Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one-year extension study

Marcus Maurer, Ana Giménez-Arnau, Jonathan A Bernstein, Chia-Yu Chu, Inna Danilycheva, Michihiro Hide, Michael Makris, Martin Metz, Sinisa Savic, Karl Sitz, Weily Soong, Petra Staubach, Gordon Sussman, Avantika Barve, Alis Burciu, Eva Hua, Reinhold Janocha, Thomas Severin, Marcus Maurer, Ana Giménez-Arnau, Jonathan A Bernstein, Chia-Yu Chu, Inna Danilycheva, Michihiro Hide, Michael Makris, Martin Metz, Sinisa Savic, Karl Sitz, Weily Soong, Petra Staubach, Gordon Sussman, Avantika Barve, Alis Burciu, Eva Hua, Reinhold Janocha, Thomas Severin

Abstract

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy.

Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study.

Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks.

Results: Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks.

Conclusion: The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown.

Trial registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.

Keywords: IgE; chronic spontaneous urticaria; ligelizumab; omalizumab; urticaria.

© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

References

REFERENCES

    1. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. The 2017 revision and update. Allergy. 2018;73(7):1393-1414.
    1. Kolkhir P, Altrichter S, Munoz M, Hawro T, Maurer M. New treatments for chronic urticaria. Ann Allergy Asthma Immunol. 2020;124(1):2-12.
    1. Kaplan AP. Diagnosis, pathogenesis, and treatment of chronic spontaneous urticaria. Allergy Asthma Proc. 2018;39(3):184-190.
    1. Guillen-Aguinaga S, Jauregui Presa I, Aguinaga-Ontoso E, Guillen-Grima F, Ferrer M. Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. Br J Dermatol. 2016;175(6):1153-1165.
    1. Fricke J, Ávila G, Keller T, et al. Prevalence of chronic urticaria in children and adults across the globe: systematic review with meta-analysis. Allergy. 2020;75(2):423-432.
    1. Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy. 2011;66(3):317-330.
    1. Yosipovitch G, Ansari N, Goon A, Chan YH, Goh CL. Clinical characteristics of pruritus in chronic idiopathic urticaria. Br J Dermatol. 2002;147(1):32-36.
    1. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414.
    1. Metz M, Vadasz Z, Kocatürk E, Giménez-Arnau AM. Omalizumab updosing in chronic spontaneous urticaria: an overview of real-world evidence. Clin Rev Allergy Immunol. 2020;59(1):38-45.
    1. Silvares MR, Fortes MR, Miot HA. Quality of life in chronic urticaria: a survey at a public university outpatient clinic, Botucatu (Brazil). Rev Assoc Med Bras (1992). 2011;57(5):577-582.
    1. Hollis K, Proctor C, McBride D, et al. Comparison of Urticaria Activity Score Over 7 Days (UAS7) values obtained from once-daily and twice-daily versions: results from the ASSURE-CSU study. Am J Clin Dermatol. 2018;19(2):267-274.
    1. Sussman G, Abuzakouk M, Bérard F, et al. Angioedema in chronic spontaneous urticaria is underdiagnosed and has a substantial impact: analyses from ASSURE-CSU. Allergy. 2018;73(8):1724-1734.
    1. Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015;135(1):67-75.
    1. Apalla Z, Sidiropoulos T, Kampouropoulou E, et al. Real-life, long-term data on efficacy, safety, response and discontinuation patterns of omalizumab in a Greek population with chronic spontaneous urticaria. Eur J Dermatol. 2020;30(6):716-722.
    1. Maurer M, Rosén K, Hsieh H-J, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368(10):924-935.
    1. Casale TB, Bernstein JA, Maurer M, et al. Similar efficacy with omalizumab in chronic idiopathic/spontaneous urticaria despite different background therapy. J Allergy Clin Immunol Pract. 2015;3(5):743-750. e741.
    1. Curto-Barredo L, Spertino J, Figueras-Nart I, et al. Omalizumab updosing allows disease activity control in patients with refractory chronic spontaneous urticaria. Br J Dermatol. 2018;179(1):210-212.
    1. Toubi E, Kessel A, Avshovich N, et al. Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients. Allergy. 2004;59(8):869-873.
    1. Kozel MM, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol. 2001;45(3):387-391.
    1. Staubach P, Eckhardt-Henn A, Dechene M, et al. Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity. Br J Dermatol. 2006;154(2):294-298.
    1. Beltrani VS. An overview of chronic urticaria. Clin Rev Allergy Immunol. 2002;23(2):147-169.
    1. Gaig P, Olona M, Munoz Lejarazu D, et al. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214-220.
    1. Kolkhir P, Church MK, Weller K, Metz M, Schmetzer O, Maurer M. Autoimmune chronic spontaneous urticaria: what we know and what we do not know. J Allergy Clin Immunol. 2017;139(6):1772-1781. e1771.
    1. Deza G, March-Rodríguez A, Sánchez S, et al. Relevance of the basophil high-affinity IgE receptor in chronic urticaria: clinical experience from a tertiary care institution. J Allergy Clin Immunol Pract. 2019;7(5):1619-1626. e1611.
    1. Deza G, Bertolín-Colilla M, Sánchez S, et al. Basophil FcɛRI expression is linked to time to omalizumab response in chronic spontaneous urticaria. J Allergy Clin Immunol. 2018;141(6):2313-2316.e1.
    1. Maurer M, Giménez-Arnau AM, Sussman G, et al. Ligelizumab for chronic spontaneous urticaria. N Engl J Med. 2019;381(14):1321-1332.
    1. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414.
    1. Kolkhir P, Altrichter S, Munoz M, Hawro T, Maurer M. New treatments for chronic urticaria. Ann Allergy Asthma Immunol. 2020;124(1):2-12.
    1. Gasser P, Tarchevskaya SS, Guntern P, et al. The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab. Nat Commun. 2020;11(1):165.
    1. Jensen RK, Jabs F, Miehe M, et al. Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy. Allergy. 2020;75(8):1956-1965.

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