Eli Lilly and Incyte’s Baricitinib Receives FDA EUA for Use as Monotherapy in Hospitalized COVID-19 Patients Requiring Oxygen

The US Food and Drug Administration (FDA) has broadened the emergency use authorization (EUA) for baricitinib, a JAK1/JAK2 inhibitor licensed to Eli Lilly and Company (Indianapolis, Ind, USA) from Incyte (Wilmington, DE, USA), to allow for treatment with or without Gilead Sciences’ (Foster City, CA, USA) antiviral drug remdesivir.

The EUA was previously restricted to use only in combination with remdesivir and now provides for the use of baricitinib for treatment of COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Baricitinib is a janus kinase inhibitor, which blocks the activity of one or more of a specific family of enzymes, interfering with the pathway that leads to inflammation. Baricitinib is a prescription oral tablet medication that is FDA-approved (and sold under the brand name Olumiant) for the treatment of moderately to severely active rheumatoid arthritis.

The FDA based its decision on data from the Phase 3 COV-BARRIER randomized, double-blind, placebo-controlled study of hospitalized patients comparing baricitinib 4 mg once daily plus standard of care versus placebo plus standard of care. Patients could remain on background standard of care, as defined per local guidelines, including antimalarials, antivirals, corticosteroids, and/or azithromycin. The most frequently used therapies were corticosteroids (79% of patients, mostly dexamethasone) and remdesivir (19% of patients). While the composite primary endpoint of COV-BARRIER, which was defined as a difference in the estimated proportion of participants progressing to non-invasive ventilation including high flow oxygen or invasive mechanical ventilation (including ECMO) or death by Day 28, did not meet statistical significance, baricitinib-treated patients (27.8%) were less likely than those receiving standard of care (30.5%) to progress to ventilation or death. A pre-specified key secondary endpoint showed baricitinib, in addition to standard of care, meaningfully reduced the risk of death by 39 percent by Day 28 when compared to standard of care alone.

The initial EUA was based on data from the Adaptive COVID-19 Treatment Trial (ACTT-2), a randomized double-blind, placebo-controlled study to evaluate the efficacy and safety of baricitinib in combination with remdesivir versus placebo with remdesivir in hospitalized patients with or without oxygen requirements conducted by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Data supporting the initial EUA included the primary endpoint of median time to recovery, which was seven days for baricitinib plus remdesivir compared to eight days for placebo plus remdesivir. Secondary endpoints included the proportion of patients who died or progressed to non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation by Day 29, which was lower in baricitinib plus remdesivir (23%) compared to placebo plus remdesivir (28%), and the proportion of patients who died by Day 29 was 4.7% (24/515) for baricitinib plus remdesivir versus 7.1% (37/518) for placebo plus remdesivir.

"Baricitinib in combination with remdesivir has already provided many people with a treatment option that could help prevent progression to ventilation or death and increase recovery speed for certain hospitalized patients with COVID-19 under its currently authorized use," said Ilya Yuffa, senior vice president and president of Lilly Bio-Medicines. "Today's FDA action provides physicians additional treatment regimen options for baricitinib to continue to meet the urgent medical needs posed by this pandemic. Based on the increasing body of evidence, we are confident in the potential of baricitinib as an important treatment for the hospitalized COVID-19 patient population requiring supplemental oxygen."

"Recent clinical data have helped improve our understanding of the potential role of baricitinib in the treatment of certain hospitalized patients with COVID-19 and the broadened EUA represents a critical step in fighting the pandemic," said E. Wesley Ely, M.D., M.P.H., professor of medicine and co-director of the Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center at Vanderbilt University Medical Center and co-principal investigator of COV-BARRIER.

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