Table 5e. 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The information in this table may include data from preprints or articles that have not been peer reviewed.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 5e. 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 Brazil^1,2
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.
Key: ANC = absolute neutrophil count; BMI = body mass index; CRP = C-reactive protein; ECMO = extracorporeal membrane oxygenation; GM-CSF = granulocyte-macrophage colony-stimulating factor; HFNC = high-flow nasal cannula; ICU = intensive care unit; IL = interleukin; IV = intravenous; mAb = monoclonal antibody; MV = mechanical ventilation; NIV = noninvasive ventilation; RCT = randomized controlled trial; RDV = remdesivir; SOC = standard of care; SOFA = sequential organ failure assessment; SpO₂ = oxygen saturation; ULN = upper limit of normal

References

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.
Temesgen Z, Kelley CF, Cerasoli F, et al. C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial. Thorax. 2022. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35793833.
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.
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.