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

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.

Clinical and Economic Benefits of Lenzilumab Plus Standard of Care Compared with Standard of Care Alone for the Treatment of Hospitalized Patients with Coronavirus Disease 19 (COVID-19) from the Perspective of National Health Service England.

Purpose: To estimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of hospitalized COVID-19 patients from the National Health Service (NHS) England perspective. Methods: A cost calculator was developed to estimate the clinical benefits and costs of adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. The LIVE-AIR trial results informed the clinical inputs: failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included drug acquisition and administration for lenzilumab and remdesivir and hospital resource costs based on the level of care required. Clinical and economic benefits per weekly cohort of newly hospitalized patients were also estimated. Results: In all populations examined, specified clinical outcomes were improved with lenzilumab plus SOC over SOC treatment alone. In a base case population aged <85 years with C-reactive protein (CRP) <150 mg/L, with or without remdesivir, adding lenzilumab to SOC was estimated to result in per-patient cost savings of £1162. In a weekly cohort of 4754 newly hospitalized patients, addition of lenzilumab to SOC could result in 599 IMV uses avoided, 352 additional lives saved, and over £5.5 million in cost savings. Scenario results for per-patient cost savings included: 1) aged <85 years, CRP <150 mg/L, and receiving remdesivir (£3127); 2) Black patients with CRP <150 mg/L (£9977); and 3) Black patients from the full population (£2369). Conversely, in the full mITT population, results estimated additional cost of £4005 per patient. Conclusion: Findings support clinical benefits for SWOV, mortality, time to recovery, time in ICU, time on IMV, and ventilator use, and an economic benefit from the NHS England perspective when adding lenzilumab to SOC for hospitalized COVID-19 patients.

Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with COVID-19 in the United States from the hospital perspective.

AIMS: Estimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of patients hospitalized with COVID-19 pneumonia from the United States (US) hospital perspective. MATERIALS AND METHODS: A per-patient cost calculator was developed to report the clinical and economic benefits associated with adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. Clinical inputs were based on the LIVE-AIR trial, including failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included the anticipated list price of lenzilumab, drug administration, and hospital resource costs based on the level of care required. A scenario analysis examined projected one-year rehospitalization costs. RESULTS: In the base case and all scenarios, lenzilumab plus SOC improved all specified clinical outcomes relative to SOC alone. Lenzilumab plus SOC resulted in estimated cost savings of $3,190 per patient in a population aged <85 years with C-reactive protein (CRP) levels <150 mg/L and receiving remdesivir (base case). Per-patient cost savings were observed in the following scenarios: (1) aged <85 years with CRP <150 mg/L, with or without remdesivir ($1,858); (2) Black and African American patients with CRP <150 mg/L ($13,154); and (3) Black and African American patients from the full population, regardless of CRP level ($2,763). In the full modified intent-to-treat population, an additional cost of $4,952 per patient was estimated. When adding rehospitalization costs to the index hospitalization, a total per-patient cost savings of $5,154 was estimated. CONCLUSIONS: The results highlight the clinical benefits for SWOV, ventilator use, time to recovery, mortality, time in ICU, and time on IMV, in addition to an economic benefit from the US hospital perspective associated with adding lenzilumab to SOC for COVID-19 patients.

LENZILUMAB IN HOSPITALIZED BLACK/AFRICAN-AMERICAN COVID-19 PATIENTS: LIVE-AIR PHASE 3 STUDY RESULTS

The likelihood of SWOV was significantly improved by lenzilumab across races and ethnicities compared with placebo (HR: 1.54;95% CI: 1.02, 2.32;p=0.0403;N=479) and in patients with baseline CRP< 150 mg/L, < 85 years of age (HR 3.04;1.68, 5.51;p=0.0003;n=337). The hyperinflammatory cytokine storm accompanying SARS-CoV-2 infection is mediated by GM-CSF releasing downstream inflammatory chemokines, cytokines, and inflammatory markers including C-reactive protein (CRP), predictive of clinical worsening. B Background: b Black/African Americans (B/AA) are twice as likely as Whites to develop COVID-19, possibly due to disparities in healthcare access and genetics. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)