LENZILUMAB EFFICACY AND SAFETY IN NEWLY HOSPITALIZED COVID-19 SUBJECTS: RESULTS FROM THE LIVE-AIR PHASE 3 RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL

Abstract

BACKGROUND: Severe COVID19 pneumonia results from a hyperinflammatory immune response (cytokine storm, CS), characterized by GM CSF mediated activation and trafficking of myeloid cells, leading to elevation of downstream inflammatory chemokines (MCP1, IL8, IP10), cytokines (IL6, IL1), and other markers of systemic inflammation (CRP, D dimer, ferritin). CS leads to fever, hypotension, coagulopathy, respiratory failure, ARDS, and death. Lenzilumab is a novel Humaneered anti-human GM CSF monoclonal antibody that directly binds GM CSF and prevents signaling through its receptor. The LIVE AIR Phase 3 randomized, double blind, placebo controlled trial investigated the efficacy and safety of lenzilumab to assess the potential for lenzilumab to improve the likelihood of ventilator free survival (referred to herein as survival without ventilation, SWOV), beyond standard supportive care, in hospitalized subjects with severe COVID-19. METHODS: Subjects with COVID-19 (n=520), >18 years <94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Subjects were followed through Day 28 following treatment. RESULTS: Baseline demographics were comparable between the two treatment groups: male, 64.7%; mean age, 60.5 years; mean BMI, 32.5 kg/m2; mean CRP, 98.36 mg/L; CRP was <150 mg/L in 77.9% of subjects. The most common comorbidities were obesity (55.1%), diabetes (53.4%), chronic kidney disease (14.0%), and coronary artery disease (13.6%). Subjects received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the likelihood of SWOV by 54% in the mITT population (HR: 1.54; 95% CI: 1.02 to 2.31, p=0.041) and by 90% in the ITT population (HR: 1.90; 1.02 to 3.52, nominal p=0.043) compared to placebo. SWOV also relatively improved by 92% in subjects who received both corticosteroids and remdesivir (1.92; 1.20 to 3.07, nominal p=0.0067); by 2.96-fold in subjects with CRP<150 mg/L and age <85 years (2.96; 1.63 to 5.37, nominal p=0.0003); and by 88% in subjects hospitalized <2 days prior to randomization (1.88; 1.13 to 3.12, nominal p=0.015). Survival was improved by 2.17-fold in subjects with CRP<150 mg/L and age <85 years (2.17; 1.04 to 4.54, nominal p=0.040). CONCLUSION: Lenzilumab significantly improved SWOV in hospitalized, hypoxic subjects with COVID-19 pneumonia over and above treatment with remdesivir and/or corticosteroids. Subjects with CRP<150 mg/L and age <85 years demonstrated an improvement in survival and had the greatest benefit from lenzilumab. NCT04351152