Skip to main content
U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock () or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Table 4d. Granulocyte-Macrophage Colony-Stimulating Factor Inhibitors: Selected Clinical Data

Last Updated: March 24, 2022

The clinical trials described in this table do not represent all the trials that the Panel reviewed while developing the recommendations for GM-CSF inhibitors. The studies summarized below are those that have had the greatest impact on the Panel’s recommendations.

The information in this table may include data from preprints or articles that have not been peer reviewed. This section will be updated as new information becomes available. Please see ClinicalTrials.gov for more information on clinical trials that are evaluating GM-CSF inhibitors.

Table 4d. Granulocyte-Macrophage Colony-Stimulating Factor Inhibitors: Selected Clinical Data
Methods Results Limitations and Interpretation
LIVE-AIR: Double-Blind RCT of Lenzilumab in Hospitalized Patients With Severe COVID-19 Pneumonia in the United States and Brazil1,2

Key Inclusion Criteria:

  • Hospitalized with SARS-CoV-2 pneumonia
  • SpO2 ≤94% on room air or required low-flow supplemental oxygen, HFNC oxygen, or NIV

Key Exclusion Criteria:

  • MV or ECMO

  • Bacterial pneumonia, fungal or viral infection

  • 48-hour survival not expected

  • Use of IL-1 inhibitors, IL-6 inhibitors, kinase inhibitors, or mAbs within prior 8 weeks

Interventions:

  • 3 doses of lenzilumab 600 mg IV 8 hours apart (n = 236)
  • Placebo (n = 243)

Primary Endpoint:

  • Survival without MV through Day 28

Key Secondary Endpoints:

  • Mortality
  • Incidence of death or requiring MV or ECMO

Exploratory Endpoint:

  • Survival without MV, stratified by baseline CRP

Participant Characteristics:

  • Mean age 61 years; 65% men; 72% White

  • 55% BMI ≥30

  • At baseline: 41% received HFNC oxygen or NIV

  • 94% received corticosteroids; 72% received RDV; 69% received corticosteroids and RDV

  • Median CRP 79 mg/L

Primary Outcome:

  • Survival without MV through Day 28: 84% in lenzilumab arm vs. 78% in placebo arm (HR 1.54; 95% CI, 1.02–2.32; P = 0.040)

Key Secondary Outcomes:

  • Mortality: 10% in lenzilumab arm vs. 14% in placebo arm (HR 0.72; 95% CI, 0.42–1.23; P = 0.24)
  • Incidence of death or requiring MV or ECMO: 15% in lenzilumab arm vs. 21% in placebo arm (HR 0.67; 95% CI, 0.41–1.10; P = 0.11)

Exploratory Outcome:

  • Survival without MV for baseline CRP <150 mg/L: 90% in lenzilumab arm vs. 79% in placebo arm (HR 2.54; 95% CI, 1.46–4.41; P = 0.0009)

Key Limitations:

  • Not powered to detect a survival benefit

  • Access to supportive care differed across study sites

Interpretation:

  • Lenzilumab improved ventilator-free survival in participants with hypoxemia who were not receiving MV, with the greatest benefit among those with lower CRP levels.
MASH-COVID: Double-Blind RCT of Mavrilimumab in Hospitalized Patients With Severe COVID-19 Pneumonia and Systemic Hyperinflammation in the United States3

Key Inclusion Criteria:

  • Hospitalization with SARS-CoV-2 pneumonia

  • SpO2 <92% on room air or required supplemental oxygen

  • CRP >5 mg/dL

Key Exclusion Criteria:

  • MV

  • ANC <1,500/mm3

  • Uncontrolled bacterial infection

Interventions:

  • Mavrilimumab 6 mg/kg as single IV infusion (n = 21)

  • Placebo (n = 19)

Primary Endpoint:

  • Alive and off supplemental oxygen at Day 14

Key Secondary Endpoints:

  • Mortality at Day 28

  • Alive without respiratory failure at Day 28

Participant Characteristics:

  • Median age 57 years; 65% men; 40% African American
  • At baseline:
    • 50% required HFNC oxygen or NIV
    • 65% received corticosteroids
    • 75% received RDV

Primary Outcome:

  • Alive and off supplemental oxygen at Day 14: 57% in mavrilimumab arm vs. 47% in placebo arm (OR 1.48; 95% CI, 0.43–5.16; P = 0.76)

Key Secondary Outcomes:

  • Mortality at Day 28: 1 (5%) in mavrilimumab arm vs. 3 (16%) in placebo arm (HR 3.72; 95% CI, 0.39–35.79; P = 0.22)
  • Alive without respiratory failure at Day 28: 95% in mavrilimumab arm vs. 79% in placebo arm (OR 5.33; 95% CI, 0.54–52.7; P = 0.43)

Key Limitations:

  • Very small sample size 
  • Ended early due to slow enrollment

Interpretation:

  • Among participants with systemic hyperinflammation and severe COVID-19 pneumonia, there was no evidence that use of mavrilimumab improved supplemental oxygen–free survival by Day 14.
OSCAR: Double-Blind RCT of Otilimab in Patients With Severe COVID-19 Pneumonia in 17 Countries4

Key Inclusion Criteria:

  • Hospitalized with SARS-CoV-2 pneumonia
  • Required HFNC oxygen, NIV, or MV ≤48 hours before dosing
  • CRP or ferritin >ULN

Key Exclusion Criteria:

  • Death likely <48 hours
  • Multiple organ failure
  • SOFA score >10 if in ICU
  • ECMO
  • Dialysis
  • High-dose noradrenaline (>0.15 ug/kg/min) or equivalent
  • >1 vasopressor

Interventions:

  • Otilimab 90 mg IV as single infusion (n = 395)
  • Placebo (n = 398)

Primary Endpoint:

  • Alive and free of respiratory failure at Day 28

Key Secondary Endpoint:

  • All-cause mortality at Day 60

Participant Characteristics:

  • Mean age 59 years; 72% men; 66% White
  • At baseline: 
    • 77% received HFNC oxygen or NIV; 22% received MV
    • 83% received corticosteroids; 34% received RDV

Primary Outcome:

  • Alive and free of respiratory failure at Day 28: 71% in otilimab arm vs. 67% in placebo arm (model-adjusted difference 5.3%; 95% CI, -0.8 to 11.4; P = 0.09)

Key Secondary Outcome:

  • All-cause mortality at Day 60: 23% in otilimab arm vs. 24% in placebo arm (model-adjusted difference -2.4%; 95% CI, -8.0 to 3.3; P = 0.41)

Key Limitations:

  • Changes in SOC during study may have affected outcomes.

Interpretation:

  • For participants with severe COVID-19 pneumonia, use of otilimab did not significantly reduce the probability of respiratory failure or death.

References

  1. Temesgen Z, Burger CD, Baker J, et al. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a Phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2021. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34863332.
  2. Temesgen Z, Kelley CF, Cerasoli F, et al. Early lenzilumab treatment of COVID-19 patients using c-reactive protein as a biomarker improves efficacy: results from the Phase 3 ‘LIVE-AIR’ trial. medRxiv. 2022;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2021.12.30.21267140v1.
  3. Cremer PC, Abbate A, Hudock K, et al. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021;3(6):e410-e418. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33754144.
  4. Patel J, Beishuizen A, Ruiz X, et al. A randomized trial of otilimab in severe COVID-19 pneumonia (OSCAR). medRxiv. 2021;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2021.04.14.21255475v1.