Lenzilumab for COVID-19 Improves Ventilator-Free Survival in Phase 3 Trial
Lenzilumab, a monoclonal antibody developed by Humanigen, appears safe and effective in treating coronavirus disease 2019 (COVID-19), according to a phase 3 clinical trial, which found a 54% increase in the likelihood of survival without ventilation in people receiving treatment.
The randomized, double-blind, placebo-controlled clinical trial known as “LIVE-AIR”, described in detail in a preprinted article in medRxiv, included 520 COVID-19 hospitalized patients with oxygen saturation equal to or less than 94% but not requiring invasive mechanical ventilation (IMV).
“Safe and effective therapies for treating hospitalized subjects with COVID-19 remain a significant unmet clinical need,” the study authors wrote. “In LIVE-AIR, early intervention with lenzilumab improved the relative likelihood of SWOV (ventilator-free survival) through day 28 by 54% in hospitalized, racially and ethnically diverse subjects with COVID-19, who had multiple comorbidities and were hypoxic but did not require mechanical ventilation at baseline. “
Study participants were divided into 2 groups, 261 receiving 3 intravenous infusions of 600 mg of lenzilumab 8 hours apart and 259 receiving placebo, with a follow-up period of 28 days. The study included a modified intention to treat group (mITT), which excluded patients in areas where supportive care was limited due to an increase in hospitalizations related to COVID-19.
Co-morbidities included obesity (55.1%), diabetes (53.4%), chronic renal failure (14.0%) and coronary artery disease (13.6%). Study participants were also treated with corticosteroids (93.7%), remdesivir (72.4%), or both (69.1%).
Ventilation-free survival was 54% improved among those who received lenzilumab compared to 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 in patients who received both corticosteroids and remdesivir (1.92; 1.20-3.07, nominal p = 0.0067) and an improvement 2.96 times in those under 85 years of age with a CRP less than 150 mg / L (2.96; 1.63–5.37, nominal p = 0.0003).
The study also showed improvements in secondary endpoints, including the incidence of IMV, ECMO, or death, especially in patients under 85 years of age with CRP less than 150 mg / L.
Adverse events were similar in 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).
“Results with lenzilumab on SWOV demonstrate that prevention of GM-CSF signaling at onset of CS is necessary to prevent progression of COVID-19 disease to IMV or death,” the authors wrote of the study. “This is further supported by an 88% improvement in SWOV in hospitalized subjects
Researchers explored 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. Combination therapy has been associated with a decrease in viral load and reduced progression of COVID-19 in 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 in patients requiring mechanical ventilation.