First Clinical Use of Lenzilumab to Neutralize GM-CSF in Patients with Severe COVID-19 Pneumonia.

BACKGROUND

In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. With this rationale, we used lenzilumab, an anti-human GM-CSF monoclonal antibody, to treat patients with severe 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 IND application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. All patients receiving lenzilumab through May 1, 2020 were included in this report.

RESULTS

Twelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12 (92%), with a median time to discharge of 5 days. There was a significant improvement in oxygenation: The proportion of patients with SpO2/FiO2 < 315 at the end of observation was 8% vs. compared to 67% at baseline (p=0.00015). A significant improvement in mean CRP and IL-6 values on day 3 following lenzilumab administration was also observed (137.3 mg/L vs 51.2 mg/L, p = 0.040; 26.8 pg/mL vs 16.1 pg/mL, p = 0.035; respectively). Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab, and no mortality in this cohort of patients with severe COVID-19 pneumonia.

CONCLUSIONS

In high-risk COVID-19 patients with severe pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with improved clinical outcomes, oxygen requirement, and cytokine storm.