C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial

• Type of Material: Article
• Authors: Zelalem Temesgen, Mayo Clinic, Rochester; F Kelley Colleen, Emory University; Frank Cerasoli, Rx Medical Dynamics, LLC, New York; Adrian Kilcoyne, Humanigen Inc, Burlingame; Dale Chappell, Humanigen Inc, Burlingame; Cameron Durrant, Humanigen Inc, Burlingame; Omar Ahmed, Humanigen Inc, Burlingame; Gabrielle Chappell, Humanigen Inc, Burlingame; Victoria Catterson, BioSymetrics, Inc, New York; Christopher Polk, Atrium Health, Charlotte; Andrew Badley, Mayo Clinic, Rochester; Vincent C Marconi, Emory University
• Language: English
• Date: 2022-07-05
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2023 BMJ Publishing Group Ltd & British Thoracic Society
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/thoraxjnl-2022-218744
• Title of Journal or Parent Work: THORAX
• Volume: 78
• Issue: 6
• Start Page: 606
• End Page: 616
• Grant/Funding Information: Humanigen, Inc. the sponsor of LIVE-AIR funded all aspects of the LIVE-AIR study, participated in data collection analysis, interpretation, writing of the manuscript and the decision to submit the manuscript for publication. Humanigen members OA, DC, GC and CD had access to the raw data.
• Keywords: ARDS; Life Sciences & Biomedicine; Respiratory System; GENE; MORTALITY; Cytokine Biology; Critical Care; Pneumonia; Respiratory Infection; Science & Technology; GM-CSF; COVID-19
• Research Categories: Health Sciences, Health Care Management; Health Sciences, Medicine and Surgery; Health Sciences, Public Health

Abstract

Objective COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. Design A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. Participants Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. Interventions Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. Main outcome measures The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. Results SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. Conclusion Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. Trial registration number NCT04351152; ClinicalTrials.gov