Lilly and Incyte announced results from a phase 3 study investigating baricitinib plus standard of care (SoC) in hospitalized patients with COVID-19.
The global, randomized, double-blind, placebo-controlled COV-BARRIER study (ClinicalTrials.gov: NCT04421027) compared the efficacy and safety of baricitinib to placebo, in addition to SoC, in 1525 adults hospitalized with COVID-19 who required supplemental oxygen (ordinal scale [OS] 5) or high-flow oxygen/noninvasive ventilation (OS 6). Patients were randomly assigned 1:1 to receive baricitinib 4mg or placebo plus SoC for up to 14 days or until hospital discharge.
The primary endpoint was the proportion of patients who progressed to the first occurrence of noninvasive ventilation (including high flow oxygen) or invasive mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) or death by day 28.
Findings showed that the trial did not meet statistical significance on the primary endpoint. Compared with placebo, baricitinib-treated patients were 2.7% less likely to progress to ventilation or death (odds ratio [OR]: 0.85; 95% CI, 0.67-1.08; P =.18). However, among patients treated with baricitinib, there was a 38% reduction in death from any cause by day 28 compared with placebo (hazard ratio [HR]: 0.57; 95% CI, 0.41-0.78; nominal P =.0018).
Moreover, the baricitinib treatment arm showed a numerical reduction in mortality for all baseline severity subgroups, with the greatest reduction observed in patients receiving noninvasive mechanical ventilation at baseline (17.5% for baricitinib vs 29.4% for placebo; HR: 0.52; 95% CI, 0.33-0.80; nominal P =.0065). There was also a reduction in mortality observed for the prespecified subgroups being treated with or without corticosteroids at baseline.
As for safety, the baricitinib and placebo treatment arms demonstrated a similar incidence of adverse events (44.5% vs 44.4%, respectively) and serious adverse events (14.7% vs 18.0%, respectively). The frequency of serious infections and venous thromboembolism (VTE) was 8.5% and 2.7% with baricitinib, respectively, compared with 9.8% and 2.5% with placebo.
“While COV-BARRIER did not hit the primary endpoint based on stages of disease progression, the data show that baricitinib meaningfully reduced the risk of mortality above and beyond the recommended standard of care, without additional safety risks. These important findings advance our pursuit of treatment options to save lives in hospitalized COVID-19 patients,” said co-primary investigator E. Wesley Ely, MD, MPH, professor of medicine and co-director of the Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center at Vanderbilt University Medical Center.
In November 2020, the Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to baricitinib, in combination with remdesivir, for the treatment of suspected or confirmed COVID-19 in hospitalized adults and pediatric patients aged 2 years and older requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.
Baricitinib, a Janus kinase (JAK) inhibitor, is currently marketed under the trade name Olumiant (Eli Lilly) for the treatment of rheumatoid arthritis.
Lilly and Incyte announce results from the phase 3 COV-BARRIER study of baricitinib in hospitalized COVID-19 patients. [press release]. Indianapolis, IN: Eli Lilly and Company; April 8, 2021.