Tocilizumab Flops in Late-Stage Trial for COVID-19–Related Pneumonia

Roche’s arthritis drug tocilizumab failed to meet the primary and secondary endpoints in COVACTA, a randomized, phase 3 trial of COVID-19 patients hospitalized with pneumonia, the company announced.

The results of the COVACTA trial follow those of an Italian trial of tocilizumab—marketed as Actemra/RoActemra—that found no difference between tocilizumab versus placebo in intensive care requirements or mortality.

Despite the results of the Italian trial, Roche moved ahead with its own COVACTA study.

The COVACTA trial randomized hospitalized COVID-19 patients with associated pneumonia to receive standard of care plus either intravenous tocilizumab or placebo. The primary outcome was improved clinical status, measured using a seven-category ordinal scale to assess clinical status per intensive care needs and/or ventilator use and supplemental oxygen needs, over a four-week period. Secondary outcomes included four-week mortality.

COVACTA enrolled 450 patients. Differences in the primary outcome were not statistically significant between the tocilizumab versus placebo groups (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.81 to 1.76; P=0.36). At week four, mortality rates did not largely differ between the treatment versus placebo groups (19.7% vs. 19.4%; difference, 0.3%; 95% CI, -7.6% to 8.2%; P=0.9410). The difference in median number of ventilator-free days between the tocilizumab versus placebo groups did not reach statistical significance (22 days vs. 16.5 days; difference, 5.5 days; 95% CI, -2.8 to 13.0 days; P=0.3202). Four-week infection rates were 38.3% in the tocilizumab group and 40.6% in the placebo group, and serious infection rates were 21.0% and 25.9%, respectively. No new safety signals were observed for tocilizumab.

Although COVACTA’s primary endpoint was not met, the tocilizumab group had a shorter median time to hospital discharge or “ready to discharge” than the placebo group (20 days [95% CI, 17.0 to 27.0 days] vs. 28 days [95% CI, 20.0 to NE days]; P=0.0370). But because the main endpoint was not achieved, the difference could not be considered to have met statistical significance.

“People around the world are waiting for further effective treatment options for COVID-19 and we are disappointed that COVACTA did not demonstrate a benefit for patients in either clinical status or mortality at week four. We will continue to generate evidence to provide a more complete understanding of Actemra/RoActemra in COVID-19 associated pneumonia,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release.

“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 rigour. We will keep working to help combat the COVID-19 pandemic.”