Lilly and Incyte Announce Positive Phase 3 Results of JAK Inhibitor Olumiant (Baricitinib) in Alopecia Areata, Demonstrating Up to 80% Scalp Hair Regrowth

Source: PharmaCube Info

Author: Shibei

Recently, Eli Lilly and Incyte jointly announced the detailed results of two pivotal Phase III clinical trials, BRAVE-AA1 and BRAVE-AA2, evaluating the JAK inhibitor Olumiant (baricitinib) for the treatment of alopecia areata. The results demonstrated that patients with severe alopecia areata receiving 4 mg of baricitinib orally once daily achieved significantly greater scalp hair regrowth compared to placebo at Week 24. The companies plan to submit a regulatory application to the US FDA in the second half of this year, positioning baricitinib as a potential first treatment for millions of patients with alopecia areata worldwide.

The BRAVE-AA1 and BRAVE-AA2 studies are the first completed randomized, double-blind, placebo-controlled Phase III trials for the treatment of AA, with 598 and 490 patients completing 36 weeks of treatment, respectively. Both trials enrolled adult patients with severe AA, defined as a SALT score ≥50 (≥50% scalp hair loss). At baseline, the mean SALT score of subjects was 85.5 (85.5% scalp hair loss).

In the BRAVE-AA1 trial, compared with placebo, patients in the baricitinib 4 mg and 2 mg dose groups demonstrated significant improvement in scalp hair regrowth as early as Week 16 and Week 24. At Week 16, compared with placebo (4.2%, n=8), nearly one-fifth (18.5%, n=52) of patients in the baricitinib 4 mg group achieved ≥80% scalp hair coverage (p ≤ 0.001). At Week 24, compared with placebo (4.8%, n=9), one-tenth (11.4%, n=21) of patients in the baricitinib 2 mg group achieved ≥80% scalp hair coverage (p = 0.013).

In the BRAVE-AA2 trial, patients in the baricitinib 4 mg group demonstrated significant improvement in scalp hair regrowth as early as week 24. Compared with placebo (1.3%, n=2), more than one-quarter (28.2%, n=66) of patients achieved ≥80% scalp hair coverage (p ≤ 0.001).

At Week 36 (primary endpoint), the proportion of patients achieving ≥80% scalp hair coverage in the baricitinib 4 mg group was 35.2% and 32.5% in the BRAVE-AA1 and BRAVE-AA2 trials, respectively; in the baricitinib 2 mg group, the proportions were 21.7% and 17.3%, respectively; and for placebo in the two studies, the proportions were 5.3% and 2.6%, respectively.

In both studies, compared with placebo, nearly one-third of patients in the baricitinib 4 mg group achieved complete or near-complete regrowth of eyebrows and eyelashes at Week 36, compared with only 3.1%–5.6% in the placebo group, meeting the study's key secondary endpoint.

The safety profile of baricitinib was consistent with previously reported safety data, with no new safety signals observed. Less than 2.6% of patients discontinued treatment due to adverse events, and most treatment-related adverse events were mild to moderate in severity. The most commonly reported adverse events (≥5%) included upper respiratory tract infection, headache, acne, urinary tract infection, and elevated muscle-related blood markers.

Baricitinib is an oral JAK inhibitor developed by Incyte and licensed to Eli Lilly. It has been approved in over 75 countries worldwide, including the United States, for the treatment of moderate to severe rheumatoid arthritis (RA) in adults. In more than 40 countries, including the European Union and Japan, it has been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Additionally, baricitinib has received marketing authorization in several countries, including Japan and Switzerland, for the treatment of hospitalized patients with COVID-19. Baricitinib is also under development for the treatment of systemic lupus erythematosus in adults and juvenile idiopathic arthritis.

Structural Formula of Baricitinib

Baricitinib tablets were approved in China in June 2019 for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). Eli Lilly has also initiated a Phase III study in China evaluating baricitinib tablets for the treatment of severe and very severe alopecia areata (AA) in adults.

Previously, Hengrui’s JAK1 inhibitor SHR0302 tablets achieved positive results in a Phase II clinical trial for the treatment of alopecia areata. Pfizer’s JAK3 inhibitor PF-06651600 tablets (ritlecitinib) for the alopecia areata indication was granted Breakthrough Therapy designation by the CDE on December 12, with Phase III studies currently underway. Suzhou Zelgen’s JAK1/2/3 inhibitor jacktinib hydrochloride tablets/cream and Concert Pharmaceuticals’ JAK1/2 inhibitor deuterated ruxolitinib are also conducting clinical trials for the treatment of alopecia areata.

Alopecia areata (AA) is a common inflammatory, non-scarring alopecia. Clinically, it presents as sudden-onset, well-demarcated, circular patches of hair loss on the scalp. Most mild cases undergo spontaneous remission, while approximately half of patients experience recurrent episodes that may persist for years or even decades. In a minority of severe cases, hair loss may involve the entire scalp or even all body hair. Clinically, AA can be classified into several subtypes: among them, alopecia totalis refers to the complete loss of all scalp hair, and alopecia universalis refers to the complete loss of all body hair. The exact etiology of AA remains incompletely understood; it is currently considered a hair follicle-specific autoimmune disease resulting from the interplay of genetic and environmental factors. The condition can occur at any age, is most prevalent in young and middle-aged adults, and shows no significant sex difference.