To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (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, sex, 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 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and 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 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab.
Conclusion
In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with 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).
Cited by (0)
Potential Competing Interests: Dr Kenderian is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between Mayo Clinic, University of Pennsylvania, and Novartis) and Mettaforge (through Mayo Clinic). Drs Sakemura and Kenderian are inventors on patents in the field of CAR immunotherapy that are licensed to Humanigen (through Mayo Clinic). Dr Kenderian receives research funding from Kite, Gilead, Juno, Celgene, Novartis, Humanigen, MorphoSys, Tolero, Sunesis, and Lentigen; and has participated in advisory boards with Kite, Juno, Novartis, and Humanigen. Dr Badley is a consultant for AbbVie; is on scientific advisory boards for Nference and Zentalis; and is founder and President of Splissen Therapeutics. The remaining authors report no potential competing interests.
