In hospitalized patients with COVID-19 pneumonia, treatment with the monoclonal antibody lenzilumab has been shown to significantly improve survival without the need for mechanical ventilation. The phase 3, randomized, double-blind, placebo-controlled LIVE-AIR trial (ClinicalTrials.gov identifier: NCT04351152) was conducted among patients in the United States and in Brazil. Results of the analysis were published in The Lancet Respiratory Medicine.
The investigators sought to evaluate the efficacy and safety of lenzilumab for treating COVID-19 beyond the available treatments. The study enrolled patients hospitalized with COVID-19 pneumonia from 29 sites in the US and Brazil between May 2020 and January 2021, with 85% of the participants from US sites. Patients eligible for enrollment in LIVE-AIR needed to be at least 18 years of age, have virologically confirmed SARS-CoV-2 infection, and have pneumonia diagnosed by a chest x-ray or computed tomography scan.
All of the participants were randomly assigned in a 1:1 ratio to receive lenzilumab or matched placebo, in addition to standard treatment, per the institutional guidelines at each of the sites. All patients were stratified at randomization by age (≤65 years and >65 years) and disease severity. After screening and baseline measurements, lenzilumab or matching placebo was administered by intravenous (IV) infusions beginning on day 0 within 12 hours of randomization, in addition to standard care. Overall, 3 doses of lenzilumab (600 mg each) or placebo were administered 8 hours apart via a 1-hour IV infusion per dose.
The primary study endpoint was survival without the need for invasive mechanical ventilation to day 28 in the modified intention-to-treat (mITT) population, which comprised all randomized patients who received at least 1 dose of the study drug. A total of 528 patients were screened, 520 of whom were randomly assigned and included in the ITT population. Of these patients, 479 (lenzilumab arm, n=236; placebo arm, n=243) were included in the mITT analysis for the primary outcome. Overall, 65% of the participants were male. The mean patient age was 61±14 years; the median C-reactive protein level was 79 mg/L. Steroids were administered to 94% of the patients and remdesivir was administered to 72% of the patients, with 69% of the participants receiving both therapies.
Survival without the need for invasive mechanical ventilation to day 28 was attained in 84% (198 of 236) of patients in the lenzilumab group (95% CI, 79-89) and 78% (190 of 243) of those in the placebo group (95% CI, 72 -83). The likelihood of survival was greater with lenzilumab than with placebo (hazard ratio, 1.54; 95% CI, 1.02-2.32; P =.040).
Overall, 27% (68 of 255) of patients in the lenzilumab arm and 33% (84 of 257) of those in the placebo arm experienced at least 1 adverse event (AE) that was grade 3 or higher in severity. The most commonly reported treatment-emergent AEs (TEAEs) of grade 3 or higher were associated with respiratory disorders (26%) and cardiac disorders (6%), with none of the TEAEs leading to death.
The researchers concluded that ”Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalized patients with COVID-19, with a safety profile similar to that of placebo.” However, researchers also noted that “the added value of lenzilumab beyond the other immunomodulators used to treat COVID-19 alongside steroids remains to be confirmed.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Temesgen Z, Burger CD, Baker J, et al; LIVE-AIR Study Group. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. Published online December 1, 2021. doi:10.1016/S2213-2600(21)00494-X