Olumiant® (Baricitinib) Description - 2022
Eli Lilly & Co.'s Olumiant® (Baricitinib) is a Janus kinase inhibitor (JAK) that blocks enzymes interfering with the pathway leading to inflammation. Its active substance, baricitinib, blocks the action of enzymes 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. Food and Drug Administration (FDA).
Cytokines are proteins that allow cells to communicate with each other, and excess cytokines may cause inflammation. In RA, joint inflammation may cause pain, swelling, and tenderness. It is not known which disrupted cytokines are most related to the therapeutic effects of Olumiant.
Olumiant is an immunosuppressant 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 who didn't find relief from biologic medicines called tumor necrosis factor blockers. OLUMIANT's Long-Term Safety Profile was established up to 9.3 years in the Integrated Analysis of more than 3,700 RA patients in November 2021, published in the Annals of the Rheumatic Diseases.
ChemSpider ID26373084; Molecular Formula C16H17N7O2S; ChEMBL: CHEMBL2105759; Metabolism: CYP3A4 (<10%); Formula: C16H17N7O2S.
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) Indications
Olumiant is a U.S. FDA-approved treatment for moderately to severely active rheumatoid arthritis. Olumiant is the first immunomodulatory treatment for COVID-19 to receive U.S. FDA approval. Your doctor should do blood tests to check your white and red blood cells before and while you are taking Olumiant.
Olumiant (Baricitinib) For Alopecia Areata
Eli Lilly and Incyte confirmed on May 20, 2022, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for OLUMIANT® (baricitinib) for the treatment of adults with severe alopecia areata (AA).
On March 26, 2022, Eli Lilly announced adults with severe alopecia areata (AA) who took OLUMIANT® (baricitinib) achieved significant scalp, eyelash, and eyebrow hair regrowth and nearly 75% of those who responded to OLUMIANT 4-mg achieved 90% scalp coverage at 52 weeks. The NEJM published an Original investigation of two-phase three clinical trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo concerning hair regrowth at 36 weeks.
In February 2022, the U.S. FDA granted priority review for OLUMIANT in severe AA as a potential first-in-disease medicine. Lilly expects regulatory decisions in the U.S., European Union, and Japan in 2022. The 52-week results showed continued improvement as compared with results after 36 weeks of follow-up, which were reported simultaneously in the New England Journal of Medicine.
Olumiant (Baricitinib) For Atopic Dermatitis
Lilly confirmed on February 3, 2022, that it is in ongoing discussion with the FDA regarding the status of the sNDA for Olumiant for the treatment of adults with moderate-to-severe atopic dermatitis. It is commercially available as OLUMIANT in the EU and Japan for the treatment of severe atopic dermatitis.
On April 7, 2021, an Original Research Article - Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic dermatitis (eczema): An Integrated Analysis from Eight Randomized Clinical Trials - Conclusions: This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. 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 (Baricitinib) For COVID-19
On May 11, 2022, the FDA Approved OLUMIANT (baricitinib), the first and only JAK inhibitor for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation with a recommended dose of 4-mg once daily for 14 days or until hospital discharge, whichever comes first. Baricitinib has been available in the U.S. under EUA since November 2020. For additional information about the authorized use, please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers.
"Nearly one million people with COVID-19 have been treated with OLUMIANT (baricitinib) in approximately 15 countries worldwide," commented Patrik Jonsson, Lilly SVP, president of Lilly Immunology and Lilly USA, and chief customer officer, on May 11, 2022.
The WHO's 9th COVID-19 recommendation issued on March 3, 2022, includes a 'strong recommendation for baricitinib as an alternative immunomodulatory to interleukin-6 (IL-6) receptor blockers, in combination with corticosteroids, in patients with severe or critical COVID-19. When moving from evidence to the strong recommendation to use baricitinib in patients with severe or critical COVID-19, the WHO/GDG emphasized the benefits of survival and decreased length of hospital stay with ease of administration and the likelihood of little or no serious adverse events attributable to the drug. And the choice of whether to use baricitinib or an IL-6 receptor blocker depends on availability, as well as clinical and contextual factors.
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. 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. In December 2021, Guyana started using baricitinib to help treat some hospitalized patients who were experiencing the more severe symptoms of COVID-19. And Japan issued authorization on April 23, 2021.
Olumiant (Baricitinib) Safety Information
Olumiant may cause serious side effects. 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.
The EMA announced on February 11, 2022, that its vaccine committee started a review of the safety of Janus kinase inhibitors used to treat several chronic inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, ulcerative colitis, and atopic dermatitis. The review was prompted by the final results from a clinical trial (study A3921133) of the JAK inhibitor Xeljanz (tofacitinib).
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, who 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. And it is 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. Avoid the use of live vaccines with baricitinib.
It is not known if Olumiant is safe and effective in children.
These are not all the possible side effects of Olumiant. You can report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Olumiant (Baricitinib) Delivery 2022
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).
Eli Lilly's Olumiant (Baricitinib) Revenues
The Company reported for the fourth quarter of 2021, worldwide Olumiant revenue increased 59% compared with the fourth quarter of 2020, to $306.0 million. Increased volume worldwide was partially driven by the utilization of Olumiant for the treatment of hospitalized patients with COVID-19. For the full year of 2021, Olumiant generated worldwide revenue of $1.115 billion, an increase of 75% compared with the full year of 2020. U.S. revenue was $324.1 million, an increase of $260.3 million. Revenue outside of the U.S. increased 38%, to $791.0 million, driven by increased volume and, to a lesser extent, the favorable impact of foreign exchange rates, partially offset by lower realized prices. Increased volume worldwide was partially driven by the utilization of Olumiant for the treatment of hospitalized patients with COVID-19.
Olumiant (Baricitinib) News: 2011 - 2022
May 20, 2022 - Bianca Maria Piraccini, M.D., Ph.D., professor. and head of the Dermatology Unit at the University of Bologna stated, "As there has never been a centrally-authorized therapy for alopecia areata, I'm delighted about Lilly's potential to provide this oral medicine with statistically significant and clinically meaningful Phase 3 clinical trial results for adults with severe alopecia areata across Europe."
May 11, 2022 - Eli Lilly and Company and Incyte announced today the U.S. FDA had approved OLUMIANT® (baricitinib) for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation with a recommended dose of 4-mg once daily for 14 days or until hospital discharge, whichever comes first.
March 26, 2022 - Eli Lilly and Company and Incyte announced a 52-week pooled analysis that demonstrated continued improvement in the scalp, eyebrows, and eyelash hair regrowth from 36-week results published today in the NEJM. Lilly expects regulatory decisions in the U.S., European Union, and Japan in 2022.
March 3, 2022 - The WHO strongly recommends treatment with baricitinib. Because of different mechanisms of action, the GDG considered baricitinib separately from other JAK inhibitors.
March 3, 2022 - The Randomised Evaluation of COVID-19 Therapy phase 2/3 clinical trial results demonstrated that baricitinib reduces the risk of death when given to hospitalized patients with severe COVID-19.
February 3, 2022 - Eli Lilly confirmed ongoing discussion with the U.S. FDA regarding the status of the sNDA for Olumiant® for the treatment of adults with moderate-to-severe atopic dermatitis. At this point, the company does not have alignment with the FDA on the indicated population. Given the Agency's position, there is a possibility that this could lead to a Complete Response Letter.
January 28, 2022 - Eli Lilly and Company and Incyte announced updates on the Phase 3 development program for OLUMIANT® (baricitinib) in adults with active systemic lupus erythematosus (also referred to as SLE and lupus) and the status of the U.S. atopic dermatitis supplemental new drug application. Based on top-line efficacy results from two pivotal Phase 3 trials (SLE-BRAVE-I and II), Lilly has decided to discontinue the Phase 3 development program for OLUMIANT in lupus. Lotus Mallbris, M.D., Ph.D., vice president of global immunology development and medical affairs at Lilly stated: "These decisions do not affect Lilly's other research efforts for OLUMIANT or its approved indications. We are confident in OLUMIANT for approved indications in the U.S. and globally as OLUMIANT has one of the largest and longest sets of available safety data in the JAK inhibitor class, including nine years across the clinical development program."
January 14, 2022 - The BMJ News reported: the 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. 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).
April 7, 2021 - An Original Research Article concluded by stating: This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. Longer exposure to treatment is required to evaluate the risks of malignancies and major adverse cardiovascular events.
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.
February 27, 2011 - Advances in the Medical Treatment of Rheumatoid Arthritis.
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.