New ACTT-2 data shows a marked benefit from the combination regimen versus lone remdesivir.
Remdesivir plus baricitinib was associated with a 35% decrease in mortality versus lone remdesivir among patients hospitalized with coronavirus 2019 (COVID-19), according to new ACTT-2 trial findings shared within hours of final ACTT-1 results being published to The New England Journal of Medicine.
The new data, again presented by John Beigel, MD, associate director for clinical research in the Division of Microbiology and Infectious Diseases at the National Institute for Allergy and Infectious Disease (NIAID) at the National Institutes for Health (NIH), support the indication made by ACTT-1 investigators: that remdesivir in combination with complementary agents may be more optimal for COVID-19 time to recovery and mortality risk versus a lone regimen of the antiviral therapy.
Baricitinib (Olumiant) is a JAK-1 and -2 inhibitor generally associated with the treatment of rheumatoid arthritis. Its inflammation-targeting mechanism of action led to its assessment in combined use with antiviral therapy for patients severely ill with COVID-19.
Beigel presented the newest data from ACTT-2 at the International Society for Influenza and other Respiratory Virus Diseases Antiviral Group (isirv-AVG) Virtual Conference on Thursday evening. He shared clinical outcomes indicating patients who required supplemental oxygen and those who required high-flow oxygen/non-invasive ventilation at baseline—a ‘5’ and ‘6’ on the seven-point clinical ordinal scale used to assess COVID-19 hospitalization status—experienced the most significant improvements and reduced risks in mortality.
The NIAID investigators previously reported that baricitinib plus remdesivir achieved the ACTT-2 primary endpoint of median time to recovery: a one-day, or 12.5% overall, improvement versus lone remdesivir (8 vs 7; incidence rate ratio [IRR], 1.16; 95% CI, 1.01-1.32; P = .04). Recovery was defined hospital discharge or removal from supplemental oxygen during hospital care at day 29.
In the newest data, investigators observed a 35% decrease in death among patients treated with baricitinib plus remdesivir (5.1%) versus lone remdesivir (7.8%) at day 29 (hazard ratio [HR], 0.65; 95% CI, 0.39-1.08; P = .09). As previously noted, patients receiving oxygen at baseline reported more pronounced reductions in mortality: group 5 and group 6 patients reported 60% and 43% reduced mortality risks, respectively.
Investigators reported no new safety signals among patients with COVID-19 to have received baricitinib. The team is currently working toward having complete analyses and a peer-reviewed manuscript published in the near future.
Additionally, Eli Lilly and Company are pursuing a potential Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for baricitinib, for the treatment of patients hospitalized with COVID-19.
"We are excited that these results add to the potential role for baricitinib to treat hospitalized COVID-19 patients," Ilya Yuffa, Lilly senior vice president and president of Lilly Bio-Medicines, said in a statement. "Lilly is committed to identifying impactful preventions and treatments, and we are engaged in discussions with the FDA regarding the potential to make baricitinib available to hospitalized patients as quickly as possible."