Genentech announced that a phase 3 study assessing tocilizumab (Actemra®) plus standard of care for the treatment of hospitalized adults with coronavirus disease 2019 (COVID-19) associated pneumonia met its primary end point.
The multicenter, randomized, double-blind, placebo-controlled EMPACTA study included hospitalized COVID-19 patients with oxygen saturation less than 94% while on ambient air who did not require noninvasive or invasive mechanical ventilation. Patients were randomized to receive 1 intravenous infusion of tocilizumab or placebo plus standard of care, and could be given up to 1 additional infusion. The primary end point was the cumulative proportion of patients dying or requiring mechanical ventilation by day 28.
Of the 389 patients included in the study, 85% were from minority racial and ethnic groups. “We have been striving to improve inclusion and diversity in our trials,” said Jamie Freedman, MD, PhD, head of US Medical Affairs for Genentech. “During the COVID-19 pandemic, we saw how high the stakes were for many communities of color and made diversity the centerpiece of this trial.”
Results showed that patients treated with tocilizumab were 44% less likely to progress to mechanical ventilation or death compared with placebo (hazard ratio [HR] 0.56; 95% CI, 0.32-0.97; log-rank P =.0348). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the tocilizumab arm compared with 19.3% in the placebo arm.
In addition, tocilizumab was associated with a longer time to clinical failure by day 28 (secondary end point; log-rank P =.0217), defined as the time to death, mechanical ventilation, ICU admission, or withdrawal (whichever occurs first). However, this was not considered statistically significant as tocilizumab did not meet other key secondary end points including time to hospital discharge or “ready to discharge”, time to improvement in ordinal clinical status, and mortality rate.
The safety profile of tocilizumab was consistent with its known profile, and there were no new safety signals identified. The most common adverse events for tocilizumab were constipation (5.6%), anxiety (5.2%), and headache (3.2%). At day 28, the incidence of infections was 10% for tocilizumab vs 11% for placebo, and the incidence of serious infections was 5% for tocilizumab vs 6.3% for placebo.
Tocilizumab is also being investigated for COVID-19 associated pneumonia in the phase 3 REMDACTA trial, in combination with remdesivir. In July 2020, the Company announced that the phase 3 COVACTA study evaluating tocilizumab in hospitalized patients with severe COVID-19 associated pneumonia did not meet its primary and key secondary end points.
Actemra, an interleukin-6 antagonist, is currently approved for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis or active polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome.
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Genentech’s phase III EMPACTA study showed Actemra reduced the likelihood of needing mechanical ventilation in hospitalized patients with COVID-19 associated pneumonia. https://www.businesswire.com/news/home/20200917006062/en/Genentech%E2%80%99s-Phase-III-EMPACTA-Study-Showed-Actemra-Reduced-the-Likelihood-of-Needing-Mechanical-Ventilation-in-Hospitalized-Patients-With-COVID-19-Associated-Pneumonia. Accessed September 18, 2020.