Eli Lilly Launches Phase 3 Trial of JAK1/2 Inhibitor Olumiant (Baricitinib) for Cytokine Storm in Hospitalized COVID-19 Patients Amid Global Surge to Over 8.1 Million Cases

June 16, 2020 /Bio ValleyBIOON/ -- At present, the COVID-19 epidemic overseas continues to spread rapidly. According to Baidu's "Real-time Data on the Novel Coronavirus Pneumonia Epidemic"Big DataReport》As of 18:00 on June 16, 2020, the global cumulative number of confirmed cases exceeded 8.137 million, with 8.052 million cumulative confirmed cases and 434,000 deaths outside China.

The COVID-19 pandemic has reached an unprecedented level of severity, prompting governments worldwide to issue emergency authorizations for the use of promising drugs and therapies in the treatment of severe COVID-19 cases, including antiretroviral agents, antimalarial drugs, anti-inflammatory medications, and convalescent plasma. Currently, numerous pharmaceutical companies have joined the effort to develop drugs and vaccines for Coronavirus Disease 2019 (COVID-19).

Recently,Eli Lilly(Eli Lilly) announced that the first patient has been enrolled in a randomized, double-blind, placebo-controlled Phase III trial evaluating the oral JAK1/JAK2 inhibitor baricitinib for the treatment of hospitalized adult patients with coronavirus disease 2019 (COVID-19). Currently, baricitinib has been approved in 70 countries worldwide and is marketed under the brand name Olumiant for the treatment of moderate to severe active rheumatoid arthritis.Rheumatoid Arthritis(RA) adult patients.

Eli LillyThis Phase III trial is expected to enroll 400 patients, with data anticipated to be released in the coming months. The study will be conducted in the United States, Europe, and Latin America, enrolling adult patients who are hospitalized due to novel coronavirus (SARS-CoV-2) infection, have at least one elevated inflammatory marker, and do not require invasive mechanical ventilation at the start of the study. In the trial, patients will be randomly assigned to receive either baricitinib or placebo for 14 days or until hospital discharge.

The primary endpoint of the study was the proportion of patients who died or required non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation within 28 days among those receiving baricitinib at a daily dose of 4 mg (plus background therapy) compared with those receiving placebo (plus background therapy). Key secondary endpoints included the proportion of patients with clinical improvement at various time points, time to recovery, length of hospital stay, ventilator-free days, and mortality during the 28-day period.

In COVID-19 infection, increased disease severity may be associated with an inflammatory state.It is speculated that,By inhibiting JAK1 and JAK2, baricitinib can reduce the cytokine storm associated with this infectious complication.。Cytokine storm is a severe hyperimmune response that can cause respiratory system damage in patients with COVID-19, leading to life-threatening respiratory complications. Furthermore, baricitinib may play a role in inhibiting host cell proteins that facilitate viral replication, thereby reducing the ability of infected cells to produce additional viruses. A manuscript accepted by the international medical journal EMBO Molecular Medicine provides a detailed account of the mechanism of action of baricitinib in the treatment of COVID-19.

Eli LillyThe Phase III trial conductedClinical TrialsThe data will supplement findings from the Phase 2 study of baricitinib in combination with remdesivir, conducted as part of the Adaptive COVID-19 Treatment Trial (ACTT-2) by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the U.S. National Institutes of Health (NIH). This study enrolled its first patient last month and will evaluate the efficacy and safety of 4 mg baricitinib once daily in combination with remdesivir versus remdesivir alone.

Patrik Jonsson, Senior Vice President and President of Eli Lilly and Company, stated: “Eli Lilly“Committed to combating this global pandemic, this includes testing whether existing drugs, including baricitinib, can help treat COVID-19 complications in patients. This randomized controlled study is an important step in our understanding of baricitinib as a potential treatment for COVID-19.”

Vincent C. Marconi, M.D., Professor of Medicine and Global Health at Emory University School of Medicine and the Emory Rollins School of Public Health, stated, “Following the successful treatment of moderate to severe COVID-19 with remdesivir, hospitalized patients still require new approaches to reduce mortality. Several ongoing studies on baricitinib will provide the necessary data on combination therapy that leverages antiviral activity alongside suppression of the cytokine storm.”

Conducting controlled trials to study baricitinib is of great significance for better characterizing its potential benefits and understanding its safety as a treatment for COVID-19. Currently, Eli Lilly is also supporting several investigator-initiated, multicenter and single-center studies in Europe and North America involving patients with COVID-19.Clinical Trials. These studies, conducted by academic and government institutions, will provide treatment data for hundreds of patients receiving baricitinib, placebo, or active control drugs. If the research efforts on baricitinib for the treatment of COVID-19 prove successful,Eli LillyProduction of sufficient supply will continue to support clinical and research use.

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, includingRheumatoid Arthritis(RA), psoriasis,DiabetesRenal disease, atopic dermatitis, systemicLupus Erythematosusetc.

There are four JAK enzymes: JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines are involved in various inflammatory andAutoimmunityThe pathogenesis of sexual diseases suggests that JAK inhibitors may be widely used to treat various inflammatory diseases. In kinase assay tests, 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 co-develop Olumiant and certain follow-on compounds. To date, Olumiant has been approved in 70 countries worldwide (including the United States, the European Union, and Japan) as monotherapy or in combination with methotrexate for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).Rheumatoid ArthritisTreatment of adult patients with rheumatoid arthritis (RA). In clinical studies, Oluminant demonstrated significant improvement in the signs and symptoms of RA compared to standard-of-care therapies (e.g., methotrexate monotherapy or adalimumab combined with background methotrexate therapy).

BesidesEli Lilly, in April this year, Novartis announced a collaboration with Incyte to launch a Phase IIIClinical Trials(RUXCOVID), evaluating the JAK1/2 inhibitor ruxolitinib (Jakafi/Jakavi) in combination with standard of care (SoC) for the treatment of COVID-19-associated cytokine storm. In this collaborative study, Incyte will sponsor the U.S. region,NovartisSponsor the conduct of trials outside the United States.

Ruxolitinib is a first-in-class oral JAK1/JAK2 inhibitor. Hyperactivated signaling via the JAK-STAT pathway is associated with various cancers and other severe immune-mediated diseases, such as graft-versus-host disease (GVHD). Given that many patients with severe respiratory complications caused by COVID-19, such as pneumonia, exhibit features consistent with cytokine storm and enhanced JAK-STAT pathway activation, it is hypothesized that ruxolitinib may play a therapeutic role in these patients. (Bioon.com)

Original Source: Lilly Begins a Phase 3 Clinical Trial with Baricitinib for Hospitalized COVID-19 Patients