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

  • Am J Respir Crit Care Med. 2022 Jun 1;205(11):1290-1299. doi: 10.1164/rccm.202108-1859OC.
Gerard J Criner  1 ,  Frederick M Lang  2  3  4 ,  Robert L Gottlieb  5  6  7 ,  Kusum S Mathews  8 ,  Tisha S Wang  9 ,  Todd W Rice  10 ,  Deepu Madduri  8 ,  Shashi Bellam  11 ,  Robert Jeanfreau  12 ,  Amy H Case  13 ,  Marilyn K Glassberg  14 ,  George Marshall Lyon  15 ,  Kareem Ahmad  16 ,  Robert Mendelson  17 ,  J Michael DiMaio  6 ,  MaryAnn P Tran  18 ,  Cedric W Spak  5  19 ,  Jamil A Abbasi  20 ,  Steven G Davis  21 ,  Shekhar Ghamande  22 ,  Steven Shen  2  3  23 ,  Lisa Sherman  2  3 ,  Simon Lowry  2  3
Affiliations
  • 1. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
  • 2. Roivant Sciences, New York, New York.
  • 3. Kinevant Sciences, a wholly-owned subsidiary of Roivant Sciences, New York, New York.
  • 4. Columbia University Vagelos College of Physicians and Surgeons, New York, New York.
  • 5. Baylor University Medical Center, Dallas, Texas.
  • 6. Baylor Scott & White The Heart Hospital-Plano, Plano, Texas.
  • 7. Baylor Scott & White Heart and Vascular Hospital, Dallas, Texas.
  • 8. Icahn School of Medicine at Mount Sinai, New York, New York.
  • 9. University of California Los Angeles David Geffen School of Medicine, Los Angeles, California.
  • 10. Vanderbilt University Medical Center, Nashville, Tennessee.
  • 11. NorthShore University HealthSystem, Evanston, Illinois.
  • 12. East Jefferson General Hospital, Metaire, Lousiana.
  • 13. Piedmont Healthcare, Atlanta, Georgia.
  • 14. University of Arizona College of Medicine/Banner University Medical Center, Phoenix, Arizona.
  • 15. Emory University School of Medicine, Atlanta, Georgia.
  • 16. Inova Fairfax Hospital, Falls Church, Virginia.
  • 17. Jamaica Hospital Medical Center, Jamaica, New York.
  • 18. Baylor Scott & White Medical Center-Round Rock, Round Rock, Texas.
  • 19. Texas Centers for Infectious Disease Associates, Dallas, Texas.
  • 20. Baylor Scott & White All Saints Medical Center, Fort Worth, Texas.
  • 21. Baylor Scott & White Medical Center-Irving, Irving, Texas.
  • 22. Baylor Scott & White Medical Center-Temple, Temple, Texas; and.
  • 23. Sumitovant Biopharma, New York, New York.
PMID: 35290169 DOI: 10.1164/rccm.202108-1859OC
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 [-6 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. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Keywords
COVID-19; GM-CSF; SARS-CoV-2; acute respiratory distress syndrome; gimsilumab.
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