October 18, 2021

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COVID-19: FDA expands JAK inhibitor Olumiant (Barictinib) EUA!

COVID-19: FDA expands JAK inhibitor Olumiant (Barictinib) EUA!

COVID-19: FDA expands JAK inhibitor Olumiant (Barictinib) EUA!

 

COVID-19: FDA expands JAK inhibitor Olumiant (Barictinib) EUA!  FDA expands Incyte/Eli Lilly JAK inhibitor Olumiant (Barictinib) emergency use authorization (EUA)!

 

COVID-19: FDA expands JAK inhibitor Olumiant (Barictinib) EUA!

 

Compared with placebo + standard care, Olumiant + standard care reduced the risk of death by 39%.

 

Recently, Eli Lilly and its partner Incyte jointly announced that the U.S. Food and Drug Administration (FDA) has expanded the oral JAK inhibitor Olumiant (Generic name: baricitinib, Barictinib) ) Emergency use authorization (EUA), allowing treatment with or without remdesivir, while EUA was previously limited to the combination with remdesivir.

In November 2020, the U.S. FDA granted Olumiant EUA: Combine Olumiant with Veklury (remdesivir, remdesivir) for suspected or laboratory-confirmed new coronavirus pneumonia (COVID-19), requiring oxygen supplementation/non-invasive or noninvasive Invasive mechanical ventilation/extracorporeal membrane oxygenation (ECMO), hospitalized adults and pediatric patients aged ≥2 years. The EUA recommended dose is: Olumiant 4 mg once a day for 14 days or until discharge.

Ilya Yuffa, senior vice president and president of Eli Lilly Biopharmaceuticals, said: “The combined use of baricitinib and remdesivir has provided a treatment option for many patients. Under the current authorized use, it can help prevent certain COVID-19 hospitalized patients. Progress to ventilation or death, and speed up recovery. Today’s FDA action provides doctors with additional treatment options to continue to meet the urgent medical needs brought about by this pandemic. Based on increasing evidence, we are Baricitinib is confident about its potential as an important treatment option for COVID-19 hospitalized patients who need supplemental oxygen.”

The FDA expanded the Olumiant EUA based on data from the Phase 3 COV-BARRIER (NCT04421027) study for the treatment of hospitalized COVID-19 patients. The results of the study were announced in April this year. The data showed that by day 28, although the study did not meet the primary endpoint, compared with placebo + standard care (SoC, including corticosteroids and remdesivir), Olumiant + standard care will The risk of death was reduced by 39% (p=0.0018).

Olumiant’s active pharmaceutical ingredient is baricitinib, which is a selective and reversible JAK1 and JAK2 inhibitor that is taken orally once a day. It is currently in clinical development for the treatment of a variety of inflammatory diseases and autoimmune diseases, including Rheumatoid arthritis (RA), psoriasis, diabetic nephropathy, atopic dermatitis, systemic lupus erythematosus, etc. There are 4 types of JAK enzymes, namely JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines are involved in the pathogenesis of various inflammations and autoimmune diseases, suggesting that JAK inhibitors may be widely used in the treatment of various inflammatory diseases. In the kinase detection test, baricitinib showed 100 times stronger inhibition against JAK1 and JAK2 than JAK3.

Eli Lilly and Incyte reached an exclusive cooperation agreement in 2009 to jointly develop Olumiant and some subsequent compounds. So far, Olumiant has been approved by more than 70 countries (including the United States, the European Union and Japan) for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA). In November 2020, Olumiant received EU approval for a new indication for use in adult patients with moderate to severe atopic dermatitis suitable for systemic treatment.

COV-BARRIER is a randomized, double-blind, placebo-controlled study that evaluated the efficacy of oral JAK inhibitor Olumiant (once a day, 4 mg) combined with standard of care (SoC) in the treatment of hospitalized COVID-19 patients. SoC may include corticosteroids, antimalarial drugs, antiviral drugs, and/or azithromycin. The study was launched in June 2020 and enrolled 1,525 hospitalized patients who did not require supplemental oxygen (habit score [OS] is 4), needed supplemental oxygen (OS 5) or high flow oxygen/non-invasive ventilation (OS 6). These patients also need to have an increase in at least one inflammatory marker, which is an indicator of the risk of disease progression. According to local clinical practice, all patients received SoC treatment, of which 79% received corticosteroids (91% of which received dexamethasone), 19% received remdesivir at baseline, and some patients received both treatments at the same time . In the study, patients were randomized to receive a 4 mg oral dose of Olumiant or placebo once a day at a ratio of 1:1 for 14 days or until discharge.

The results showed that the study did not reach statistical significance in terms of the composite primary endpoint. The composite primary endpoint was defined as: by day 28, the proportion of patients who progressed to receiving first non-invasive ventilation (including high-flow oxygen) or invasive mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) or died. Compared with the placebo+SoC treatment group (30.5%), the Olumiant+SoC treatment group (27.8%) has a 2.7% less likely to progress to ventilation (non-invasive or mechanical) or death. This difference is not statistically significant (ratio Ratio [OR]=0.85; 95%CI: 0.67-1.08; p=0.180).

However, a pre-specified key secondary endpoint showed that by day 28, Olumiant+SoC significantly reduced the risk of death by 39% compared with placebo+SoC (nominal p=0.0018; Olumiant group: 62/764[ 8.1%], placebo group: 101/761[13.3%]; hazard ratio [HR]=0.56; 95%CI: 0.41, 0.77). A numerical reduction in mortality was observed in all baseline severity subgroups of patients treated with Olumiant, and it was most significant in patients who received noninvasive mechanical ventilation at baseline (the mortality rate in the Olumiant+SoC group was 17.5%, and the mortality rate in the placebo+ The mortality rate in the SoC group was 29.4%; hazard ratio [HR]=0.52; 95% CI: 0.33, 0.80; nominal p value = 0.0065). There was also a reduction in mortality among pre-specified subgroups of patients with or without corticosteroid treatment at baseline.

In the study, the incidence of adverse events and serious adverse events was similar in the Olumiant group (44.5% and 14.7%, respectively) and the placebo group (44.4% and 18.0%, respectively). The incidence of severe infection and venous thromboembolism (VTE) was 8.5% and 2.7% in the Olumiant group, and 9.8% and 2.5% in the placebo group, respectively. No new safety signals that may be related to the use of Olumiant have been discovered.

Professor E. Wesley Ely, a co-investigator of the COV-BARRIER study and co-director of the Critical Illness Brain Dysfunction and Survival (CIBS) Center at Vanderbilt University Medical Center, said: “Recent clinical data help us better understand The potential role of baricitinib in the treatment of certain COVID-19 hospitalized patients, and the expansion of the EUA represents a key step in the fight against this epidemic and will save the lives of hospitalized COVID-19 patients.”

 

(source:internet, reference only)


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