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Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies
  1. Nicola A Hanania1,
  2. Michael Noonan2,
  3. Jonathan Corren3,
  4. Phillip Korenblat4,
  5. Yanan Zheng5,
  6. Saloumeh K Fischer5,
  7. Melissa Cheu5,
  8. Wendy S Putnam5,
  9. Elaine Murray5,
  10. Heleen Scheerens5,
  11. Cecile TJ Holweg5,
  12. Romeo Maciuca5,
  13. Sarah Gray5,
  14. Ramona Doyle5,
  15. Dana McClintock5,
  16. Julie Olsson5,
  17. John G Matthews5,
  18. Karl Yen5
  1. 1Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA
  2. 2Allergy Associates Research, Portland, Oregon, USA
  3. 3Asthma and Allergy Research Foundation, Los Angeles, California, USA
  4. 4Clinical Research Center LLC, St. Louis, Missouri, USA
  5. 5Genentech Inc. (a Member of the Roche Group), South San Francisco, California, USA
  1. Correspondence to Dr Karl Yen, Genentech Inc, 1 DNA Drive, South San Francisco, CA 94080-4990, USA; yen.karl{at}gene.com

Abstract

Introduction 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.

Trial registration numbers The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov

  • Asthma
  • Cytokine Biology
  • Asthma Mechanisms

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