Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ:INCY) announced today that the U.S. Food and Drug Administration (FDA) has approved OLUMIANT® (baricitinib), a once-daily pill, as a first-in-disease systemic treatment for adults with severe alopecia areata (AA), available as 4-mg, 2-mg and 1-mg tablets.
The recommended dose is OLUMIANT 2-mg/day, with an increase to 4-mg/day if treatment response is inadequate.
For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4-mg/day.
Once an adequate response is achieved on 4-mg/day, the dosage is to be decreased to 2-mg/day.
OLUMIANT is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.
The approval was based on Lilly’s BRAVE-AA1 and BRAVE-AA2 trials, the largest Phase 3 AA clinical trial program completed to date, evaluating the efficacy and safety of OLUMIANT in 1,200 adult patients with severe AA (≥50% scalp hair loss as defined by a Severity of Alopecia Tool (SALT) score ≥50)
Across the studies at 36 weeks, 17-22% of patients taking OLUMIANT 2-mg/day and 32-35% of patients taking OLUMIANT 4-mg/day achieved 80% or more scalp hair coverage, compared to 3-5% taking placebo.
Additionally, 11-13% of patients taking OLUMIANT 2-mg/day and 24-26% of patients taking OLUMIANT 4-mg/day achieved 90% or more hair coverage, compared to 1-4% of patients taking placebo; results for OLUMIANT 2-mg/day were not statistically significant under the multiplicity control plan for BRAVE-AA2
Among patients with substantial eyebrow and eyelash hair loss at baseline, improvements in eyebrow and eyelash coverage were seen for patients taking OLUMIANT 4-mg daily at 36 weeks.
The BRAVE-AA clinical program evaluated the safety profile of OLUMIANT.
Few patients discontinued treatment due to adverse events (average of 2.2% across both studies) in the 36-week placebo-controlled period and the majority of treatment-emergent adverse events were mild or moderate in severity
The most commonly reported adverse reactions (≥1%) were upper respiratory tract infections, headache, acne, high cholesterol levels, increases in blood markers related to the muscle, urinary tract infections, elevated liver enzyme levels, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, genital yeast infection, low red blood cell counts, low white blood cell counts, abdominal pain, shingles and weight increase
The U.S. FDA-approved labeling for OLUMIANT includes a boxed warning for risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE) and thrombosis
OLUMIANT is a once-daily, oral JAK inhibitor discovered by Incyte and licensed to Lilly and is available through specialty pharmacies nationwide. Lilly also expects regulatory decisions for OLUMIANT in AA in the European Union and Japan in 2022.
About BRAVE-AA1 and BRAVE-AA2
In these double-blind, placebo-controlled Phase 3 trials, 1,200 patients with severe AA were randomized to receive once-daily OLUMIANT 2-mg, OLUMIANT 4-mg or placebo.
- The primary endpoint was the proportion of patients achieving SALT ≤20 (i.e., 80% or more scalp hair coverage) at Week 36. Across both studies, 17-22% of patients taking OLUMIANT 2-mg/day (BRAVE-AA1=22% [n=40/184]; BRAVE-AA2=17% [n=27/156]) and 32-35% of patients treated with OLUMIANT 4-mg/day (BRAVE-AA1=35% [n=99/281]; BRAVE-AA2=32% [n=76/234]) achieved 80% or more scalp hair coverage, compared to 5% (n=10/189) and 3% (n=4/156) of patients taking placebo in BRAVE-AA1 and BRAVE-AA2, respectively (p≤0.001 for all comparisons to placebo).
- Additionally, 11-13% of patients taking OLUMIANT 2-mg/day (BRAVE-AA1=13% [n=23/184]; BRAVE-AA2=11% [n=17/156]) and 24-26% of patients taking OLUMIANT 4-mg/day (BRAVE-AA1=26% [n=73/281]; BRAVE-AA2=24% [n=55/234]) achieved 90% or more hair coverage, compared to 4% (n=7/189) and 1% (n=1/156) of patients taking placebo in BRAVE-AA1 and BRAVE-AA2, respectively (p<=0.001 for OLUMIANT 4-mg/day comparisons to placebo; p<=0.01 for OLUMIANT 2-mg/day comparison to placebo in BRAVE-AA1). SALT 10 (90% hair coverage) results for OLUMIANT 2-mg/day were not statistically significant under the multiplicity control plan for BRAVE-AA2
Indications and Usage for OLUMIANT (baricitinib) tablets (in the United States)
OLUMIANT is indicated for the treatment of adult patients with severe alopecia areata.
Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.
OLUMIANT is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) blockers.
Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
OLUMIANT is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) tablets
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
SERIOUS INFECTIONS
Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients with rheumatoid arthritis (RA) who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:
- Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Olumiant should not be given to patients with active tuberculosis. Test patients, except those with COVID-19, for latent TB before initiating Olumiant and during therapy. If positive, start treatment for latent infection prior to Olumiant use.
- Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
- Bacterial, viral, and other infections due to opportunistic pathogens.
Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
The most common serious infections reported with Olumiant included pneumonia, herpes zoster, and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients: with chronic or recurrent infection; who have been exposed to TB; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.
The risks and benefits of treatment with Olumiant in COVID-19 patients with other concurrent infections should be considered.
Consider anti-TB therapy prior to initiation of Olumiant in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves. The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.
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