Ligelizumab treatment for severe asthma: learnings from the clinical development programme.
CD23
asthma
biologics
ligelizumab
omalizumab
Journal
Clinical & translational immunology
ISSN: 2050-0068
Titre abrégé: Clin Transl Immunology
Pays: Australia
ID NLM: 101638268
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
05
2020
revised:
30
11
2020
revised:
27
01
2021
accepted:
28
01
2021
entrez:
22
3
2021
pubmed:
23
3
2021
medline:
23
3
2021
Statut:
epublish
Résumé
Ligelizumab is a humanised IgG1 anti-IgE antibody that binds IgE with higher affinity than omalizumab. Ligelizumab had greater efficacy than omalizumab on inhaled and skin allergen provocation responses in mild allergic asthma. This multi-centre, randomised, double-blind study was designed to test ligelizumab in severe asthma patients not adequately controlled with high-dose inhaled corticoids plus long-acting β2-agonist. Patients received 16 weeks ligelizumab (240 mg q2w), omalizumab or placebo subcutaneously, and ACQ-7 was measured as primary outcome at Week 16. In addition, the study generated dose-ranging data of ligelizumab and safety data. A total of 471 patients, age 47.4 ± 13.36 years, were included in the study. Treatment with ligelizumab did not significantly improve asthma control (ACQ-7) and exacerbation rates compared to omalizumab and placebo. Therefore, primary and secondary objectives of the study were not met. The compound was well tolerated, and the safety profile showed no new safety findings. Pharmacokinetic data demonstrated faster clearance and lower serum concentrations of ligelizumab than historical omalizumab data, and exploratory Ligelizumab failed to demonstrate superiority over placebo or omalizumab. Although ligelizumab is more potent than omalizumab at inhibiting IgE binding to the high-affinity FcεRI, there is differential IgE blocking properties relative to FcεRI and FcεRII/CD23 between the two compounds. Therefore, the data suggest that different anti-IgE antibodies might be selectively efficacious for different IgE-mediated diseases.
Identifiants
pubmed: 33747510
doi: 10.1002/cti2.1255
pii: CTI21255
pmc: PMC7958305
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e1255Informations de copyright
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
Déclaration de conflit d'intérêts
JT has nothing to disclose. AG is an employee of Novartis. AP is an employee of Novartis Pharmaceuticals Corporation. HGZ is an employee of Novartis, during the conduct of the study. IB is an employee of Novartis Pharma AG. RW reports personal fees from Novartis Pharma AG, during the conduct of the study, and personal fees from Novartis Pharma AG, outside the submitted work. XJ is an employee of Novartis. CH has nothing to disclose. SZ reports grants and personal fees from bene‐Arzneimittel GmbH, grants and personal fees from Biotest GmbH, grants from Vifor Pharma Deutschland GmbH, grants from ALK Arzneimittel, personal fees from Novartis GmbH, personal fees from Böhringer Ingelheim, personal fees from Lofarma GmbH, personal fees from IMS HEALTH GmbH & Co. OHG, personal fees from GSK, personal fees from Stallergen, personal fees from Procter and Gamble, personal fees from Allergopharma GmbH, grants and personal fees from Allergy Therapeutics, personal fees from Engelhard Arzneimittel, personal fees from Sanofi‐Pasteur, personal fees from AstraZeneca, personal fees from EryDel, and personal fees from Bionorica GmbH, outside the submitted work.
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