FDA broadens existing emergency use of Lilly and Incytes baricitinib in patients hospitalized with COVID-19 requiring oxygen

Eli Lilly and Company and Incyte announced the U.S. FDA has broadened the EUA for baricitinib to allow for treatment with or without remdesivir, whereas the EUA was previously restricted to use only in combination with remdesivir. The EUA 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 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.”

The FDA based today’s decision on data from the Phase 3 COV-BARRIER study, announced April 8, 2021. COV-BARRIER was a 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 (odds ratio [OR]: 0.85; 95% CI: 0.67, 1.08; p=0.180). 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 (n/N: 62/764 [8.1%] baricitinib, 101/761 [13.3%] placebo; [estimated difference in Day 28 probability of mortality = -4.9% (95% CI: -8.0%, -1.9%); hazard ratio [HR] = 0.56 (95% CI: 0.41, 0.77)]. No new safety signals potentially related to the use of baricitinib were identified. The study findings have been submitted to a peer-reviewed journal for future print publication.

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 (HR: 1.15; 95% CI: 1.00, 1.31; p=0.047). 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%) (OR: 0.74; 95% CI: 0.56, 0.99; p=0.039), and the proportion of patients who died by Day 29 was 4.7 percent (24/515) for baricitinib plus remdesivir versus 7.1 percent (37/518) for placebo plus remdesivir (Kaplan Meier estimated difference in Day 29 probability of mortality: -2.6% [95% CI: -5.8%, 0.5%]).

“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.

The FDA grants emergency use authorization to provide availability of a medicine that may help diagnose, treat or prevent a life-threatening disease when no adequate and approved alternatives are available. This use of baricitinib is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use, unless the declaration is terminated or authorization revoked sooner. The authorization is temporary and does not replace the formal review and approval process. In the U.S., baricitinib has not been approved by the FDA to treat COVID-19, and the efficacy, safety and optimal duration of treatment of baricitinib for COVID-19 has not been established. Evaluation of baricitinib’s efficacy and safety as a treatment for COVID-19 is ongoing in clinical trials. Essential safety information on the authorized emergency use of baricitinib includes warnings related to serious infections, thrombosis, abnormal laboratory values, vaccinations and hypersensitivity. Serious side effects observed in COVID-19 patients include serious venous thrombosis and serious infections. Additional safety information can be viewed below.

In December 2020, Lilly initiated an addendum to the COV-BARRIER study to evaluate baricitinib in mechanically ventilated patients (ordinal scale 7) at baseline. The study is currently ongoing with data expected in the coming months. In addition, baricitinib is being tested in the NIH-led ACTT-4 study, UK’s RECOVERY Trial, EU-SolidAct Trial and other investigator-initiated research to further our understanding of how baricitinib may help certain hospitalized COVID-19 patients.

Under the EUA, inpatient pharmacies in the U.S. may order 1-mg and 2-mg tablets of baricitinib through Lilly’s authorized distributors. More details about the baricitinib EUA are available here or by contacting Lilly’s 24-hour support line at 1-855-LillyC19 (1-855-545-5921).

Lilly is committed to collaborating with governments, hospitals and payers to provide access to baricitinib for certain hospitalized patients with COVID-19. To date, more than 325,000 patients globally are estimated to have been treated with baricitinib for COVID-19.

Baricitinib is an oral JAK inhibitor discovered by Incyte and licensed to Lilly. For media resources, including product images and fact sheets, please click here.

Authorized Use Under the EUA and Important Safety Information for baricitinib (in the United States) for COVID-19

Baricitinib is authorized for use under an Emergency Use Authorization (EUA) for treatment of COVID-19 in hospitalized adults and pediatric patients 2 years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib has not been approved for the treatment of COVID-19, but has been authorized for emergency use by the FDA. Baricitinib is authorized under an EUA only for the duration of the declaration that circumstances exist justifying the authorization of the EUA of baricitinib under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.

For more information about the authorized use of baricitinib in COVID-19 and mandatory requirements of the EUA, please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers and Fact Sheet for Patients, Parents and Caregivers (English) (Spanish).

Important Safety Information about baricitinib for COVID-19
The following provides essential safety information on the unapproved use of baricitinib under the Emergency Use Authorization.