Lenzilumab Treatment Response in Hospitalized COVID-19 Patients Correlates with C-Reactive Protein Levels
- Multi-variate analysis of LIVE-AIR Phase 3 data demonstrates that elevated baseline C-Reactive Protein (“CRP”) is the most predictive feature for progression to invasive mechanical ventilation (“IMV”) or death and may be a useful biomarker to guide therapeutic intervention
- Patients with baseline CRP<150 mg/L who received lenzilumab had a more than 2.5-fold higher likelihood to survive without IMV than patients who received placebo (p<0.001)
- Findings suggest hospitalized COVID-19 patients who are early in the hyper-immune response, with lower baseline CRP levels (CRP<150 mg/l), achieve even greater clinical benefit from lenzilumab treatment
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an early upstream mediator and orchestrator of the hyperinflammatory immune response following SARS-CoV-2 infection and serves to activate and expand inflammatory myeloid cells. Increases in CRP are driven by elevations of myeloid cell derived downstream cytokines. Highly elevated levels of CRP (>150 mg/L) may indicate a stage of the hyperinflammatory immune response by which sufficient myeloid activation has already occurred, rendering GM-CSF neutralization less adequate to prevent further disease progression.
This analysis and publication provide evidence that a biomarker-driven approach utilizing baseline CRP levels to guide therapeutic intervention and patient selection may improve outcomes in patients hospitalized with COVID-19.
“We are encouraged by these results” said Dr.
About the LIVE-AIR, Phase 3 Study of Lenzilumab
This study was a randomized, double-blind, placebo-controlled, multi-center Phase 3 trial for the treatment and prevention of serious and potentially fatal outcomes in patients hospitalized with COVID-19 pneumonia. The primary objective was to assess whether lenzilumab, in addition to other treatments, which included dexamethasone (or other steroids) and/or remdesivir, could prevent or alleviate the immune-mediated ‘cytokine storm’ and improve survival without ventilation, or ‘SWOV’ (sometimes referred to as ‘ventilator-free survival’). SWOV is a composite endpoint of time to death and time to invasive mechanical ventilation (IMV) and SWOV is an important clinical endpoint that measures not only mortality, but the morbidity associated with mechanical ventilation. Approximately 94% of patients received dexamethasone (or other steroids), 72% received remdesivir, and 69% received both.
The LIVE-AIR study enrolled 520 patients in 29 sites in the US and
Lenzilumab is a proprietary Humaneered® first-in-class monoclonal antibody that has been proven to neutralize GM-CSF, a cytokine of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and other indications. Lenzilumab binds to and neutralizes GM-CSF, consequently improving outcomes for patients hospitalized with COVID-19.
In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study with Yescarta® in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results,
A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia (CMML) exhibiting RAS pathway mutations. This study builds on evidence from a Phase 1 study, conducted by
Lenzilumab is an investigational product and is not approved or authorized in any country.
All statements other than statements of historical facts contained in this press release are forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment, and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct, and you should be aware that actual events or results may differ materially from those contained in the forward- looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements, including, without limitation, statements regarding the ACTIV-5/BET-B study and the PREACH-M, SHIELD, RATinG and C-SMART studies, and other statements regarding our plans relating to lenzilumab and ifabotuzumab.
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