FDA approves Actemra for emergency use in hospitalised COVID-19 patients
The monoclonal antibody Actemra (tocilizumab) was approved for emergency use in hospitalised paediatric and adult COVID-19 patients based on results from four clinical trials.
The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for Genentech’s Actemra (tocilizumab) for the treatment of hospitalised adults and paediatric patients (aged 2 years and over) who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Actemra is not authorised for use in outpatients with COVID-19.
The approval was based on the results of multiple clinical trials including Randomised Evaluation of COVID-19 Therapy (RECOVERY) – a randomised, controlled, open-label, platform trial – and three randomised, double-blind, placebo-controlled trials (EMPACTA, COVACTA and REMDACTA).
In the RECOVERY trial, 4,116 hospitalised patients with severe COVID-19 pneumonia were randomised to receive either Actemra in addition to usual care (2,022 patients) or usual care alone (2,094 patients). The primary endpoint evaluated death through 28 days of follow-up, by day 28 the probability of death for Actemra recipients was estimated to be 30.7 percent, statistically significant from 34.9 percent for patients receiving usual care alone. The median time to hospital discharge was 19 days for patients receiving Actemra and >28 days for patients receiving usual care.
In the EMPACTA trial, 389 hospitalised patients with COVID-19 pneumonia were randomised to receive Actemra (249 patients) or placebo (128 patients). The primary endpoint evaluated the need for mechanical ventilation or death through 28 days of follow-up. There was an observed reduction in progression to mechanical ventilation or death in patients receiving Actemra and the primary analysis results were statistically significant. The proportion of patients who required mechanical ventilation or died by day 28 was estimated to be 12.0 percent for patients receiving Actemra and 19.3 percent for patients receiving placebo.
In the COVACTA trial, 452 hospitalised patients with severe COVID-19 pneumonia were randomised to receive Actemra (294 patients) or placebo (144 patients). The primary endpoint was clinical status through 28 days of follow-up assessed on a seven-category ordinal scale. There was no statistically significant difference observed in clinical status on the seven-category ordinal scale at day 28 between treatment groups.
In the REMDACTA trial, 649 hospitalised patients with severe COVID-19 pneumonia were randomised to receive Actemra in combination with remdesivir (430 patients) or placebo in combination with remdesivir (210 patients). The primary endpoint was time to hospital discharge or “ready for discharge” through 28 days of follow-up. There were no statistically significant differences observed between treatment groups with respect to time to hospital discharge or “ready for discharge” through 28 days of follow-up.
Actemra is a monoclonal antibody that reduces inflammation by blocking the interleukin-6 (IL-6) receptor, rather than interacting with SARS-CoV-2 (the virus that causes COVID-19). COVID-19 can cause the immune system to become hyperactive, worsening symptoms of the disease. Actemra is a prescription medication given by intravenous infusion that is FDA-approved for multiple inflammatory diseases, including rheumatoid arthritis.
“Today’s action demonstrates the FDA’s commitment to making new therapies available through every stage of the global COVID-19 pandemic,” stated Dr Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research. “Although vaccines have been successful in decreasing the number of patients with COVID-19 who require hospitalisation, providing additional therapies for those who do become hospitalised is an important step in combating this pandemic.”
An EUA is different to an FDA approval. An EUA allows medicines that have not been formally approved to be administered in during an emergency. It is based on whether the totality of available scientific evidence suggests the known or potential risks of the product outweigh any known or potential benefits. Based on the FDA’s review of the evidence available, the agency has determined that it is reasonable to believe that Actemra may be effective in treating COVID-19 for the authorised population and, when used to treat COVID-19 for the authorised population, the known and potential benefits of Actemra outweigh the known and potential risks for the drug.