The FDA ( U.S. Food and Drug Administration ) 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, must be considered 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 BRAVE-AA1 and BRAVE-AA2 trials, the largest phase 3 Alopecia Areata clinical trial program completed to date, evaluating the efficacy and safety of Olumiant in 1,200 adult patients with severe alopecia areata ( greater than or equal to 50% scalp hair loss as defined by SALT ( Severity of Alopecia Tool ) score greater than or equal to 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 have 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 have 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 has 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% or more ) 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.
BRAVE-AA1 and BRAVE-AA2
In these double-blind, placebo-controlled phase 3 trials, 1,200 patients with severe alopecia areata were randomized to receive once-daily Olumiant 2-mg, Olumiant 4-mg or placebo.
The primary endpoint was the proportion of patients achieving SALT less than or equal to 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 less than or equal to 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 less than or equal to 0.001 for Olumiant 4-mg/day comparisons to placebo; p less than or equal to 0.01 for Olumiant 2-mg/day comparison to placebo in BRAVE-AA1 ). ( Xagena )
Source: Eli Lilly, 2022