The Cytokine Storm Company
Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), is a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’. Lenzilumab is a first-in class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF). Results from preclinical models indicate GM-CSF is an upstream regulator of many inflammatory cytokines and chemokines involved in the cytokine storm. Early in the COVID-19 pandemic, investigation showed high levels of GM-CSF secreting T cells were associated with disease severity and intensive care unit admission.
Humanigen’s Phase 3 LIVE-AIR study suggests early intervention with lenzilumab may prevent consequences of a full-blown cytokine storm in hospitalized patients with COVID-19. Humanigen is developing lenzilumab as a treatment for cytokine storm associated with COVID-19 and CD19-targeted CAR-T cell therapies and is also exploring the effectiveness of lenzilumab in other inflammatory conditions such as acute Graft versus Host Disease in patients undergoing allogeneic hematopoietic stem cell transplantation, eosinophilic asthma, and rheumatoid arthritis.
The Lancet Respiratory Medicine
Lenzilumab in hospitalised patients with COVID-19 pneumonia
(LIVE-AIR): a phase 3, randomised, placebo-controlled trial
Summary | Background: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes.
Early lenzilumab treatment of COVID-19 patients using c-reactive protein as a biomarker improves efficacy: results from the phase 3 ‘LIVE-AIR’ trial
Clinical and Economic Benefits of Lenzilumab from the Perspective of the National Health Service England
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
March 24, 2022,
Updated NIH COVID-19 Treatment Guidelines
Updated NIH COVID-19 Treatment Guidelines include updated results and interpretation from lenzilumab LIVE-AIR study now published in The Lancet Respiratory Medicine. The updated interpretation of LIVE-AIR concludes “Lenzilumab improved ventilator-free survival in participants with hypoxemia who were not receiving MV, with the greatest benefit among those with lower CRP levels”, based on the increased incidence of ventilator-free survival observed in patients with CRP <150 mg/L (90% vs 79%, HR 2.54; 95% CI, 1.46–4.41; P=0.0009). Currently, lenzilumab is not yet authorized or approved but is available via compassionate use in some countries (learn more). Guidelines state that while GM-CSF is believed to be a key driver of lung inflammation in COVID-19 pneumonia, operating upstream of other pro-inflammatory cytokines and chemokines, NIH interpretation of clinical data show that lenzilumab is the only GM-CSF inhibitor to demonstrate a benefit in the treatment of COVID-19. Lenzilumab may mitigate inflammation by inhibiting this signaling axis upstream of IL-6 and IL-1 and thus minimizing downstream production of numerous pro-inflammatory mediators involved in the pathogenesis of COVID-19.