Roche’s Actemra failed to meet its primary and secondary endpoints in a late-stage study involving hospitalized patients with severe COVID-19 associated pneumonia. The drug also failed to hit a key secondary endpoint of reduced patient mortality.
Genentech, the South San Francisco-based Roche subsidiary, launched the Phase III COVACTA study of Actemra, a rheumatoid arthritis drug, in March for this indication. The COVACTA study marked the first global study of Actemra (tocilizumab) plus standard-of-care in this setting. Actemra is an IL-6 inhibitor. The IL-6 protein triggers the body’s immune and inflammatory response to fight infections. But, in the case of those patients where their immune system overreacts, such as in some COVID-19 patients, inhibiting IL-6 could keep the body from attacking itself.
This morning, Genentech announced that COVACTA did not meet its primary endpoint of improved clinical status in hospitalized adult patients with severe COVID-19 associated pneumonia. In addition, the key secondary endpoints, which included the difference in patient mortality at week four, were not met. However, there was a positive trend in time to hospital discharge in patients treated with Actemra, the company said. The median time to discharge for Actemra patients was 20 days, compared to 28 days for placebo patients. Genentech did say, however, that the difference cannot be considered statistically significant as the primary endpoint of the COVACTA study was not met.
The COVACTA study, which was conducted in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), did not identify any new safety signals for Actemra. Further analysis of the trial results is needed to fully understand the data. The results will be submitted for publication in a peer-reviewed journal.
Levi Garraway, chief medical officer and head of Global Product Development for Roche, expressed his disappointment at the trial’s failure. As COVID-19, the disease caused by the novel coronavirus, continues to sweep across the globe infecting millions, Garraway said people are waiting for effective treatment options for the disease.
“We will continue to generate evidence to provide a more complete understanding of Actemra in COVID-19 associated pneumonia,” Garraway said in a statement. “We are grateful for the patients and physicians around the world who helped us to complete this study quickly during a public health crisis, while upholding the highest standards of scientific rigor. We will keep working to help combat the COVID-19 pandemic.”
The failure of Actemra in this setting follows the failure of another IL-6 inhibitor in COVID-19. Earlier this month, Regeneron and Sanofi announced that its Phase III study of Kevzara in COVID-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints. The trial was stopped following those results, although the companies said they did observe some “minor positive trends” in the primary pre-specified analysis group.
Despite the failure of the Phase III study, Genentech said it remains committed to continuing the Actemra clinical trial program in COVID-19 to further explore Actemra in other treatment settings, including in combination with an antiviral. In addition to COVACTA, Genentech has initiated several studies to further investigate Actemra as a potential treatment for patients with COVID-19 associated pneumonia, including two Phase III clinical trials, REMDACTA and EMPACTA, as well as the Phase II MARIPOSA trial. There are a number of independent trials of Actemra in this setting.