The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH), recently produced results from a clinical trial the research agency sponsored the ACTT-2 clinical trial formally titled, “A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults.” An adaptive randomized double-blind placebo-controlled trial evaluated the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. Involving about 100 trial site locations worldwide, the multicenter study compared different investigational therapeutic agents to the control arm. The study specifically investigated the combination of baricitinib and remdesivir as compared to remdesivir alone in 1,033 patients. The investigators found that baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, especially among individuals receiving high-flow oxygen or noninvasive ventilation. Additionally, the combination of the two therapies involved fewer serious adverse events. Baricitinib, known as Olumiant, is produced by Eli Lilly. In November, the FDA issued an emergency use authorization due to the findings associated with ACTT-2.
Known as ACTT-2, the study represented an ongoing program sponsored by NIAID and associated with ACTIV—the NIH Foundation’s Accelerating COVID-19 Therapeutic Interventions and Vaccines. The study (NCT04401579) started May 8 and ran through July 31, 2020. With findings published in the New England Journal of Medicine, the study team showcased how out of a total of 1,033 patients, 515 assigned were to the combination therapy and 518 to the control, those who received both baricitinib and remdesivir had a median time to recovery of 7 days (95% CI, 6 to 8) as compared with 8 days (95% CI, 7 to 9) with control (rate of ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P=0.03), and a 30% greater chance of improvement in clinical status by day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). The study team reported in their NEJM findings that those participants receiving high-flow oxygen or noninvasive ventilation at enrollment experienced a time to recovery of 10 days with combination treatment and 18 days with control (ratio for recovery, 1.51; 95% CI, 1.10 to 2.08).
28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09); while serious adverse events were reported less in the combination group than in the control group (see source for figures).
Importance of Drug Repurposing
It’s widely known by the medical community that the repurposing of existing, known drugs can expedite new drug development. Hence the importance of this study as Baricitinib, approved to treat rheumatoid arthritis, was reported back in June in the journal EMBO Molecular Medicine that evidence indicated the drug had antiviral and anti-inflammatory properties demonstrating an ability to reduce viral load and inflammation associated with COVID-19.
While Remdesivir was controversially approved on an emergency basis back in May based on a NIAID-sponsored study. In that study the federal research agency approved the change of endpoint measurements toward the end of the study—from mortality rate (which had no positive findings) to reduction in duration of illness. Published in the New England Journal of Medicine, the study evidenced that the antiviral drug reduced recovery time to 10 days (versus 15 days for those on the placebo).
Consequently, Remdesivir was approved by the U.S. FDA for hospitalized COVID-19 patients in October. Importantly, due to data generated in the Solidarity study, the World Health Organization recommends against Remdesivir: they argue the drug isn’t effective against COVID-19.