LENZILUMAB OUTCOMES ACCORDING TO RACE OF COVID-19 PARTICIPANTS IN THE LIVE-AIR PHASE 3 TRIAL (preprint)

ABSTRACT

RATIONALE The hyperinflammatory immune response of COVID-19, in part orchestrated by granulocyte-macrophage colony-stimulating factor (GM-CSF) can lead to respiratory failure and death with disparities in outcomes between racial subgroups. In the LIVE-AIR trial, the GM-CSF neutralizing antibody lenzilumab improved survival without mechanical ventilation (SWOV) in COVID-19. OBJECTIVE: An analysis of outcomes was performed to determine differences between Black/African American (B/AA) and White participants in LIVE-AIR. METHODS: LIVE-AIR was a phase 3, randomized, double-blind, placebo-controlled trial. Participants hospitalized with COVID-19 pneumonia were randomized 11 to receive lenzilumab (1800 mg total) or placebo in addition to standard of care, including remdesivir and/or corticosteroids. MEASUREMENTS AND MAIN RESULTS: Lenzilumab, compared to placebo, numerically improved the likelihood of SWOV (primary endpoint) in B/AA (n=71; 86.8% vs 70.9%; HR, 2.68; 95% confidence interval [CI], 0.88-8.11; p=0.0814) and White (n=343; 85.1% vs 80.8%; HR, 1.41; 95%CI, 0.85-2.35, p=0.182) participants. A statistically significant improvement in SWOV was observed in B/AA (HR 8.9; 95%CI 1.08, 73.09; p=0.0418) and White (HR 2.32; 95%CI 1.17, 4.61; p=0.0166) participants with baseline CRP<150 mg/L. Lenzilumab numerically, but not statistically, improved secondary endpoints of IMV, ECMO or mortality; ventilator-free days; ICU days and time to recovery in either race while ventilator-free days, ICU days, and time to recovery were statistically improved in B/AA participants with baseline CRP<150 mg/L. Lenzilumab was well tolerated without differences in serious adverse events regardless of race. CONCLUSION: Lenzilumab significantly improved SWOV and some key secondary outcomes in B/AA COVID-19 participants with baseline CRP<150 mg/L. NCT04351152