Lenzilumab reduces likelihood of survival without ventilation in COVID-19 patients

In hospitalized COVID-19 patients, treatment with the novel GM-CSF* neutralizing monoclonal antibody lenzilumab led to a significant improvement in survival without invasive mechanical ventilation (SWOV), findings from the phase III LIVE-AIR study suggest.

“[Our] primary endpoint was achieved. Treatment with lenzilumab was associated with a statistically significant improved incidence of SWOV compared with placebo,” said Dr Zelalem Temesgen from the Mayo Clinic, Rochester, Minnesota, US, who presented the findings at ID Week 2021.

More lenzilumab vs placebo recipients achieved SWOV (84 percent vs 78 percent; hazard ratio [HR], 1.54; p=0.04). There was early separation of the Kaplan-Meier curves, which was maintained throughout the 28 days, noted Temesgen. [ID Week 2021, abstract 40]

There were also significant reductions in the rate of progression to IMV** (11 percent vs 20 percent; HR, 0.52; p=0.0059) and in ventilator days (3.5 vs 5.4 days; p=0.09) with lenzilumab vs placebo.

Albeit nonsignificant, death rate was numerically lower with lenzilumab vs placebo (10 percent vs 14 percent; HR, 0.72; p=0.24), as was the incidence of the composite secondary endpoint of IMV, ECMO**, or death (15 percent vs 21 percent; HR, 0.67; p=0.11) and ICU days (5.4 vs 6.6 days; p=0.16).

A total of 520 hypoxic patients (mean age 60.5 years, 65 percent male) hospitalized for COVID-19 with a clinical ordinal score of 3–5*** were evaluated. Nearly 60 percent required low-flow O₂ supplementation, while the rest were on high-flow O₂ or NIPPV^#. Participants were randomized 1:1 to receive lenzilumab 600 mg IV Q8H or placebo.

 

Lenzilumab plus other treatments

Participants were also receiving other standard treatments for COVID-19. About three-quarters (72 percent) were on remdesivir, 94 percent were on corticosteroids, while 69 percent received both.

Compared with those on placebo, a greater benefit was seen among lenzilumab recipients on a background of both remdesivir and corticosteroids, as seen by the significant improvements in SWOV (84 percent vs 73 percent; HR, 1.92; p=0.0067) and reductions in incidences of IMV (12 percent vs 25 percent; HR, 0.39; p=0.0007), the composite of IMV, ECMO, and death (14 percent vs 24 percent; HR, 0.51; p=0.018), and ventilator days (3.7 vs 6.7 days; p=0.018). Lenzilumab also conferred numerical reductions in the incidences of death (11 percent vs 18 percent; HR, 0.64; p=0.13) and ICU stay (5.7 vs 7.5 days; p=0.23) vs placebo.

Among those on a background of remdesivir, the rate of SWOV was also significantly greater with lenzilumab vs placebo (84 percent vs 74 percent; HR, 1.91; p=0.0073).

The lenzilumab treatment effect was consistent across most risk factors^##, except for those who were not receiving remdesivir and among patients treated in Brazil, noted Temesgen.

 

Safety

Lenzilumab was well-tolerated, with grade ≥3 adverse event (AE) rates similar to placebo (27 percent vs 33 percent). “Importantly, there were no reported SUSARs^###,” underscored Temesgen. There were also no serious AEs attributed to lenzilumab including infusion-related reactions, no cases of pulmonary alveolar proteinosis nor differences in laboratory, haematology, creatinine, or liver function parameters vs placebo.

The safety findings align with other studies evaluating lenzilumab in different therapeutic areas wherein lenzilumab exhibited an excellent safety profile, noted Temesgen.

 

GM-CSF neutralization a potential treatment pathway

GM-CSF is well-understood to be a key mediator of inflammation and tissue injury that triggers the immune-mediated cytokine storm, contributing to the pathology of COVID-19 including respiratory failure and death, Temesgen explained.

The findings underline the potential of GM-CSF neutralization to improve clinical outcomes in hospitalized COVID-19 patients not yet requiring MV. “[Their survival improved] without the need for MV. The benefit was in excess to standard background care, including remdesivir and corticosteroids,” said Temesgen.

A trial evaluating the efficacy and safety of lenzilumab plus remdesivir is underway. “[This shall] extend and confirm the observations noted in LIVE-AIR,” added Temesgen.