Lenzilumab for COVID-19 Improves Survival Without Ventilation in Phase 3 Trial
Early treatment with lenzilumab improved the likelihood of survival without ventilation by 54% among patients hospitalized with COVID-19 who were hypoxic but not on invasive mechanical ventilation, a new study found.
Lenzilumab, a monoclonal antibody drug developed by Humanigen, appeared safe and effective for treating coronavirus disease 2019 (COVID-19), according to a phase 3 clinical trial, which found a 54% increase in likelihood of survival without ventilation among those receiving the treatment.
The randomized, double-blind, placebo-controlled clinical trial known as “LIVE-AIR,” detailed in a preprint article in medRxiv, included 520 hospitalized COVID-19 patients with oxygen saturation at or below 94% but not requiring invasive mechanical ventilation (IMV).
“Safe and effective therapeutics to treat hospitalized subjects with COVID-19 remains a significant unmet clinical need,” the study authors wrote. “In LIVE-AIR, early intervention with lenzilumab improved the relative likelihood of SWOV (survival without ventilation) through Day 28 by 54% in hospitalized, racially and ethnically diverse subjects with COVID-19, who had several comorbid conditions and were hypoxic but did not require mechanical ventilation at baseline.”
The study participants were divided into 2 groups, with 261 receiving 3 intravenous infusions of 600 mg lenzilumab 8 hours apart and 259 receiving a placebo, with a 28-day follow-up period. The study included a modified intent to treat group (mITT), which excluded patients in areas that experienced limitations to supportive care due to a surge in COVID-19 hospitalizations.
Comorbidities included obesity (55.1%), diabetes (53.4%), chronic kidney disease (14.0%) and coronary artery disease (13.6%). Participants in the study also were treated with corticosteroids (93.7%), remdesivir (72.4%) or both (69.1%).
Survival without ventilation was improved by 54% among those who received lenzilumab compared with the placebo group (HR: 1.54; 95% CI: 1.02-2.31, p=0.041). The study also showed a 92% relative improvement in SWOV among patients who received both corticosteroids and remdesivir (1.92; 1.20-3.07, nominal p=0.0067) and a 2.96-fold improvement among those under age 85 with CRP below 150 mg/L (2.96; 1.63–5.37, nominal p=0.0003).
The study also showed improvements in secondary endpoints, including incidence of IMV, ECMO or death, most notably among patients younger than 85 with CRP below 150 mg/L.
Adverse events were similar among those who received lenzilumab and those who received placebo.
Lenzilumab works by binding to GM-CSF and preventing a hyperinflammatory immune response, or cytokine storm (CS).
“The results with lenzilumab on SWOV demonstrate that impeding GM-CSF signaling early in CS is required to prevent COVID-19 disease progression to IMV or death,” the study authors wrote. “This is further supported by an 88% improvement in SWOV in subjects hospitalized < 2 days. The results herein with lenzilumab confirm results from prior clinical trials targeting GMCSF but are differentiated by patient selection, timing of intervention, and dosing strategy.”
Investigators have been exploring the use of monoclonal antibodies for the treatment and prevention of COVID-19. The first such drugs to receive Emergency Use Authorization from the Food and Drug Administration were Regeneron’s casirivimab and imdevimab. The combined therapy was associated with a decrease in viral load and a reduction in COVID-19 progression among patients with mild to moderate COVID-19.
Another recent study found that tocilizumab, a monoclonal antibody that targets interleukin 6 (IL-6), was associated with improved inflammatory markers and better respiratory and hemodynamic outcomes among patients requiring mechanical ventilation.