Tocilizumab was found ineffective in its first phase 3 trial in treatment of adults hospitalised with severe COVID-19–associated pneumonia reported Genentech. The company said that the tocilizumab did not meet its primary endpoint of improving clinical status or key secondary endpoints, including a difference in patient mortality at week 4.
Tocilizumab, also known as atlizumab, is an immunosuppressive drug, mainly used for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. It is a humanised monoclonal antibody against the interleukin-6 receptor. The drug was recommended by the Indian Council for Medical Research (ICMR) for emergency use in treating COVID-19 patients. It was indicated for patients with moderate disease with progressively increasing oxygen requirements and in mechanically ventilated patients not improving despite the use of steroids.
The randomized, double-blind COVACTA trial compared tocilizumab plus standard of care (SOC) with placebo plus SOC in hospitalised patients with severe COVID-19 pneumonia. The primary endpoint of clinical status was measured by a seven-category ordinal scale, which tracked patients’ clinical status based on their need for intensive care and/or ventilator use and supplemental oxygen requirements. The study was conducted in collaboration with the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, with study locations in the United States, Canada and Europe.
The findings showed that the difference in clinical status at week 4 between patients treated with tocilizumab and those given placebo was not statistically significant (P=0.36). There also was no difference between tocilizumab and placebo in the percentage of patients who died by week 4 (tocilizumab, 19.7% and placebo, 19.4%; difference, P=0.9410).
However, the median time to hospital discharge, or “ready to discharge,” was shorter in patients treated with tocilizumab, at 20 days compared with 28 days with placebo (P=0.0370). However, the researchers highlighted that the difference could not be considered statistically significant as the primary endpoint was not met.
The difference in ventilator-free days between tocilizumab and placebo was not statistically significant (median, 22 days with tocilizumab and 16.5 days with placebo; P=0.3202). At week 4, rates of infections and serious infections were 38.3% and 21.0% in the tocilizumab arm and 40.6% and 25.9% in the placebo arms. The most common adverse events in patients who received tocilizumab included hypertension (6.4%), acute kidney injury (5.8%) and diarrhea (5.8%). The COVACTA study did not identify any new safety signals for tocilizumab.
The company said that it has initiated several other studies to investigate tocilizumab as a potential treatment for patients with COVID-19–associated pneumonia, including two phase 3 clinical trials, REMDACTA and EMPACTA, as well as the phase 2 MARIPOSA trial. There also are a number of independent trials of tocilizumab in this setting.