The cost–effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by hemolytic anemia, bone marrow failure and thrombosis. We evaluated, the cost–effectiveness of pegcetacoplan, a novel proximal C3 inhibitor, versus ravulizumab in patients with PNH and hemoglobin levels <10.5 g/dl despite eculizumab treatment in the UK healthcare and social services setting. Materials & methods: A Markov cohort framework model, based on the data from the pivotal trial of pegcetacoplan (PEGASUS/NCT03500549), evaluated lifetime costs and outcomes. Patients transitioned through 3 PNH hemoglobin level/red blood cell transfusion health states. Results: Pegcetacoplan provides lower lifetime costs/greater quality-adjusted life years (£6,409,166/14.694QALYs, respectively) versus ravulizumab (£6,660,676/12.942QALYs). Conclusion: Pegcetacoplan is associated with enhanced anemia control, greater QALYs and reduced healthcare costs versus ravulizumab in the UK healthcare and social services setting.
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References
Papers of special note have been highlighted as: • of interest
1.
Hill A, Dezern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Nat. Rev. Dis. Primers 3, 17028 (2017).
2.
Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology Am. Soc. Hematol. Educ. Program 2016(1), 208–216 (2016).
3.
Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: patient journey and burden of disease. J. Manag. Care Spec. Pharm. 26(Suppl. 12-b), S8–S14 (2020).
• Revealed that most of the negative health effects and costs associated with paroxysmal nocturnal hemoglobinuria are due to blood transfusions, a key assumption to the present analysis.
4.
Lee SC, Abdel-Wahab O. The mutational landscape of paroxysmal nocturnal hemoglobinuria revealed: new insights into clonal dominance. J. Clin. Invest. 124(10), 4227–4230 (2014).
5.
Mon Pere N, Lenaerts T, Pacheco JM, Dingli D. Evolutionary dynamics of paroxysmal nocturnal hemoglobinuria. PLOS Comput. Biol. 14(6), e1006133 (2018).
6.
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 73(4), 703–711 (1993).
7.
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. 10, 1157 (2019).
8.
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 333(19), 1253–1258 (1995).
9.
Cheng WY, Sarda SP, Mody-Patel N et al. Real-World healthcare resource utilization (HRU) and costs of patients with paroxysmal nocturnal hemoglobinuria (PNH) receiving eculizumab in a US population. Adv. Ther. 38(8), 4461–4479 (2021).
10.
Socié G, Schrezenmeier H, Muus P et al. Changing prognosis in paroxysmal nocturnal hemoglobinuria disease subcategories: an analysis of the International PNH Registry. Intern Med. J. 46(9), 1044–1053 (2016).
11.
Yu F, Du Y, Han B. A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America. Int. J. Hematol. 103(6), 649–654 (2016).
12.
Orphanet. Paroxysmal nocturnal hemoglobinuria [Internet]. Orphanet J. Rare Dis. (2021). www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=447
13.
Fu R, Li L, Li L et al. Analysis of clinical characteristics of 92 patients with paroxysmal nocturnal hemoglobinuria: a single institution experience in China. J. Clin. Lab Anal. 34(1), e23008 (2020).
14.
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 121(25), 4985–4996; quiz 5105 (2013).
15.
Tomazos I, Sierra JR, Johnston KM, Cheung A, Brodsky RA, Weitz IC. Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab. Hematology 25(1), 327–334 (2020).
16.
Single technology appraisal: ravulizumab for treating paroxysmal nocturnal hemoglobinuria [ID1457] (29 September). www.nice.org.uk/guidance/ta698/evidence/committee-papers-pdf-9132078637
• Allowed assumptions of present analysis to be made on precedent health technology assessment assessments.
17.
Berentsen S, Hill A, Hill QA, Tvedt THA, Michel M. Novel insights into the treatment of complement-mediated hemolytic anemias. Ther. Adv. Hematol. 10, 2040620719873321 (2019).
18.
Kokoris SI, Gavriilaki E, Miari A et al. Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features, pathophysiology and treatment. Hematology 23(8), 558–566 (2018).
19.
Sahin F, Akay OM, Ayer M et al. PESG PNH diagnosis, follow-up and treatment guidelines. Am. J Blood Res. 6(2), 19–27 (2016).
20.
Phillippe HM. Overview of venous thromboembolism. Am. J. Manag. Care 23(Suppl. 20), S376–S382 (2017).
21.
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. 99(7), 1505–1514 (2020).
22.
Devalet B, Mullier F, Chatelain B, Dogné JM, Chatelain C. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. Eur. J. Hematol. 95(3), 190–198 (2015).
23.
Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: current treatments and unmet needs. J. Manag. Care Spec. Pharm. 26(Suppl. 12-b), S14–S20 (2020).
24.
Levy AR, Dysart L, Patel Y et al. Comparison of lost productivity due to eculizumab and ravulizumab treatments for paroxysmal nocturnal hemoglobinuria in France, Germany, Italy, Russia, Spain, the United Kingdom, and the United States. Blood 134, 4803 (2019).
25.
Aamds. PNH—paroxysmal nocturnal hemoglobinuria. (2020).
26.
Young NS, Meyers G, Schrezenmeier H, Hillmen P, Hill A. The management of paroxysmal nocturnal hemoglobinuria: recent advances in diagnosis and treatment and new hope for patients. Semin. Hematol. 46(Suppl. 1), S1–S16 (2009).
27.
Platzbecker U, Hofbauer LC, Ehninger G, Holig K. The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes. Leuk. Res. 36(5), 525–536 (2012).
28.
Santarone S, Bacigalupo A, Risitano AM et al. Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). ematologica 95(6), 983–988 (2010).
29.
Ravulizumab for treating paroxysmal nocturnal hemoglobinuria. Technology appraisal guidance [TA698] (15 November). www.nice.org.uk/guidance/ta698/chapter/3-Committee-discussion#treatment-pathway
30.
McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal hemoglobinuria. Drugs 71(17), 2327–2345 (2011).
31.
Alexion. Solirus (eculizumab) [package insert]. US Food and Drug Administration website (2021). www.accessdata.fda.gov/drugsatfda_docs/label/2017/125166s422lbl.pdf
32.
Kelly RJ, Hill A, Arnold LM et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117(25), 6786–6792 (2011).
33.
Stern RM, Connell NT. Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria. Ther. Adv. Hematol. 10, 2040620719874728 (2019).
34.
Ultomiris 300 mg/30 ml concentrate for solution for infusion. Summary of Product Characteristics (SmPC) (15 November). www.medicines.org.uk/emc/product/10457/smpc#gref
35.
Recommendation: Ravulizumab for treating paroxysmal nocturnal hemoglobinuria Technology appraisal guidance [TA698] (15 November). www.nice.org.uk/guidance/ta698/chapter/1-Recommendations
36.
Füreder W, Valent P. Switching from high-dose eculizumab to ravulizumab in paroxysmal nocturnal hemoglobinuria: a case report. HemaSphere 4(4), e455 (2020).
37.
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 15(9), e0237497 (2020).
38.
Gurnari C, Nautiyal I, Pagliuca S. Current opinions on the clinical utility of ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Ther. Clin. Risk Manag. 17, 1343–1351 (2021).
• Informed the present analysis regarding ravulizumab as the most relevant comparator for a cost–effectiveness analysis of pegcetacoplan.
39.
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 113(17), 4094–4100 (2009).
40.
Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren K-J. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J. Rare Dis. 16(1), 389 (2021).
41.
Hillmen P, Szer J, Weitz I et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 384(11), 1028–1037 (2021).
• Data from the pivotal trial of pegcetacoplan informed the clinical parameters of the Markov model.
42.
Empavali prescribing information (15 November). www.accessdata.fda.gov/drugsatfda_docs/label/2021/215014s000lbl.pdf
43.
Aspaveli 1 080 mg solution for infusion; Summary of Product Characteristics (SmPC) (2022). www.ema.europa.eu/en/documents/product-information/aspaveli-epar-product-information_en.pdf
44.
ASPAVELI 1 080 mg solution for infusion (29 March). https://mhraproducts4853.blob.core.windows.net/docs/f5c79734c69d0ee30732d383edff42be050e9c90
45.
Röth A, Hoechsmann B, Griffin M et al. Effect of pegcetacoplan on quality of life in patients with paroxysmal nocturnal hemoglobinuria from the pegasus Phase 3 trial comparing pegcetacoplan to eculizumab. Blood 136(Suppl. 1), 10–12 (2020).
46.
Godman B, Bucsics A, Vella Bonanno P et al. Barriers for access to new medicines: searching for the balance between rising costs and limited budgets. Front. in Public Health 6(328), (2018).
47.
Blonda A, Denier Y, Huys I, Simoens S. How to value orphan drugs? A review of European value assessment frameworks. Front. Pharmacol. 12 (2021).
48.
Methodological choices for the economic evaluation at HAS (10 September). www.has-sante.fr/jcms/r_1499251/fr/choix-methodologiques-pour-l-evaluation-economique-a-la-has
49.
The guidelines manual: process and methods [PMG6] (29 September). www.nice.org.uk/process/pmg6/chapter/assessing-cost-effectiveness
50.
Berdud M, Drummond M, Towse A. Establishing a reasonable price for an orphan drug. Cost Eff. Resour. Alloc. 18(1), 31 (2020).
51.
Sobi. Expert survey for collecting data Inputs for the cost–effectiveness model for pegcetacoplan in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in the US and UK. Data on file.
52.
Sobi. Pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH): United Kingdom (UK) health technology assessment virtual advisory board. Data on file. Advisory Board presented at; 2021 Apr 15; Virtual.
53.
Kulasekararaj AG, Hill A, Rottinghaus ST et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood 133(6), 540–549 (2019).
• Data were used to match average aggregate baseline characteristics reported in the ALXN1210-PNH-302 (Study 302) trial for patients receiving ravulizumab with the PEGASUS trial population.
54.
Bhak RH, Mody-Patel N, Baver SB et al. Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison. Curr. Med. Res. Opin. 37(11), 1913–1923 (2021).
• Data anchored the comparisons of clinical outcomes for pegcetacoplan and ravulizumab.
55.
Wook JL, de Fontbrune FS, Pessoa V et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood 133(6), 530–539 (2019).
56.
Advice: ravulizumab (Ultomiris®) for PNH (15 November). www.scottishmedicines.org.uk/media/5756/ravulizumab-ultomiris-final-jan-2021-for-website.pdf
57.
Sobi. Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: United Kingdom health technology assessment virtual advisory board. Data on file. Advisory Board; 2021 Apr 15; Virtual.
58.
Lee JW, Sicre De Fontbrune F, Wong Lee Lee L et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood 133(6), 530–539 (2019).
59.
Mapping of EQ-5D (24 September). http://nicedsu.org.uk/methods-development/mapping-of-eq-5d/
60.
Longworth L, Yang Y, Young T et al. Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: a systematic review, statistical modelling and survey. Health Technol. Assess 18(9), 1–224 (2014).
• This algorithm was used to validate the mapping approach for the EQ-5D data developed for the present analysis.
61.
Position statement on use of the EQ-5D-5L value set for England (29 September). www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/technology-appraisal-guidance/eq-5d-5l
62.
Longworth L, Rowen D. Mapping to obtain EQ-5D utility values for use in NICE health technology assessments. Value Health 16(1), 202–210 (2013).
63.
Mckenzie L, Van Der Pol M. Mapping the EORTC QLQ C-30 onto the EQ-5D instrument: the potential to estimate QALYs without generic preference data. Value Health 12(1), 167–171 (2009).
64.
Stoner KL, Harder H, Fallowfield LJ, Jenkins VA. Intravenous versus subcutaneous drug administration. Which do patients prefer? A systematic review. Patient (2014).
• This review indicated that patients have reported a preference for subcutaneous over IV delivery in other disease settings, a key treatment benefit of pegcetacoplan.
65.
Advice: eculizumab (Soliris) for PNH (15 November). www.scottishmedicines.org.uk/medicines-advice/eculizumab-soliris-for-pnh-fullsubmission-113016/
66.
Cherry MG, Greenhalgh J, Osipenko L et al. The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation. Health Technol Assess 16(43), 1–129 (2012).
67.
Ultomiris (ravulizumab) EPAR (15 November). www.ema.europa.eu/en/medicines/human/EPAR/ultomiris
68.
Unit Costs of Health and Social Care (15 November). www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2019
69.
NHS Reference Costs (15 November). www.england.nhs.uk/publication/2019-20-national-cost-collection-data-publication/
70.
Routine preoperative tests for elective surgery (15 November). www.nice.org.uk/guidance/ng45
71.
Eculizumab (15 November). https://bnf.nice.org.uk/medicinal-forms/eculizumab.html
72.
NICE. 5 The reference case | Guide to the methods of technology appraisal 2013 | Guidance | NICE [Internet]. NICE. NICE; 2013 [cited 2021 May 12] www.nice.org.uk/process/pmg9/resources/guide-to-the-methods-of-technology-appraisal-2013-pdf-2007975843781
73.
Charlton V. NICE and Fair? Health Technology Assessment Policy Under the UK's National Institute for Health and Care Excellence, 1999–2018. Health Care Anal. 28(3), 193–227 (2020).
74.
Debureaux P CF, Silva B, Barone F, De Fontbrune F et al. Hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: application of a novel classification to identify unmet clinical needs and future clinical goals. Blood 384, 3517 (2021).
75.
Levy AR, Tomazos I, Patel Y, Donato BMK, Briggs A. PSY15 Comparison of lost productivity due to eculizumab and ravulizumab treatments for paroxysmal nocturnal hemoglobinuria in the United States. Value in Health 22, S377 (2019).
76.
Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs 32(5), 425–440 (2018).
77.
Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N. Home-based subcutaneous immunoglobulin versus hospital-based intravenous immunoglobulin in treatment of primary antibody deficiencies: systematic review and meta analysis. J. Clin. Immunol. 32(6), 1180–1192 (2012).
78.
Weitz I, Meyers G, Lamy T et al. Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal hemoglobinuria. Intern Med. J. 43(3), 298–307 (2013).
79.
hemoglobin concentrations for the diagnosis of anemia and assessment of severity (18 January). www.who.int/vmnis/indicators/hemoglobin.pdf
80.
Hillmen P, Young NS, Schubert J et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 355(12), 1233–1243 (2006).
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Received: 14 April 2022
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Published online: 7 July 2022
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The cost–effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting. (2022) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2022-0076
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