 2022]
  • Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/soliris. [cited 7 Aug 2022]
  • de Cordoba SR, Tortajada A, Harris CL, et al. Complement dysregulation and disease: from genes and proteins to diagnostics and drugs. Immunobiology. 2012 Nov;217(11):1034–1046.
  • Campistol JM, Arias M, Ariceta G, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2013 Jan 18;33(1):27–45.
  • Merle NS, Church SE, Fremeaux-Bacchi V, et al. Complement system part I - Molecular mechanisms of activation and regulation. Front Immunol. 2015 Jun 2;6:262.
  • Zipfel PF, Skerka C, Hellwage J, et al. Factor H family proteins: on complement, microbes and human diseases. Biochem Soc Trans. 2002 Nov;30(Pt 6):971–978.
  • Rodriguez de Córdoba S, Goicochea de Jorge E. Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. Clin Exp Immunol. 2008 Jan;151(1):1–13.
  • Loirat C, Noris M, Fremeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2008 Nov;23(11):1957–1972.
  • Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009 Oct 22;361(17):1676–1687.
  • de Córdoba SR. Complement genetics and susceptibility to inflammatory disease. lessons from genotype-phenotype correlations. Immunobiology. 2016 Jun;221(6):709–714.
  • Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9;333(19):1253–1258.
  • Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014 Oct 30;124(18):2804–2811.
  • Hill A, DeZern AE, Kinoshita T, et al. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017 May 18;3:17028.
  • Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Fr Soci Haematol Lancet. 1996 Aug 31;348(9027):573–577.
  • Gulbis B, Eleftheriou A, Angastiniotis M, et al. Epidemiology of rare anaemias in europe. Adv Exp Med Biol. 2010;686:375–396.
  • Curran KJ, Kernan NA, Prockop SE, et al. Paroxysmal nocturnal hemoglobinuria in pediatric patients. Pediatr Blood Cancer. 2012 Sep;59(3):525–529.
  • Urbano-Ispizua Á, Muus P, Schrezenmeier H, et al. Different clinical characteristics of paroxysmal nocturnal hemoglobinuria in pediatric and adult patients. Haematologica. 2017 Mar;102(3):e76–79.
  • Luzzatto L. PNH phenotypes and their genesis. Br J Haematol. 2020;189(5):802–805.
  • Kinoshita T, Fujita M. Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling. J Lipid Res. 2016;57(1):6–24.
  • Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell. 1997;88(1):1–4.
  • Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350(6):552–559.
  • 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(25):6786–6792.
  • Taylor CM, Machin S, Wigmore SJ, et al. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the united kingdom. Br J Haematol. 2010;148(1):37–47.
  • Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: the impact of MCP, CFH, and if mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267–1279.
  • Thurman JM, Renner B. Dynamic control of the complement system by modulated expression of regulatory proteins. Lab Invest. 2011;91(1):4–11.16.
  • Kavanagh D, Goodship TH, Richards A. Atypical hemolytic uremic syndrome. Semin Nephrol. 2013;33:508–530.
  • Fakhouri F, Zuber J, Frémeaux-Bacchi V, et al. Haemolytic uraemic syndrome. Lancet. 2017;390:681–696.
  • Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15–39 24.
  • Goodship TH, Cook HT, Fakhouri F, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a kidney disease: improving global outcomes (KDIGO) controversies conference. Kidney Int. 2017;91:539–551.
  • Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24:687–696.
  • Pérez-Caballero D, González-Rubio C, Gallardo ME, et al. Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome. Am J Hum Genet. 2001;68:478–484 6.
  • Richards A, Buddles MR, Donne RL, et al. Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition. Am J Hum Genet. 2001;68:485–490 7.
  • Richards A, Kemp EJ, Liszewski MK, et al. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2003;100:12966–12971.
  • Noris M, Brioschi S, Caprioli J, et al. Familial haemolytic uraemic syndrome and an MCP mutation. Lancet. 2003;362:1542–1547.
  • Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, et al. Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet. 2004;41:e84.
  • Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2007;104:240–245.
  • Fremeaux-Bacchi V, Miller EC, Liszewski MK, et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood. 2008;112:4948–4952.
  • Dragon-Durey M-A, Loirat C, Cloarec S, et al. Antifactor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16:555–563.
  • Józsi M, Strobel S, Dahse HM, et al. Anti factor H autoantibodies block C terminal recognition function of factor H in hemolytic uremic syndrome. Blood. 2005;110:1516–1518.
  • Abarrategui-Garrido C, Martínez-Barricarte R, López-Trascasa M, et al. Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. Blood. 2009;114(19):4261–4271.
  • Loirat C, Garnier A, Sellier-Leclerc AL, et al. Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost. 2010;36:673–681.
  • Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844–1859.
  • Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide french series comparing children and adults. Clin J Am Soc Nephrol. 2013;8:554–562.
  • Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med. 2009;360:544–546.
  • Loirat C, Saland J, Bitzan M. Management of hemolytic uremic syndrome. Presse Med. 2012;41:e115–135.
  • 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(1):62–73.
  • Fakhouri F, Hourmant M, Campistol JM, et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kidney Dis. 2016 Jul;68(1):84–93.
  • NICE (National Institute for Health and Care Excellence. Eculizumab for treating atypical haemolytic uraemic syndrome NIfHaCE. 2015. Available from: https://www.nice.org.uk/guidance/hst1/resources/eculizumab-fortreating-atypical-haemolytic-uraemic-syndrome.pdf.
  • Zuber J, Le Quintrec M, Krid S, et al. Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant. 2012;12:3337–3354.
  • Schaefer F, Ardissino G, Ariceta G, et al. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int. 2018;94:408–418.
  • Siedlecki AM, Isbel N, Vande Walle J, et al. Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome. Kidney Int Rep. 2018;4(3):434–446.
  • Rondeau E, Cataland SR, Al-Dakkak I, et al. Eculizumab safety: five-year experience from the global atypical hemolytic uremic syndrome registry. Kidney Int Rep. 2019 Aug 2;4(11):1568–1576.
  • Konar M, Granoff DM. Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults. Blood. 2017;130(7):891–899.
  • Benamu E, Montoya J. Infections associated with the use of eculizumab: recommendations for prevention and prophylaxis. Curr Opin Infect Dis. 2016;29:319–329.
  • Socié 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(9):1044–1053.
  • Lee JW, de Latour R P, Brodsky RA, et al. Effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia in the international PNH registry. Am J Hematol. 2019;94(1):E37–41.
  • Menne J, Delmas Y, Fakhouri F, et al. Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study. BMC Nephrol. 2019;20(1):125.
  • Greenbaum LA, Licht C, Nikolaou V, et al. Functional assessment of fatigue and other patient-reported outcomes in patients enrolled in the global aHUS registry. Kidney Int Rep. 2020;5(8):1161–1171.
  • Ross AB, Rouanet E, Murphy AJ, et al. Complications associated with totally implantable access ports in children less than 1 year of age. J Pediatr Surg. 2021;57(10):p. 463–468.
  • Karpman D, Höglund P. Orphan drug policies and use in pediatric nephrology. Pediatr Nephrol. 2017;32(1):1–6.
  • Available from: https://www.fda.gov/media/135113/download. [cited Aug 21, 2022]
  • Available from: https://www.ema.europa.eu/en/documents/product-information/ultomiris-epar-product-informationen.pdf. [cited Aug 21, 2022]
  • Sheridan D, Yu ZX, Zhang Y, et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS ONE. 2018;13(4):e0195909.
  • Ariceta G, Dixon BP, Kim SH, et al. The long-acting C5 inhibitor, ravulizumab, is effective and safe in pediatric patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2021;100(1):225–237.
  • Dixon BP, Sabus A. Ravulizumab 100 mg/mL formulation reduces infusion time and frequency, improving the patient and caregiver experience in the treatment of atypical haemolytic uraemic syndrome. J Clin Pharm Ther. 2022 Jul;47(7):1081–1087.
  • Röth 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(17):2176–2185.
  • Lee JW, Sicre de Fontbrune F, Lee LW, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):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(6):540–549.
  • Brodsky RA, Peffault de Latour R, 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(1):230–237.
  • 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(3):476–485.
  • Peipert JD, Kulasekararaj AG, Gaya A, et al. Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria. PLoS ONE. 2020;15(9):e0237497.
  • 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(3):205–214.
  • Schrezenmeier H, Kulasekararaj A, Mitchell L, et al. 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. Ther Adv Hematol. 2020;11:2040620720966137.
  • O’Connell T, Buessing M, Johnson S, et al. Cost-utility analysis of ravulizumab compared with eculizumab in adult patients with paroxysmal nocturnal hemoglobinuria. Pharmacoeconomics. 2020;38(9):981–994.
  • Tomazos I, Sierra JR, Johnston KM, et al. Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab. Hematology. 2020;25(1):327–334.
  • Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020;97(6):1287–1296.
  • Tomazos I, Hatswell AJ, Cataland S, et al. Comparative efficacy of ravulizumab and eculizumab in the treatment of atypical hemolytic uremic syndrome: an indirect comparison using clinical trial data. Clin Nephrol. 2022;97(5):261–272.
  • Barbour T, Scully M, Ariceta G, et al. Long-term efficacy and safety of the long-acting complement C5 inhibitor ravulizumab for the treatment of atypical hemolytic uremic syndrome in adults. Kidney Int Rep. 2021 24;6(6):1603–1613.
  • Tanaka K, Adams B, Aris AM, et al. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021;36(4):889–898.
  • Wang Y, Johnston K, Popoff E, et al. A US cost-minimization model comparing ravulizumab versus eculizumab for the treatment of atypical hemolytic uremic syndrome. J Med Econ. 2020;23(12):1503–1515.
  • Levy AR, Chen P, Johnston K, et al. Quantifying the economic effects of ravulizumab versus eculizumab treatment in patients with atypical hemolytic uremic syndrome. J Med Econ. 2022;25(1):249–259.
  • Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2021;137(10):1304–1309.
  • 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(8):3359–3363.
  • Ariceta G. Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (Ahus)-a question to be addressed in a scientific way. Pediatr Nephrol. 2019;34(5):943–949.
  • Ariceta G, Fakhouri F, Sartz L, et al. Eculizumab discontinuation in atypical haemolytic uraemic syndrome: tMA recurrence risk and renal outcomes. Clin Kidney J. 2021;14(9):2075–2084.
  • Legendre C, Rebecca-Sberro S, Zuber J. Ravulizumab for the treatment of aHUS in adults: improving quality of life. Kidney Int Rep. 2021 12;6(6):1489–1491.
  • Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028–1037.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.