LILLY AND INCYTE ANNOUNCE RESULTS FROM THE PHASE 3 COVBARRIER STUDY OF BARICITINIB IN HOSPITALISED COVID-19 PATIENTS

LILLY AND INCYTE ANNOUNCE RESULTS FROM THE PHASE 3 COVBARRIER

STUDY OF BARICITINIB IN HOSPITALISED COVID-19 PATIENTS

 Randomised, double-blind, placebo-controlled study of 1,525 patients did not meet statistical significance on primary endpoint

(progression to non-invasive ventilation or invasive mechanical ventilation or death)

 Data showed 38% reduction in mortality by Day 28 (nominal p-value=0.0018) in patients treated with baricitinib in

addition to standard of care, including corticosteroids and remdesivir

BASINGSTOKE, April 8, 2021 – Eli Lilly and Company announced today the results of COVBARRIER,

a Phase 3 study evaluating baricitinib 4 mg once daily plus standard of care (SoC)

versus placebo plus SoC. The trial did not meet statistical significance on the primary endpoint,

which was defined as a difference in the proportion of participants progressing to the first

occurrence of non-invasive ventilation including high flow oxygen or invasive mechanical

ventilation including extracorporeal membrane oxygenation (ECMO) or death by Day 28.

Baricitinib-treated patients were 2.7 percent less likely than those receiving standard of care to

progress to ventilation (non-invasive or mechanical) or death, a difference that was not

statistically significant (odds ratio [OR]: 0.85; 95% CI 0.67, 1.08; p=0.1800).

In COV-BARRIER, treatment with baricitinib in addition to SoC (which included 79% receiving

corticosteroids and 19% receiving remdesivir, with some receiving both) resulted in a significant

reduction (nominal p-value=0.0018) in death from any cause by 38 percent (n/N: 62/764 [8.1%]

baricitinib, 100/761 [13.1%] placebo; hazard ratio [HR]: 0.57; 95% CI: 0.41, 0.78) by Day 28. A

numerical reduction in mortality was observed for all baseline severity subgroups of baricitinibtreated

patients and was most pronounced for patients receiving non-invasive mechanical

ventilation at baseline (17.5% versus 29.4% for baricitinib plus SoC versus SoC; hazard ratio

[HR]: 0.52; 95% CI: 0.33, 0.80; nominal p-value=0.0065). A reduction in mortality was also seen

for the pre-specified subgroups of patients being treated with or without corticosteroids at

baseline.

“There remains a driving unmet need for treatments with the potential to further decrease

mortality for COVID-19 patients,” said co-primary investigator E. Wesley Ely, M.D., MPH,

professor of medicine and co-director of the Critical Illness, Brain Dysfunction, and

Survivorship (CIBS) Center at Vanderbilt University Medical Center. “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 hospitalised COVID-19 patients.”

The frequency of adverse events and serious adverse events were generally similar in the

baricitinib (44.5% and 14.7%, respectively) and placebo (44.4% and 18.0%, respectively) groups.

Serious infections and venous thromboembolism (VTE) occurred in 8.5 percent and 2.7 percent

of patients treated with baricitinib, respectively, versus 9.8 percent and 2.5 percent of patients

treated with placebo. No new safety signals potentially related to the use of baricitinib were

identified.

Lilly intends to publish detailed results of this study in a peer-reviewed journal in the coming

months. Lilly will share the data from COV-BARRIER with regulatory authorities in the U.S.,

European Union and other geographies to evaluate next steps for baricitinib for the treatment of

hospitalised COVID-19 patients.

“Since the beginning of the pandemic, we have worked to expand the science behind COVID-19

therapies,” said Ilya Yuffa, senior vice president and president of Lilly Bio-Medicines. “Even

though the study did not show a statistically-significant benefit on the primary endpoint, this trial

showed the largest effect reported to date for reduction in mortality observed for this patient

population with COVID-19. As there remains an urgent need to reduce COVID-related deaths

in hospitalised patients, we hope these results will provide further understanding and support for

baricitinib’s potential role in treatment on top of the current standard of care.”

COV-BARRIER (NCT04421027) is the first global, randomised, double-blind, placebocontrolled

study to assess baricitinib versus placebo in patients hospitalised with COVID-19 receiving SoC which could include corticosteroids, antimalarials, antivirals, and/or azithromycin.

This Phase 3 study of 1,525 patients began in June 2020 and enrolled hospitalised patients who

did not require supplemental oxygen (ordinal scale [OS] 4), required supplemental oxygen (OS 5)

or high-flow oxygen/non-invasive ventilation (OS 6). Patients were also required to have at least

one increased marker of inflammation, an indicator of risk of disease progression. All patients

were treated with SoC per local clinical practice including 79 percent receiving corticosteroids

(with 91% of those patients receiving dexamethasone) and 19 percent receiving remdesivir at

baseline, with some receiving both. Patients were randomised 1:1 to baricitinib 4 mg or placebo

for up to 14 days or until discharge from the hospital. The study was global and included diverse

patients from several countries with high prevalence of COVID-19 hospitalizations – the U.S.,

Brazil, Mexico, Argentina, Russia, India, UK, Spain, Italy, Germany, Japan and Korea. An

addendum to the study was initiated in December 2020 to include mechanically ventilated (OS 7)

patients at baseline and is currently enrolling.

Additional research is ongoing to further evaluate the potential role of baricitinib in COVID-19,

including NIAID’s ACTT-4 trial (evaluating the efficacy and safety of baricitinib or

dexamethasone in combination with remdesivir in hospitalised adults with COVID-19 on

supplemental oxygen), the RECOVERY trial being run by the University of Oxford and several

investigator-initiated trials.