title: A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.
abstract: BACKGROUND
  Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller.
  
  
  METHODS
  Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide).
  
  
  RESULTS
  Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment.
  
  
  CONCLUSIONS
  Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01582503.
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA. harris.jeffrey@gene.com.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Romeo
authors.initials: R
authors.lastname: Maciuca
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Bradley
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cabanski
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Heleen
authors.initials: H
authors.lastname: Scheerens
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Lim
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Kishnani
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: X Charlene
authors.initials: XC
authors.lastname: Liao
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Samineni
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
authors.forename: Colette
authors.initials: C
authors.lastname: Cochran
authors.affiliation: Alabama Allergy & Asthma Center, Birmingham, AL, USA.
authors.forename: Weily
authors.initials: W
authors.lastname: Soong
authors.affiliation: Allergy and Asthma Research Center PA, San Antonio, TX, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Diaz
authors.affiliation: Allergy Partners of New Jersey, Teaneck, NJ, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Perin
authors.affiliation: Clínica Ricardo Palma, Lima, Peru.
authors.forename: Miguel
authors.initials: M
authors.lastname: Tsukayama
authors.affiliation: Trakia University, Stara Zagora, Bulgaria.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dimov
authors.affiliation: Transylvania University, Faculty of Medicine, Brasov, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Agache
authors.affiliation: Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kelsen
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; C026408:anti-IgE antibodies
keywords: Allergic asthma; Biomarkers; COSTA; Exacerbations; FEV1; IgE; M1 prime; Quilizumab