Humanigen Publishes Positive Phase 3 Trial Results for Variant-Agnostic COVID-19 Treatment Lenzilumab

Humanigen’s monoclonal antibody lenzilumab is safe and effective for treating hospitalized patients with COVID-19, the results of a phase 3 clinical trial confirmed.

The study, published in The Lancet Respiratory Medicine, included 520 patients hospitalized with COVID-19 but not requiring mechanical ventilation at 29 sites in the United States and Brazil from May 5, 2020, to Jan. 27, 2021. Participants were randomized in 2 groups to receive either 3 intravenous infusions of 600 mg of lenzilumab 8 hours apart or a placebo. The treatment was administered along with treatment such as corticosteroids and remdesivir.

“Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalized patients with COVID-19, with a safety profile similar to that of placebo,” the study authors, led by Zelalem Temesgen, MD, of the Mayo Clinic, wrote.

Lenzilumab is a variant-agnostic therapy that shows promise for treating hyperinflammatory response to SARS-CoV-2 infection by neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF), a key immune-mediated cytokine involved in the cytokine storm seen in COVID-19.

Known as LIVE-AIR, the study showed the primary outcome of survival without invasive mechanical ventilation to Day 28 was achieved in 198 patients (84%) in the lenzilumab group compared with 190 (78%)in the placebo group with a 54% greater likelihood of survival without ventilation among those in the treatment group (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040).

Adverse events of at least grade 3 in severity were reported among 68 (27%) patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group. None led to death.

“The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown,” the authors wrote.

The trial results were presented virtually in September during IDWeek 2021 and previously were detailed in a preprint article in medRxiv.

In September, the US Food and Drug Administration declined Humanigen’s request for Emergency Use Authorization of lenzilumab but invited the company to submit additional data as it becomes available. The company continues to work toward approval, with a second phase 2/3 clinical trial, the ACTIV-5/BET-B study, underway by the National Institutes of Health.

Humanigen CEO Cameron Durrant, MD, said the company plans to submit an amendment to its EUA application lenzilumab, known as LENZ, along with regulatory submissions in the European Union and the United Kingdom.

“The virus and the treatment landscape continue to evolve,” Durrant said in a statement in February. “We believe that COVID-19 will become a serious endemic disease and will continue to impact society, healthcare systems and patients and that, if authorized or approved by regulatory agencies, LENZ, a variant-agnostic immunomodulatory antibody, could address a significant unmet need in COVID-19 for the foreseeable future. Humanigen made significant progress in developing lenzilumab over the last year, highlighted by the completion of our phase 3 study of lenzilumab in COVID-19, LIVE-AIR, and the publication of positive results from the study in The Lancet Respiratory Medicine, a world-renowned, peer-reviewed journal.”

Monoclonal antibodies have been a key tool in the fight against COVID-19, since the FDA granted EUA for Regeneron’s casirivimab and imdevimab in November 2020. In January, the FDA limited use of that treatment along with bamlanivimab and etesevimab after data showed they were unlikely to be effective against the Omicron variant.