Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study

Aleena Banerji, Jonathan A Bernstein, Douglas T Johnston, William R Lumry, Markus Magerl, Marcus Maurer, Inmaculada Martinez-Saguer, Andrea Zanichelli, James Hao, Neil Inhaber, Ming Yu, Marc A Riedl, HELP OLE Investigators, J Hébert, B Ritchie, G Sussman, W H Yang, E Aygören-Pürsün, M Magerl, I Martinez-Saguer, P Staubach, M Cicardi, M Shennak, R H Zaragoza-Urdaz, S Kiani-Alikhan, J Anderson, A Banerji, A P Baptist, J A Bernstein, P J Busse, T Craig, M Davis-Lorton, S Gierer, R G Gower, D Harris, J Jacobs, D T Johnston, H H Li, R F Lockey, P Lugar, W R Lumry, M E Manning, D L McNeil, I Melamed, W R Otto, S M Rehman, M A Riedl, L B Schwartz, R Shapiro, E Sher, A M Smith, D Soteres, R Tachdjian, H J Wedner, M E Weinstein, H Zafra, Aleena Banerji, Jonathan A Bernstein, Douglas T Johnston, William R Lumry, Markus Magerl, Marcus Maurer, Inmaculada Martinez-Saguer, Andrea Zanichelli, James Hao, Neil Inhaber, Ming Yu, Marc A Riedl, HELP OLE Investigators, J Hébert, B Ritchie, G Sussman, W H Yang, E Aygören-Pürsün, M Magerl, I Martinez-Saguer, P Staubach, M Cicardi, M Shennak, R H Zaragoza-Urdaz, S Kiani-Alikhan, J Anderson, A Banerji, A P Baptist, J A Bernstein, P J Busse, T Craig, M Davis-Lorton, S Gierer, R G Gower, D Harris, J Jacobs, D T Johnston, H H Li, R F Lockey, P Lugar, W R Lumry, M E Manning, D L McNeil, I Melamed, W R Otto, S M Rehman, M A Riedl, L B Schwartz, R Shapiro, E Sher, A M Smith, D Soteres, R Tachdjian, H J Wedner, M E Weinstein, H Zafra

Abstract

Background: The aim was to evaluate long-term effectiveness and safety of lanadelumab in patients ≥12 y old with hereditary angioedema (HAE) 1/2 (NCT02741596).

Methods: Rollover patients completing the HELP Study and continuing into HELP OLE received one lanadelumab 300 mg dose until first attack (dose-and-wait period), then 300 mg q2wks (regular dosing stage). Nonrollovers (newly enrolled) received lanadelumab 300 mg q2wks from day 0. Baseline attack rate for rollovers: ≥1 attack/4 weeks (based on run-in period attack rate during HELP Study); for nonrollovers: historical attack rate ≥1 attack/12 weeks. The planned treatment period was 33 months.

Results: 212 patients participated (109 rollovers, 103 nonrollovers); 81.6% completed ≥30 months on study (mean [SD], 29.6 [8.2] months). Lanadelumab markedly reduced mean HAE attack rate (reduction vs baseline: 87.4% overall). Patients were attack free for a mean of 97.7% of days during treatment; 81.8% and 68.9% of patients were attack free for ≥6 and ≥12 months, respectively. Angioedema Quality-of-Life total and domain scores improved from day 0 to end of study. Treatment-emergent adverse events (TEAEs) (excluding HAE attacks) were reported by 97.2% of patients; most commonly injection site pain (47.2%) and viral upper respiratory tract infection (42.0%). Treatment-related TEAEs were reported by 54.7% of patients. Most injection site reactions resolved within 1 hour (70.2%) or 1 day (92.6%). Six (2.8%) patients discontinued due to TEAEs. No treatment-related serious TEAEs or deaths were reported. Eleven treatment-related TEAEs of special interest were reported by seven (3.3%) patients.

Conclusion: Lanadelumab demonstrated sustained efficacy and acceptable tolerability with long-term use in HAE patients.

Keywords: HAE; HAE attacks; HELP OLE; hereditary angioedema; lanadelumab; long-term prophylaxis.

Conflict of interest statement

A. Banerji has received institutional research/study support from BioCryst and Takeda and/or honoraria for consulting from BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Takeda. J.A. Bernstein has been or is currently a clinical investigator for BioCryst, CSL Behring, Ionis, KalVista, Pharming, and Takeda; a speaker for CSL Behring, Pharming, and Takeda; a consultant for BioCryst, CSL Behring, Fresenius Kabi, Ionis, KalVista, Pharming, and Takeda; and a member of the hereditary angioedema medical advisory board. D.T. Johnston has received consulting/speaker fees from CSL Behring, Pharming, and Takeda, and consulting fees from BioCryst and REGENXBIO. W.R. Lumry is a member of advisory boards for BioCryst, CSL Behring, and Takeda; has received research grants from BioCryst, CSL Behring, Ionis, and Takeda; has received consulting fees from BioCryst, CSL Behring, Fresenius Kabi, Pharming, and Takeda; payments for lectures from CSL Behring, Pharming, and Takeda; and is an advisory board member of the US Hereditary Angioedema Association. M. Magerl has received research grant support and/or speaker/consultancy fees from BioCryst, CSL Behring, KalVista, Pharming, and Takeda. M. Maurer has received research grant support and/or speaker/consultancy fees from Adverum, BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Takeda. I. Martinez‐Saguer has received research grant support and/or speaker/consultancy fees from BioCryst, CSL Behring, KalVista, Pharming, and Takeda. A. Zanichelli has received speaker/consultancy fees from BioCryst, CSL Behring, Pharming, and Takeda. J. Hao, N. Inhaber, and M. Yu are full‐time employees of and hold stock/stock options in Takeda. M.A. Riedl has received research grants from BioCryst, CSL Behring, Pharming, and Takeda; has received consulting fees from Adverum, Attune, BioCryst, CSL Behring, Ionis, KalVista, Pharming, and Takeda; payments for lectures from CSL Behring, Pharming, and Takeda; and is an advisory board member of the US Hereditary Angioedema Association.

© 2021 Takeda Development Center Americas, Inc. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Patient disposition. †The category “withdrawal by patient” also included patients who transitioned to the commercial product (n = 117); see Table S1. ‡The number of patients who completed the study (n = 173) includes patients who transitioned to the commercial product (n = 117), as well those who remained in the study for its entire duration (n = 56). AE, adverse event; q2wks, every 2 weeks; q4wks, every 4 weeks
FIGURE 2
FIGURE 2
HAE attack reduction (A), responder analysis (B), and percentage of patients with maximum attack‐free period ≥6 months or ≥12 months (C). (A) Values above bars are mean attack rates. Mean change from baseline and mean (minimum, maximum) percentage change from baseline are shown. Baseline data were not available for nonrollover patients’ HAE attacks requiring acute treatment or for their high‐morbidity attacks. n values represent the number of patients with attack rate data during the treatment period. Three rollover patients who discontinued the study during the dose‐and‐wait period were not included in the analyses. Analyses were performed based on reported HAE Attack Assessment and Reporting Procedures severity, as follows: Mild—Transient or mild discomfort; Moderate—Mild to moderate limitation in activity, some assistance needed; Severe—Marked limitation in activity, assistance required. High‐morbidity attacks were defined as any attack that had ≥1 of the following characteristics: severe, resulted in hospitalization (except hospitalization for observation 1 group as applicable, based on their percentage reduction. Patients who had an attack rate of zero at baseline were excluded from the analysis. HAE, hereditary angioedema; q2wks, every 2 weeks
FIGURE 3
FIGURE 3
Time to first HAE attack during the dose‐and‐wait period (rollover safety population). Open circles on the lines refer to censored patients—those who discontinued the study prior to having an attack. HAE, hereditary angioedema; q2wks, every 2 weeks; q4wks, every 4 weeks

References

    1. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema‐The 2017 revision and update. Allergy 2018;73(8):1575–1596
    1. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1‐INH deficiency. J Allergy Clin Immunol 2012;130(3):692–697
    1. Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol 2013;111(5):329–336
    1. Johnston DT. Diagnosis and management of hereditary angioedema. J Am Osteopath Assoc 2011;111(1):28–36
    1. Craig T, Busse P, Gower RG, et al. Long‐term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency. Ann Allergy Asthma Immunol 2018;121(6):673–679
    1. Longhurst H, Bygum A. Humanistic, societal, and pharmaco‐economic burden of angioedema. Clin Rev Allergy Immunol 2016;51(2):230–239
    1. 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 2020;124(6):600–607
    1. Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc 2000;75(4):349–354
    1. Peter JG. Hereditary angioedema – together we can. Curr Allergy Clin Immunol 2019;32(3):148–152
    1. Maurer M, Aygören‐Pürsün E, Banerji A, et al. Consensus on treatment goals in hereditary angioedema: a global Delphi initiative. J Allergy Clin Immunol 2021;25(21):S0091–6749. 10.1016/j.jaci.2021.05.016
    1. Kaplan AP, Joseph K. The bradykinin‐forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010;104(3):193–204
    1. Kenniston JA, Faucette RR, Martik D, et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem 2014;289(34):23596–23608
    1. TAKHZYRO™ (lanadelumab‐flyo) injection, for subcutaneous use [ s of prescribing information]. Dyax Corp.; 2018.
    1. TAKHZYRO 300 mg solution for injection [summary of product characteristics]. Shire Pharmaceuticals Ireland Limited; 2018.
    1. Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol 2019;15:72
    1. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract 2021;9(1):132–150. e133
    1. Banerji A, Riedl MA, Bernstein JA, et al. HELP Investigators. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks. JAMA 2018;320(20):2108–2121
    1. Riedl MA, Maurer M, Bernstein JA, et al. HELP Investigators. Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks. Allergy 2020;75(11):2879–2887
    1. Riedl MA, Bernstein JA, Craig T, et al. An open‐label study to evaluate the long‐term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy 2017;7:36
    1. Weller K, Groffik A, Magerl M, et al. Development and construct validation of the angioedema quality of life questionnaire. Allergy 2012;67(10):1289–1298
    1. Weller K, Magerl M, Peveling‐Oberhag A, et al. The Angioedema Quality of Life Questionnaire (AE‐QoL) ‐ assessment of sensitivity to change and minimal clinically important difference. Allergy 2016;71(8):1203–1209
    1. Lumry WR, Weller K, Magerl M, et al. HELP Study Investigators. Impact of lanadelumab on health‐related quality of life in patients with hereditary angioedema in the HELP study. Allergy 2020;76(4):1188–1198

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren