The Lancet Respiratory Medicine publishes peer-reviewed paper and independent expert commentary on positive LIVE-AIR phase III lenzilumab results.- Humanigen, Inc.

The Lancet paper concludes “LIVE-AIR showed that lenzilumab treatment of hospitalised patients with COVID-19 can improve the likelihood of survival without the need for mechanical ventilation, with a safety profile similar to that of placebo.”

“This study of the treatment to prevent hyperinflammatory immune response that occurs in some patients infected with SARS-CoV-2 is important,” said Zelalem Temesgen, M.D., Mayo Clinic infectious disease researcher and principal investigator. “The need is great for more therapies for newly hospitalized patients prior to respiratory failure to reduce mortality or mechanical ventilation.”

The Lancet paper notes differences in CRP levels for LIVE-AIR patients compared to those of clinical trials for another immunomodulator to suggest these “findings might indicate the therapeutic potential of targeting a single upstream cytokine earlier in the disease process, guided by baseline CRP." ... The study contributes to the emerging body of evidence about how CRP concentrations relate to the pathogenesis of COVID-19 and to patient and treatment selection.” Related to the value of a CRP-guided approach to treatment of COVID-19 patients, the commentary noted “further study of a CRP-guided approach, possibly targeting patients with lower CRP concentrations, earlier in their disease course, ... could therefore be warranted.”

“One of the key components of the detrimental hyperinflammatory response in COVID-19 is granulocyte-macrophage colony-stimulating factor (GM-CSF). ... excessive GM-CSF production can contribute to the dysregulated immune response in severe COVID-19, in which, upstream of IL-1 and IL-6, activated T cells target neutrophils and macrophages. Agents that interfere with its actions have high plausibility for benefit, not just in COVID-19, but in other acute inflammatory conditions,” noted the commentary.

For hospitalized patients, “we now know that targeting the dysregulated host response is of greater value than targeting the virus.” The high level of uncertainty and concern surrounding the emergence of the Omicron variant highlights the ongoing need for variant-agnostic therapies.

See-"Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase III, randomised, placebo-controlled trial."-Prof Zelalem Temesgen, MD, Prof Charles D Burger, MD, Jason Baker, MD, Christopher Polk, MD, Prof Claudia R Libertin, MD, Colleen F Kelley, MD et al. Published: December 01, 2021DOI:https://doi.org/10.1016/S2213-2600(21)00494-X.The Lancet Respiratory Medicine.