NIAID’s ACTIV-5 ‘Big Bet’ Looks to Win in Phase 3 Trial Showing Lenzilumab Improves COVID-19 Survival

NIAID’s ACTIV-5 ‘Big Bet’ Looks to Win in Phase 3 Trial Showing Lenzilumab Improves COVID-19 Survival

An investigational drug evidences positive results as a recent report about lenzilumab reveals that those treated with this drug along with other treatments, such as corticosteroids and/or remdesivir have a 54% better chance of survival without the use of a ventilator, superior results when compared to corticosteroids or remdesivir. With over 500 patients enrolled in a recent Phase 3 clinical trial, the biotech company Humanigen, Inc. reports they will seek to submit an application for emergency use authorization (EUA).

TrialSite provides a brief breakdown of this updated situation.

What is lenzilumab?

According to its maker Humanigen, lenzilumab is a humanized monoclonal antibody that targets colony stimulating factor 2 (CSF2)/granulocyte-macrophage colony stimulating factor (GM-CSF). First there was preclinical data and then early-stage clinical data suggesting that GM-CSF is a crucial initiator in the systemic inflammatory pathway driving the serious and life-threatening chimeric antigen receptor T cell (CAR-T) associated with what can become the deadly cytokine release syndrome (CRS). GM-CSF is produced by CAR-T cells upon recognition of target cells, as they trigger myeloid cells, compelling them to produce monocyte chemoattractant protein 1 (MCP-1) and CCR2, its receptor.  

GM-CSF knockout CAR-T cells appeared to protect mice from CRS but IL-6 knockout mice receiving wild-type CAR-T cells lacked protection from CRS.  Scientists found that mice infused with GM-CSF knockout CAR-T cells exhibit far less serum levels involving MCP-1, IL-6, MIG and MIP-1 than those mice receiving wild-type CAR-T cells, evidencing the role of GM-CSF signaling early in the inflammatory cascade.

Researchers have found thus far that using lenzilumab in a patient-derived xenograft model noticeably reduced CRS and neurotoxicity in collaboration with Kite (Gilead) and is currently in recruitment

What is this drug selected by the NIH for its ACTIV-5 “Big Effect” trial?

Yes. The “Big Effect” trial (NCT04583969) was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). A platform study, it consisted of a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized patients diagnosed with COVID-19.

A proof-of-concept study the intent of the sponsors included the identification of promising treatments to enter a more definitive study.  This initial platform study involved up to 40 trial site locations around America.

What were the results?

As far as for lenzilumab the Phase 3 study led to the results that the hospitalized patients that received the investigational product along with other authorized or accepted treatments, such as corticosteroids and/or remdesivir had a 54% greater relative likelihood of survival without the need for ventilation as compared to patients receiving the placebo.

Was the trial participation diverse?

According to Cameron Durrant, MD, MBA Chief Executive Officer of Humanigen “the trial incorporated a diverse population with various comorbidities, most commonly a body mass index above 30, which is representative of a real-world, high-risk population.”

What comes next?

Now the company will submit an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) as soon as possible. Obviously, they will need to wrap up the study and publish the results.

What is Humanigen background?

Humanigen is a clinical stage biotech developing their immunology and immuno-oncology portfolio of monoclonal antibodies. They focus their efforts on the development of their lead candidate, lenzilumab, their proprietary Humaneered® anti-human granulocyte-macrophage colony-stimulating factor (GM-CSF) monoclonal antibody. They were founded back in 2000.

Did the company just go public?

Yes, the company just floated their stock in an IPO, selling 5 million shares of its common stock for $18.50 per share resulting in proceeds totaling $92.5 million. The current price is 19.21 (NASDAQ: HGEN).


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  1. Humanigen may add ivermectin to the mix as they have left themselves open to do so here: “lenzilumab reveals that those treated with this drug ALONG WITH OTHER TREATMENTS , such as corticosteroids and/or remdesivir” …perhaps this is ok ?
    With the vaccine producers and wannabe’s all shoving ivermectin under the carpet while they obtain billions of dollars this may be a new twist to get their (Humanigen’s) drug into acceptance.
    Or have I read that wrong ?