Lenzilumab improves survival without ventilation in patients hospitalized with COVID-19

Lenzilumab significantly improved survival without the need for invasive mechanical ventilation among patients hospitalized with COVID-19, according to results of the LIVE-AIR trial published in The Lancet Respiratory Medicine.

The safety profile of lenzilumab was similar to that of placebo, researchers reported.

“Lenzilumab is a novel anti-human granulocyte-macrophage colony-stimulating factor monoclonal antibody that directly binds granulocyte-macrophage colony-stimulating factor, with high specificity and affinity, and a slow off-rate to prevent signaling through its receptor,” Zelalem Temesgen, MD, infectious disease specialist in the division of infectious diseases at Mayo Clinic, Rochester, Minnesota, and colleagues wrote. “It has shown efficacy in clinical studies of various disease settings with no serious adverse events attributed to its administration.”

LIVE-AIR was a randomized, double-blind, placebo-controlled phase 3 trial that included 479 adults with COVID-19 pneumonia (mean age, 61 years; 65% men) who did not require invasive mechanical ventilation. Patients were enrolled from May 2020 to January 2021 at 29 sites in the U.S. and Brazil. Patients were randomly assigned to receive three doses of IV lenzilumab 600 mg (Humanigen; n = 236) or placebo (n = 243) administered 8 hours apart. In addition, all patients received standard supportive care including remdesivir (Veklury, Gilead Sciences) and corticosteroids; 94% of patients received steroids, 72% received remdesivir and 69% received both.

The primary outcome was survival at 28 days without invasive mechanical ventilation. The primary outcome was achieved in 84% of patients who received lenzilumab compared with 78% who received placebo (HR = 1.54; 95% CI, 1.02-2.32; P = .04).

The incidence of invasive mechanical ventilation, extracorporeal membrane oxygenation or death occurred in 15% of the lenzilumab group compared with 21% of the placebo group (OR = 0.67; 95% CI, 0.41-1.1; P = .11). Mean number of ventilator-free days was 8.8 in the lenzilumab group compared with 10.5 in the placebo group (P = .077). Mean ICU stay was 10 days for the lenzilumab group compared with 11 days for the placebo group (P = .16).

At baseline, median C-reactive protein (CRP) was 79 mg/L (77 mg/L in the lenzilumab group; 82 mg/L in the placebo group). Sensitivity analyses demonstrated that CRP levels below 79 mg/dL were associated with the greatest likelihood of survival without invasive mechanical ventilation.

“These exploratory findings might indicate the therapeutic potential of targeting a single upstream cytokine earlier in the disease process, guided by baseline CRP,” the researchers wrote.

At least one adverse event defined as grade 3 or higher in severity was reported in 27% of patients who received lenzilumab compared with 33% who received placebo. The most common treatment-emergent adverse events of grade 3 severity or higher were related to respiratory (25% and 28%, respectively) and cardiac (6% and 5%, respectively) disorders. No deaths related to adverse events occurred.

“Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalized patients with COVID-19 who were treated concurrently with other available therapies,” the researchers wrote. “However, the added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains to be confirmed.”

In September, Humanigen announced that the FDA declined its request for emergency use authorization (EUA) of lenzilumab in patients newly hospitalized with COVID-19. In its letter, the FDA said it was unable to conclude that the known and potential benefits of lenzilumab outweigh the known and potential risks of its use as a treatment for COVID-19, according to a company press release.

“We remain committed to bringing lenzilumab to patients hospitalized with COVID-19,” Cameron Durrant, MD, CEO of Humanigen said in the release. “We believe the ongoing ACTIV-5/BET-B trial, which has been advanced to enroll up to 500 patients, may provide additional safety and efficacy data sufficient to support our efforts to obtain an EUA to treat hospitalized COVID-19 patients.”

Reference:

FDA has declined Humanigen’s Emergency Use Authorization (EUA) Request for Lenzilumab in Hospitalized COVID-19 Patients. Published Sept. 9, 2021. Accessed Dec. 15, 2021.