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
References
- 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
- 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
- Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol 2013;111(5):329–336
- Johnston DT. Diagnosis and management of hereditary angioedema. J Am Osteopath Assoc 2011;111(1):28–36
- 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
- Longhurst H, Bygum A. Humanistic, societal, and pharmaco‐economic burden of angioedema. Clin Rev Allergy Immunol 2016;51(2):230–239
- 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
- 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
- Peter JG. Hereditary angioedema – together we can. Curr Allergy Clin Immunol 2019;32(3):148–152
- 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
- Kaplan AP, Joseph K. The bradykinin‐forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010;104(3):193–204
- 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
- TAKHZYRO™ (lanadelumab‐flyo) injection, for subcutaneous use [ s of prescribing information]. Dyax Corp.; 2018.
- TAKHZYRO 300 mg solution for injection [summary of product characteristics]. Shire Pharmaceuticals Ireland Limited; 2018.
- Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol 2019;15:72
- 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
- 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
- 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
- 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
- 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
- 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
- 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