The treatment of severe Covid-19 has proven difficult over the past three years, illustrated most clearly by the lack of approved drugs to treat the disease. Recently, the Food and Drug Administration has just its third fully approved treatment, joining Baricitinib and Remdesivir. Baricitinib is approved for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). In contrast, Remdesivir is approved for all patients with mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death.
Tocilizumab, branded Actemra by pharmaceutical company Genentech, is a monoclonal antibody now approved for treating Covid-19 in hospitalized adult patients who receive systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), akin to Barcitinib. All treatments to this point of the pandemic were only temporarily approved via emergency use authorization. In a previous article, we discussed the antibody’s discovery and mechanism of action. Here we discuss how Tocilizumab treats those suffering from moderate to severe Covid-19.
Chief among Covid-19 symptoms are inflammatory conditions such as body pains, headaches, fatigue, and others. Recent studies even link long-term Covid-19 inflammation to permanently impacting the lungs, kidneys, and brain. Treating inflammation in moderate to severe Covid-19 patients could quell both short and long-term consequences of infection.
As a highly active anti-inflammatory monoclonal antibody treatment used for over ten years to treat Castleman’s disease, rheumatoid arthritis, and other forms of chronic inflammation, Tocilizumab was a prime candidate for treating Covid-19 inflammation. Tocilizumab is an IL-6 inhibitor, a secreted cytokine protein expressed by white blood cells. In terms of disease, IL-6 stimulates inflammatory processes when the body is exposed to various pathogens and clinical conditions such as diabetes, multiple sclerosis, and rheumatoid arthritis.
Both the emergency use authorization issued for Tocilizumab in June 2021 and the recent full approval by the Food and Drug Administration were based on the University of Oxford-led trial RECOVERY and supported by Genentech-sponsored trial EMPACTA.
In the RECOVERY trial, 4,116 adults with progressive Covid-19 (defined as oxygen saturation <92% on room air or receiving oxygen therapy, and CRP ≥75 mg/L) received either the current standard of care or Tocilizumab treatment in addition to the current standard of care. Most patients also received systemic corticosteroids at the start of their disease progression.
The cohort who received Tocilizumab had a mortality rate of 30.7%, whereas those who only received the standard of care had a mortality rate of 34.9%. Therefore the reduced risk of death from Covid-19 for those who received the drug was -4.1%.
Notably, those who received systemic corticosteroids in addition to Tocilizumab saw even more robust results. Their reduced risk of death was -5.9%, suggesting the drug should be administered alongside corticosteroids in Covid-19 patients. We note that these are somewhat marginally positive reductions in the risk of death for a drug to receive full approval.
The EMPACTA study delivered similarly modest results in a smaller 389-patient study. 12% of those receiving the drug required ventilation or died, whereas 19.3% of those receiving the placebo required ventilation or died.
On Wednesday, December 21st, Genentech announced that Acterma, the clinical name for Tocilizumab, was fully approved for use in hospitalized adults. It joins Baricitinib as an approved treatment solely for hospitalized adults and Remdesivir, which remains the only approved drug for all ages.
The emergency use authorization for Tocilizumab remains, allowing hospitalized patients as young as two years old to receive the drug.
Currently, there are three fully approved drugs and 13 treatments approved via emergency use authorization. The marginal effect of Tocilizumab and the recent withdrawal of some antibody treatments from the Emergency Use Authorization list outlines the research difficulty for Covid-19 antivirals. This underlines the necessity to continue expanding our search for highly effective, safe, long-acting antiviral drugs that can be used singularly or combined to prevent and treat Covid-19.