1. Academic Validation
  2. GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study

  • Mayo Clin Proc. 2020 Nov;95(11):2382-2394. doi: 10.1016/j.mayocp.2020.08.038.
Zelalem Temesgen 1 Mariam Assi 2 F N U Shweta 2 Paschalis Vergidis 2 Stacey A Rizza 2 Philippe R Bauer 3 Brian W Pickering 4 Raymund R Razonable 2 Claudia R Libertin 5 Charles D Burger 6 Robert Orenstein 7 Hugo E Vargas 8 Raj Palraj 2 Ala S Dababneh 2 Gabrielle Chappell 9 Dale Chappell 9 Omar Ahmed 9 Reona Sakemura 10 Cameron Durrant 9 Saad S Kenderian 11 Andrew D Badley 12
Affiliations

Affiliations

  • 1 Division of Infectious Diseases, Mayo Clinic, Rochester, MN. Electronic address: [email protected].
  • 2 Division of Infectious Diseases, Mayo Clinic, Rochester, MN.
  • 3 Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
  • 4 Department of Anesthesia and Critical Care Medicine, Mayo Clinic, Rochester, MN.
  • 5 Division of Infectious Diseases, Mayo Clinic, Jacksonville, FL.
  • 6 Division of Pulmonary Medicine, Mayo Clinic, Jacksonville, FL.
  • 7 Division of Infectious Diseases, Mayo Clinic, Scottsdale, AZ.
  • 8 Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.
  • 9 Humanigen, Inc, Burlingame, CA.
  • 10 T Cell Engineering, Mayo Clinic, Rochester, MN; Division of Hematology, Mayo Clinic, Rochester, MN.
  • 11 T Cell Engineering, Mayo Clinic, Rochester, MN; Division of Hematology, Mayo Clinic, Rochester, MN; Department of Immunology, Mayo Clinic, Rochester, MN; Department of Molecular Medicine, Mayo Clinic, Rochester, MN.
  • 12 Division of Infectious Diseases, Mayo Clinic, Rochester, MN; Department of Molecular Medicine, Mayo Clinic, Rochester, MN.
Abstract

Objective: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia.

Methods: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death.

Results: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab.

Conclusion: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).

Figures
Products
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    Product Name
    Description
    Target
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  • HY-P99207
    99.64%, CSF2 Monoclonal Antibody