Skip to main content
Search
Search
Advanced Search
Skip main navigation
Open access
Research Article
10 July 2025

Matching-adjusted indirect comparison between garadacimab and lanadelumab for the long-term prophylactic treatment of patients with hereditary angioedema

Authors: Sarah Walsh https://orcid.org/0000-0003-2988-6506, Anja Haltner https://orcid.org/0000-0002-9829-7791, Meaghan Bartlett https://orcid.org/0000-0003-4616-8776, John Sears, Yinglei Li, Maebh Kelly, Simona Gavata-Steiger, Chiara Nenci, Iris Jacobs, Ingo Pragst https://orcid.org/0000-0002-1259-5422, Neelanjana Ray, and Imtiaz A Samjoo https://orcid.org/0000-0003-1415-8055 [email protected]Author Info & Affiliations
Volume 14, Number 8
https://doi.org/10.57264/cer-2024-0237
PDFFormats

Abstract

Aim: This study aimed to estimate the relative efficacy between garadacimab 200 mg once monthly (200 QM) and two dosing regimens of lanadelumab (300 mg once every 2 weeks [300 Q2W] and 300 mg once every 4 weeks [300 Q4W]) in adolescent/adult patients with hereditary angioedema (HAE) using matching-adjusted indirect comparisons (MAICs), in the absence of head-to-head randomized controlled trials. Materials & methods: Individual patient data were available from the phase II (NCT03712228) and the phase III VANGUARD (NCT04656418) trials investigating garadacimab, and published summary-level data from the phase III HELP trial investigating lanadelumab (NCT02586805). The primary outcome was time-normalized number of HAE attacks. Secondary efficacy outcomes included time-normalized number of HAE attacks requiring on-demand treatment, time-normalized number of moderate and/or severe HAE attacks, and proportion of attack-free patients. Quality of life (QoL) was also assessed via change from baseline in AE-QoL total score. Results: Compared with lanadelumab 300 Q2W, garadacimab 200 QM statistically significantly reduced number of moderate and/or severe HAE attacks (rate ratio [RR]; 95% confidence interval: 0.25; 0.07, 0.84) and improved AE-QoL score (mean difference: -17.38; -33.67, -1.08). Compared with lanadelumab 300 Q4W, garadacimab 200 QM showed statistically significant improvements in all outcomes: HAE attacks (RR: 0.29; 0.13, 0.63), attacks requiring on-demand treatment (RR: 0.29; 0.13, 0.66), moderate and/or severe HAE attacks (RR: 0.15; 0.05, 0.49), proportion of attack-free patients (hazard ratio: 3.25; 1.45, 7.29), and AE-QoL score (mean difference: -21.29; -37.39, -5.18). Conclusion: These MAICs showed improved efficacy and QoL with garadacimab compared with lanadelumab across multiple endpoints. These findings demonstrate that garadacimab may provide improved therapeutic benefit compared with lanadelumab in the long-term prophylactic treatment of patients with HAE.

Supplementary Material

File (supplementary materials.docx)

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Bernstein J. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am. J. Manag. Care 24(Suppl. 14), S292–S298 (2018).
PubMed
Google Scholar
2.
Banerji A, Davis KH, Brown TM et al. Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Ann. Allergy Asthma Immunol. 124(6), 600–607 (2020).
PubMed
Google Scholar
3.
Mendivil J, Murphy R, de la Cruz M et al. Clinical characteristics and burden of illness in patients with hereditary angioedema: findings from a multinational patient survey. Orphanet J. Rare Dis. 16(1), 94 (2021).
PubMed
Google Scholar
4.
CSL312 (Garadacimab) in the prevention of hereditary angioedema attacks (NCT04656418). Updated 3 August 2022. Available from: https://ClinicalTrials.gov/show/NCT04656418
Google Scholar
5.
CSL Behring. Study Report: a multicenter, randomized, placebo-controlled, parallel-arm study to investigate the efficacy, pharmacokinetics, and safety of CSL312 in subjects with hereditary angioedema. (2022).
Google Scholar
6.
Craig TJ, Reshef A, Li HH et al. Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401(10382), 1079–1090 (2023).
Google Scholar
•• Presents baseline characteristics and primary and secondary outcome results (including efficacy and safety outcomes) from the pivotal Phase III VANGUARD trial investigating garadacimab.
7.
Cohn DM, Renné T. Targeting factor XIIa for therapeutic interference with hereditary angioedema. J. Intern. Med. 296(4), 311–326 (2024).
PubMed
Google Scholar
8.
CSL Behring. Long-term safety and efficacy of CSL 312 (garadacimab) in the prophylactic treatment of hereditary angioedema attacks. Updated 17 October 2022. Available from: https://clinicaltrials.gov/ct2/show/NCT04739059?term=garadacimab&draw=2&rank=2
Google Scholar
9.
EMA. Andembry garadacimab EMEA/H/C/006116 Authorisation Details. (2025).
Google Scholar
• Details the market authorization status of garadacimab by the EMA.
10.
Banerji A, Riedl MA, Bernstein JA et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA 320(20), 2108–2121 (2018).
PubMed
Google Scholar
•• Presents baseline characteristics and primary and secondary outcome results (including efficacy, safety and quality of life outcomes) from the Phase III HELP trial investigating lanadelumab.
11.
European Medicines Agency. Takhzyro (lanadelumab). Product information (2018). Available from: https://www.ema.europa.eu/en/documents/overview/takhzyro-epar-medicine-overview_en.pdf
Google Scholar
12.
Food and Drug Administration. TAKHZYRO® (lanadelumab-flyo) injection, for subcutaneous use 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761090s010lbl.pdf
Google Scholar
14.
TGA. Australian Public Assessment Report for Lanadelumab. Updated March 2020. Available from: https://www.tga.gov.au/sites/default/files/auspar-lanadelumab-200304.pdf
Google Scholar
15.
Phillippo D, Ades T, Dias S, Palmer S, Abrams KR, Welton N. NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE. (2016).
Google Scholar
•• Outlines recommendations for methods of conducting matching-adjusted indirect comparisons.
16.
Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J. Clin. Epidemiol. 50(6), 683–691 (1997).
PubMed
Google Scholar
17.
Phillippo DM, Ades AE, Dias S, Palmer S, Abrams KR, Welton NJ. Methods for population-adjusted indirect comparisons in health technology appraisal. Med. Decision Making 38(2), 200–211 (2018).
PubMed
Google Scholar
18.
Moher D, Shamseer L, Clarke M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 4(1), 1 (2015).
PubMed
Google Scholar
19.
Shamseer L, Moher D, Clarke M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350, g7647 (2015).
PubMed
Google Scholar
20.
York Uo. Systematic Reviews CRD's guidance for undertaking reviews in health care. (2008).
Google Scholar
21.
ClinicalTrials.gov. A study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). Updated 10 March 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03548207?term=NCT03548207&draw=2&rank=1
Google Scholar
22.
CSL Behring. 253590_CSL312_3001_Final_Tables_20220829. (2022).
Google Scholar
23.
Craig T, Magerl M, Levy DS et al. Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, Phase II trial. Lancet 399(10328), 945–955 (2022).
Google Scholar
24.
Signorovitch JE, Wu EQ, Yu AP et al. Comparative effectiveness without head-to-head trials. Pharmacoeconomics 28(10), 935–945 (2010).
PubMed
Google Scholar
25.
Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat. Med. 28(25), 3083–3107 (2009).
PubMed
Google Scholar
26.
Zeileis A. Object-oriented computation of sandwich estimators. J. Stat. Software 16(9), 1–16 (2006).
Google Scholar
27.
Zeileis A. Econometric computing with HC and HAC covariance matrix estimators. J. Stat. Software 11(10), 1–17 (2004).
Google Scholar
28.
CADTH. CADTH common drug review clinical review report for lanadelumab (Takhzyro). (2020).
Google Scholar
29.
Maurer M, Magerl M, Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2021 revision and update. Allergy 77(7), 1961–1990 (2022).
PubMed
Google Scholar
30.
Kulthanan K, Chularojanamontri L, Rujitharanawong C, Weerasubpong P, Maurer M, Weller K. Angioedema quality of life questionnaire (AE-QoL) – interpretability and sensitivity to change. Health Qual. Life Outcomes 17(1), 160 (2019).
PubMed
Google Scholar
31.
Watt M, Malmenäs M, Romanus D, Haeussler K. Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema. J. Comp. Eff. Res. 12(6), e220188 (2023).
PubMed
Google Scholar
• Presents efficacy results of an network meta-analyses (NMA) investigating lanadelumab versus berotralstat versus intravenous C1-esterase inhibitor.
32.
Mendivil JA-O, Malmenäs M, Haeussler K, Hunger M, Jain G, Devercelli G. Indirect comparison of lanadelumab and intravenous C1-INH using data from the HELP and CHANGE studies: bayesian and frequentist analyses. Drugs R D 21(1), 113–121 (2021).
PubMed
Google Scholar
• Presents efficacy results of an NMA investigating lanadelumab versus intravenous C1-esterase inhibitor.
33.
Wong JCY, Chiang V, Lam DLY et al. Long-term prophylaxis for hereditary angioedema: initial experiences with garadacimab and lanadelumab. J. Allergy Clin. Immunol. Glob. 2(4), 100166 (2023).
PubMed
Google Scholar
|