Olumiant (Baricitinib) Description
Olumiant (Baricitinib) is a Janus kinase inhibitor (JAK) that blocks a specific family of enzymes, interfering with the pathway leading to inflammation. Its active substance, baricitinib, blocks the action of enzymes called Janus kinases that play an essential role in immune processes that lead to inflammation.
JAKs are intracellular enzymes that transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function, says the U.S. FDA.
Olumiant is an immunosuppressant (a medicine that reduces the activity of the immune system). Olumiant is a once-daily, oral JAK inhibitor approved in the U.S. and more than 70 countries to treat moderate to severe rheumatoid arthritis (RA) adults. Olumiant was first authorized in the EU and Japan in 2017 to treat RA and adult patients with moderate to severe atopic dermatitis candidates for systemic therapy.
OLUMIANT's Long-Term Safety Profile was established up to 9.3 years in Integrated Analysis of More Than 3,700 Rheumatoid Arthritis patients in November 2021. Detailed and additional results were published in the Annals of the Rheumatic Diseases.
The U.S. FDA-approved labeling for Olumiant includes a Boxed Warning for Serious Infections, Malignancy, and Thrombosis. On July 28, 2021, the FDA updated the EUA. NDC CODE: 0002-4182. For information on the authorized use of baricitinib and mandatory requirements under the EUA, please review the FDA Letter of Authorization (Dec. 2021), Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers. ChemSpider ID26373084; Molecular Formula C16H17N7O2S; ChEMBL: CHEMBL2105759
Eli Lilly and Company (LLY) is a global health care leader based in Indianapolis, IN, that unites caring with discovery to create medicines that make life better for people worldwide.
Incyte (INCY) is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development, and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com.
Olumiant (Baricitinib) Effectiveness Against COVID-19
The WHO strongly recommends baricitinib for patients with severe or critical COVID-19. The WHO recommends that it be given with corticosteroids. On January 14, 2022, the WHO issued a strong recommendation for baricitinib for patients with severe or critical COVID-19. It is part of a class of drugs called Janus kinase (JAK) inhibitors that suppress the overstimulation of the immune system. The WHO recommends that it be given with corticosteroids. This is the eighth update of the WHO's living guidelines on therapeutics and COVID-19, based on evidence from seven trials involving over 4,000 patients with non-severe, severe, and critical COVID-19. And baricitinib has been invited for WHO Prequalification, which assesses the quality, efficacy, and safety of priority health products to increase access in lower-income countries.
The Lancet Respiratory Medicine published a new study on September 1, 2021, that concluded by saying, 'Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard-of-care alone and was associated with reduced mortality in hospitalized adults with COVID-19.' A related Commentary published by The Lancet stated 'Compared with placebo, patients who received baricitinib had a 38·2% relative reduction and five percentage points absolute reduction in 28-day all-cause mortality (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), with a number needed to treat to prevent one additional death of 20. No other anti-COVID-19 therapy has shown such a profound reduction in mortality.'
On April 29, 2021, the EMA started evaluating the use of Olumiant in hospitalized COVID-19 patients requiring supplemental oxygen. And Japan issued authorization on April 23, 2021.
Olumiant (Baricitinib) Indication
Olumiant is a U.S. FDA-approved to treat moderately to severely active rheumatoid arthritis. OLUMIANT® (baricitinib) 2-mg is indicated for treating adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.
On November 19, 2020, the FDA issued an emergency use authorization to use baricitinib, in combination with remdesivir (Veklury), for the treatment of suspected or laboratory-confirmed COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.
Olumiant (Baricitinib) Availability
Baricitinib is Approved and commercially available as OLUMIANT in the U.S. and more than 70 countries as a treatment for adults with moderate to severe rheumatoid arthritis and in the European Union and Japan for the treatment of adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy.
Olumiant (Baricitinib) Safety Information
The following provides essential safety information on the unapproved use of baricitinib under the Emergency Use Authorization. Use in Specific Populations: Pregnancy: Baricitinib should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus; Renal Impairment: There are limited data for baricitinib in patients with severe renal impairment. Therefore, Baricitinib is not recommended for patients on dialysis, have end-stage renal disease, or have acute kidney injury; Hepatic Impairment: Baricitinib has not been studied in patients with severe hepatic impairment. Therefore, Baricitinib should only be used in patients with severe hepatic impairment if the potential benefit outweighs the potential risk.
Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine.
Olumiant (Baricitinib) Adverse Reactions
Most common adverse reactions include: upper respiratory tract infections (16.3%, 11.7%), nausea (2.7%, 1.6%), herpes simplex (0.8%, 0.7%) and herpes zoster (1.0%, 0.4%) for Olumiant 2 mg and placebo, respectively.
Patients treated with Olumiant are at risk of developing serious infections that lead to hospitalization or death. Most patients who developed these infections took concomitant immunosuppressants such as methotrexate or corticosteroids. Thrombosis, including DVT and PE, has been observed at an increased incidence in Olumiant-treated patients compared to placebo. Also, arterial thrombosis events in the extremities have been reported in clinical studies with Olumiant.
Olumiant (Baricitinib) Delivery
Baricitinib (Olumiant) is a prescription oral tablet. The recommended dose for this EUA is baricitinib 4-mg once daily for 14 days or until hospital discharge. OLUMIANT (baricitinib) 1 mg (NDC 0002-4732-30); OLUMIANT (baricitinib) 2 mg (NDC 0002-4182-30).
Avoid the use of live vaccines with baricitinib.
Olumiant (Baricitinib) News
January 14, 2022 - The BMJ News reported: WHO recommends baricitinib and sotrovimab to treat patients.
January 14, 2022 - The WHO strongly recommended baricitinib for patients with severe or critical COVID-19 and recommends that it be given with corticosteroids.
September 1, 2021 - Vanderbilt University Medical Center published a statement: Hospitalized patients with COVID-19 who received the rheumatoid arthritis drug baricitinib, in combination with the standard of care including corticosteroids, died less often than those receiving only the standard of care, according to a study released this week in The Lancet Respiratory Medicine.
August 3, 2021 - Eli Lilly and Company and Incyte announced results from an additional cohort of 101 adult patients from the COV-BARRIER trial. In this sub-study, patients with COVID-19 on mechanical ventilation or extracorporeal membrane oxygenation (ECMO) who received baricitinib plus standard of care were 46% less likely to die by Day 28 compared to patients who received placebo plus standard of care (nominal p-value=0.0296; hazard ratio [HR] [95% CI] = 0.54 [0.31, 0.96]; analysis not adjusted for multiplicity). The cumulative proportion of patients who died by Day 28 was 39.2 percent (n/N: 20/51) in the baricitinib arm versus 58 percent in the placebo arm (n/N: 29/50). Similar mortality benefit was observed by Day 60 (HR [96% CI] = 0.56 [0.33, 0.97]) with a cumulative proportion of death of 45.1 percent (n/N: 23/51) for baricitinib compared to 62.0 percent for placebo (n/N: 31/50). These findings are consistent with the reduction in mortality observed in the overall COV-BARRIER patient population.
July 29, 2021 - Eli Lilly and Company and Incyte announced the U.S. FDA had broadened the Emergency Use Authorization (EUA) for baricitinib to allow for treatment with or without remdesivir. In contrast, the EUA was previously restricted to use only in combination with remdesivir. The EUA now provides for the use of baricitinib to treat COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
July 16, 2021 - Eli Lilly and Company and Incyte announced that the U.S. FDA would not meet the Prescription Drug User Fee Act action date for the supplemental new drug application for baricitinib for treating adults with moderate to severe atopic dermatitis. The delay is related to the FDA's ongoing assessment of JAK inhibitors.
May 10, 2021 - Eli Lilly informed Reuters it had signed licensing agreements with Cipla Ltd, Lupin Ltd, and Sun Pharma to expand the availability of baricitinib in India for treating COVID-19 patients. Baricitinib has been given restricted emergency use by India's Central Drugs Standard Control Organisation combined with remdesivir (Veklury) to treat hospitalized COVID-19 adult patients requiring supplemental oxygen.
April 30, 2021 - Through new analyses of BREEZE-AD5 Phase 3 clinical trial data and an extended safety analysis across multiple trials, Eli Lilly and Company and Incyte's Olumiant® (baricitinib) 2-mg tablet taken once daily showed improvement in key measured treatment outcomes compared to placebo, and helped further characterize the long-term safety profile in adults with moderate- to severe atopic dermatitis.
April 29, 2021 - The European Medicines Agency announced it has started evaluating an application to extend Olumiant (baricitinib) use to include treatment of COVID-19 in hospitalized patients from 10 years of age who require supplemental oxygen.
April 20, 2021 - Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ: INCY) announced results from a second Phase 3 trial (BRAVE-AA1) evaluating the efficacy and safety of once-daily baricitinib 2-mg and 4-mg in adults with severe alopecia areata (AA). The data are consistent with findings from the first Phase 3 clinical trial, BRAVE-AA2, top-lined earlier this year. In both investigational trials, a statistically significant proportion of patients treated with baricitinib achieved the primary endpoint of hair regrowth across the two dosing regimens at Week 36 compared to patients treated with placebo. AA is an autoimmune disease that currently has no therapies approved by the U.S. Food and Drug Administration.
April 8, 2021 - Eli Lilly and Company and Incyte announced results of COV-BARRIER, 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, defined as a difference in the proportion of participants progressing to the first noninvasive 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 (noninvasive 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).
March 3, 2021 - Eli Lilly and Company and Incyte announced top-line results from BRAVE-AA2, a Phase 3 study evaluating the efficacy and safety of once-daily baricitinib 2-mg and 4-mg in adults with severe alopecia areata (AA). Both doses of baricitinib met the primary efficacy endpoint at Week 36, demonstrating a statistically significant improvement in scalp hair regrowth than those randomized to placebo. AA is an autoimmune disease that causes patchy hair loss on the scalp, face, and sometimes on other body areas that can progress. Baricitinib has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) to treat AA. This classification aims to expedite the development and review of drugs intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over already available therapies on a clinically significant endpoint(s). There are currently no FDA-approved treatments for AA.
November 19, 2020 - Coronavirus (COVID-19) Update: FDA Authorizes Drug Combination for Treatment of COVID-19.
Olumiant (Baricitinib) Clinical Trials
Olumiant is active in many clinical trials for various indications, including COVID-19, Alopecia, and Rheumatoid Arthritis.
Dec. 9, 2021 - Efficacy and safety of baricitinib for treating hospitalized adults with COVID-19 (COV-BARRIER): a randomized, double-blind, parallel-group, placebo-controlled phase 3 trial. Interpretation: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone and was associated with reduced mortality in hospitalized adults with COVID-19.
April 8, 2021 - Eli Lilly and Company and Incyte announced today the results of COV-BARRIER, 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, defined as a difference in the proportion of participants progressing to the first occurrence of noninvasive 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 (noninvasive 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).
May 2020 - results from 1,033 patients. Patients who received baricitinib in combination with remdesivir had a shorter median recovery time than patients who received remdesivir alone. In ACTT-2, there was a significant reduction in the proportion of patients progressing to noninvasive ventilation, invasive mechanical ventilation or death, in the baricitinib plus remdesivir group compared to remdesivir. A numerical decrease in mortality risk through Day 29 was observed in patients treated with baricitinib plus remdesivir compared to remdesivir.