title: Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses.
abstract: Omalizumab is an established anti-IgE therapy for the treatment of allergic diseases that prevents IgE from binding to its receptor. QGE031 is an investigational anti-IgE antibody that binds IgE with higher affinity than omalizumab.
  
  
  
  This study compared the effects of QGE031 with those of omalizumab on clinical efficacy, IgE levels, and FcεRI expression in a clinical model of allergic asthma.
  
  
  
  Thirty-seven patients with mild allergic asthma were randomized to subcutaneous omalizumab, placebo, or QGE031 at 24, 72, or 240 mg every 2 weeks for 10 weeks in a double-blind, parallel-group multicenter study. Inhaled allergen challenges and skin tests were conducted before dosing and at weeks 6, 12, and 18, and blood was collected until 24 weeks after the first dose.
  
  
  
  QGE031 elicited a concentration- and time-dependent change in the provocative concentration of allergen causing a 15% decrease in FEV1(allergen PC15) that was maximal and approximately 3-fold greater than that of omalizumab (P = .10) and 16-fold greater than that of placebo (P = .0001) at week 12 in the 240-mg cohort. Skin responses reached 85% suppression at week 12 in the 240-mg cohort and were maximal at week 18. The top doses of QGE031 consistently suppressed skin test responses among subjects but had a variable effect on allergen PC15(2-fold to 500-fold change). QGE031 was well tolerated.
  
  
  
  QGE031 has greater efficacy than omalizumab on inhaled and skin allergen responses in patients with mild allergic asthma. These data support the clinical development of QGE031 as a treatment of asthma.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Novartis Pharmaceuticals, East Hanover, and Novartis Pharma AG, Basel, Switzerland.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Departments of Medicine and Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.affiliation: Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
authors.affiliation: Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Davis
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Irvin
authors.initials: I
authors.lastname: Mayers
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: J Mark
authors.initials: JM
authors.lastname: FitzGerald
authors.affiliation: Karolinska Institutet, Department of Medicine, Karolinska University, Stockholm, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlen
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kieran J
authors.initials: KJ
authors.lastname: Killian
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carlsten
authors.affiliation: Karolinska Institutet, Department of Medicine, Karolinska University, Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lazarinis
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watson
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Milot
authors.affiliation: Departments of Medicine and Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Veronica
authors.initials: V
authors.lastname: Swystun
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Miranda
authors.initials: M
authors.lastname: Bowen
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Hui
authors.affiliation: Karolinska Institutet, Department of Medicine, Karolinska University, Stockholm, Sweden.
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Lantz
authors.affiliation: Novartis Pharmaceuticals, East Hanover, and Novartis Pharma AG, Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Meiser
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Maahs
authors.affiliation: Novartis Pharmaceuticals, East Hanover, and Novartis Pharma AG, Basel, Switzerland.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lowe
authors.affiliation: Novartis Pharmaceuticals, East Hanover, and Novartis Pharma AG, Basel, Switzerland.
authors.forename: Andrej
authors.initials: A
authors.lastname: Skerjanec
authors.affiliation: Novartis Pharmaceuticals, East Hanover, and Novartis Pharma AG, Basel, Switzerland. Electronic address: anton.drollmann@novartis.com.
authors.forename: Anton
authors.initials: A
authors.lastname: Drollmann
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D000069444:Omalizumab / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D000069444:Omalizumab; D007073:Immunoglobulin E; C000598891:ligelizumab
keywords: Asthma management; IgE; QGE031; allergy; biologics; immunology; ligelizumab; mAb