title: Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies.
abstract: BACKGROUND
  In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity.
  
  
  METHODS
  LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies.
  
  
  RESULTS
  The median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose-response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed.
  
  
  CONCLUSIONS
  These data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment.
  
  
  BACKGROUND
  The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.affiliation: Allergy Associates Research, Portland, Oregon, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Noonan
authors.affiliation: Asthma and Allergy Research Foundation, Los Angeles, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Corren
authors.affiliation: Clinical Research Center LLC, St. Louis, Missouri, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Korenblat
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Saloumeh K
authors.initials: SK
authors.lastname: Fischer
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Cheu
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Putnam
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Murray
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Heleen
authors.initials: H
authors.lastname: Scheerens
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Cecile T J
authors.initials: CT
authors.lastname: Holweg
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Romeo
authors.initials: R
authors.lastname: Maciuca
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gray
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Ramona
authors.initials: R
authors.lastname: Doyle
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: McClintock
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Olsson
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Matthews
authors.affiliation: Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Yen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D007279:Injections, Subcutaneous; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C561806:lebrikizumab
keywords: Asthma; Asthma Mechanisms; Cytokine Biology