Lilly and Incyte Announce Phase 3 COV-BARRIER Results: Olumiant Plus Standard of Care Reduces Mortality by 38% in Hospitalized COVID-19 Patients Amid Global Cases Surpassing 133 Million

April 08, 2021 News /BioonBIOON/ -- At present, the COVID-19 epidemic overseas is still spreading rapidly. According to Baidu's "Real-time Data on the Novel Coronavirus Pneumonia Epidemic"Big DataReport》, as of 22:00 on April 8, 2021, the global cumulative number of confirmed cases exceeded 130 million (133.86 million), with more than 2.9 million deaths.

Recently,Eli Lilly(Eli Lilly) and its partner Incyte announced the results of the Phase 3 COV-BARRIER study (NCT04421027) evaluating the oral JAK inhibitor Olumiant (baricitinib) in hospitalized patients with COVID-19. The data showed that by Day 28, although the study did not meet its primary endpoint,Compared with placebo + standard of care (SoC, including corticosteroids and remdesivir), Olumiant + placebo reduced the risk of death by 38% (p=0.0018).

November 2020, United StatesFDAEmergency Use Authorization (EUA) Granted for Olumiant: Olumiant in combination with Veklury (remdesivir) is authorized for the treatment of hospitalized adult and pediatric patients aged 2 years and older with suspected or laboratory-confirmed coronavirus disease 2019 (COVID-19) who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The recommended dosage under the EUA is Olumiant 4 mg once daily for up to 14 days or until hospital discharge.

The active pharmaceutical ingredient of Olumiant is baricitinib, a selective, reversible JAK1 and JAK2 inhibitor administered orally once daily, currently in clinical development for various inflammatory diseases andAutoimmunityTreatment of sexually transmitted diseases, including classRheumatoid Arthritis(RA), psoriasis,DiabetesRenal Disease, Atopic Dermatitis, SystemicLupus Erythematosusetc. There are four JAK enzymes, namely JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines are involved in various inflammatory andAutoimmunityThe pathogenesis of immune-mediated diseases suggests that JAK inhibitors may be widely used to treat various inflammatory conditions. In kinase inhibition assays, baricitinib demonstrated 100-fold greater inhibitory potency against JAK1 and JAK2 than against JAK3.

Eli LillyReached an exclusive collaboration agreement with Incyte in 2009 to jointly develop Olumiant and certain follow-on compounds. To date, Olumiant has been approved in more than 70 countries and regions worldwide (including the United States, the European Union, and Japan) for the treatment of moderate-to-severe active rheumatoid arthritisRheumatoid Arthritis(RA) adult patients. In November 2020, Olumiant received EU approval for a new indication for the treatment of moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy.

COV-BARRIER was the first global, randomized, double-blind, placebo-controlled study to evaluate the efficacy of the oral JAK inhibitor Olumiant (baricitinib) in combination with standard of care (SoC) for the treatment of hospitalized patients with COVID-19. SoC could include corticosteroids, antimalarial drugs, antiviral agents, and/or azithromycin. The study was initiated in June 2020 and enrolled 1,525 hospitalized patients who required no supplemental oxygen (Ordinal Scale [OS] score of 4), required supplemental oxygen (OS 5), or required high-flow oxygen/non-invasive ventilation (OS 6). These patients also needed to have at least one elevated inflammatory marker, indicating a risk of disease progression.

In accordance with local clinical practice, all patients received standard of care (SoC) treatment, including corticosteroids in 79% of patients (of whom 91% received dexamethasone) and remdesivir at baseline in 19% of patients; some patients received both therapies. In the study, patients were randomized in a 1:1 ratio to receive once-daily oral Olumiant 4 mg or placebo for 14 days or until hospital discharge.

This is a global study involving diverse patients from multiple high-incidence countries, including the United States, Brazil, Mexico, Argentina, Russia, India, the United Kingdom, Spain, Italy, Germany, Japan, and South Korea. A supplement to this study was initiated in December 2020 to enroll patients receiving mechanical ventilation at baseline (OS 7), and enrollment is currently ongoing.

The results showed that the study did not achieve statistical significance for the primary endpoint. The primary endpoint was defined as the proportion of patients whose condition progressed to require first-time non-invasive ventilation (including high-flow oxygen), invasive mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]), or death by Day 28. Compared with the placebo + standard of care (SoC) group, the Olumiant + SoC group had a 2.7% lower likelihood of progressing to ventilation (non-invasive or mechanical) or death; this difference was not statistically significant (odds ratio [OR] = 0.85; 95% CI: 0.67–1.08; p = 0.1800).

It is worth noting that,By Day 28, treatment with Olumiant + SoC significantly reduced all-cause mortality by 38% compared with placebo + SoC (nominal p-value = 0.0018; Olumiant group: 62/764 [8.1%], placebo group: 100/761 [13.1%]; hazard ratio [HR] = 0.57; 95% CI: 0.41, 0.78).In all baseline severity subgroups of patients treated with Olumiant, a numerical reduction in mortality was observed, which was most pronounced in patients receiving non-invasive mechanical ventilation at baseline (mortality rate: 17.5% in the Olumiant + SoC group vs. 29.4% in the placebo + SoC group; hazard ratio [HR] = 0.52; 95% CI: 0.33, 0.80; nominal p-value = 0.0065). Mortality was also reduced in the prespecified subgroups of patients receiving or not receiving corticosteroid therapy at baseline.

In the study, the incidence rates of adverse events and serious adverse events were broadly similar between the Olumiant group (44.5% and 14.7%, respectively) and the placebo group (44.4% and 18.0%, respectively). The incidence rates of serious infections and venous thromboembolism (VTE) were 8.5% and 2.7%, respectively, in the Olumiant group, compared with 9.8% and 2.5%, respectively, in the placebo group. No new safety signals potentially related to the use of Olumiant were identified.

Eli Lilly plans to publish the detailed results of this study in a peer-reviewed journal in the coming months.Eli LillyData from the COV-BARRIER study will be shared with regulatory authorities in the United States, the European Union, and other regions to evaluate next steps for the use of Olumiant in treating hospitalized patients with COVID-19.

E. Wesley Ely, M.D., Professor of Medicine and Co-Director of the Center for Critical Illness, Brain Dysfunction, and Survival (CIBS) at Vanderbilt University Medical Center, who served as a co-investigator in the COV-BARRIER study, stated, “There remains an unmet medical need for therapies with the potential to further reduce mortality among patients with COVID-19. Although the COV-BARRIER study did not meet its primary endpoint based on disease progression stages, the data demonstrated that Olumiant meaningfully reduced mortality without additional safety risks. These important findings advance our pursuit of therapeutic strategies to save the lives of hospitalized patients with COVID-19.”

Eli LillyIlya Yuffa, Senior Vice President and President of the biopharmaceutical company, stated, “Since the onset of the pandemic, we have been committed to advancing the science behind COVID-19 therapies. Although this study did not demonstrate a statistically significant benefit on the primary endpoint, the trial showed the largest reduction in mortality among COVID-19 patients reported to date. Given the ongoing urgent need to reduce COVID-related deaths in hospitalized patients, we hope these findings will further elucidate and support the potential role of Olumiant as a treatment adjunct to the current standard of care.” (Bioon.com)

Original Source: Lilly and Incyte Announce Results from the Phase 3 COV-BARRIER Study of Baricitinib in Hospitalized COVID-19 Patients