Anti-Granulocyte–Macrophage Colony–Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia A Randomized, Double-Blind, Placebo-controlled Trial

Gerard J. Criner, Frederick M. Lang, Robert L. Gottlieb, Kusum S. Mathews, Tisha S. Wang, Todd W. Rice, Deepu Madduri, Shashi Bellam, Robert Jeanfreau, Amy H. Case, Marilyn K. Glassberg, George Marshall Lyon, Kareem Ahmad, Robert Mendelson, J. Michael DiMaio, Mary Ann P. Tran, Cedric W. Spak, Jamil A. Abbasi, Steven G. Davis, Shekhar GhamandeSteven Shen, Lisa Sherman, Simon Lowry

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Rationale: GM-CSF (granulocyte–macrophage colony–stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti–GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [26 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti–GM-CSF therapy for COVID-19 remains unclear.

Original languageEnglish (US)
Pages (from-to)1290-1299
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume205
Issue number11
DOIs
StatePublished - Jun 1 2022
Externally publishedYes

Keywords

  • COVID-19
  • GM-CSF
  • SARS-CoV-2
  • acute respiratory distress syndrome
  • gimsilumab

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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