GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Control Study

Temesgen, Zelalem; Assi, Mariam; Shweta, F.N.U.; Vergidis, Paschalis; Rizza, Stacey A.; Bauer, Philippe R.; Pickering, Brian W.; Razonable, Raymund R.; Libertin, Claudia R.; Burger, Charles D.; Orenstein, Robert; Vargas, Hugo E.; Palraj, Raj; Dababneh, Ala S.; Chappell, Gabrielle; Chappell, Dale; Ahmed, Omar; Sakemura, Reona; Durrant, Cameron; Kenderian, Saad S.; Badley, Andrew D.

Objective To assess the efficacy and safety of lenzilumab in 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 investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, gender, and disease severity. Study dates were March 13, 2020 to June 18, 2020. All patients were followed through hospital discharge or death. Results Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 out of 12 (92%) lenzilumab treated patients and 22 out of 27 (81%) untreated patients. The time to clinical improvement was significantly shorter for lenzilumab-treated group compared to the untreated cohort: median 5 days vs. 11 days (P = .006). Similarly, the proportion of patients with acute respiratory distress syndrome (ARDS) (SpO2/FiO2 < 315) was significantly reduced over time when treated with lenzilumab compared to untreated (P < .001). Significant improvement in inflammatory markers (C-Reactive Protein, interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. Conclusions In high-risk COVID-19 patients with severe pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared to a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo controlled clinical trial to validate these findings is ongoing (NCT04351152).