New drug for atopic dermatitis! Lilly oral JAK inhibitor olumiant single drug treatment of North America phase III clinical research has been successful!

January 30, 2020 / bioun / -- US pharmaceutical giant Eli Lilly and its partner Incyte recently announced that breeze-ad5, a phase III clinical study to evaluate the treatment of moderate to severe atopic dermatitis (AD) adults with oral JAK inhibitor olumiant (barictinib), has reached the primary end point This is a multicenter, double-blind, randomized, placebo-controlled study conducted in North America in adult patients with moderate to severe AD to evaluate the efficacy and safety of single agent treatment with olumiant (two doses: 1mg, 2mg) The primary end point of the study was the proportion of patients who achieved easi75 (an improvement of ≥ 75% in eczema area and severity index [easi] score from baseline) at the 16th week of treatment The results showed that the primary end point was achieved in the 2mg dose of olumiant: at week 16, the proportion of patients who achieved easi75 in the 2mg dose group was significantly higher than that in the placebo group (29.5% vs 8.2%, P ≤ 0.001) In addition, at the 16th week of treatment, compared with the placebo group, a higher proportion of patients in the 2mg dose olumiant treatment group achieved a clear or almost clear ad VI GA score (VI GA score 0 or 1:24.0% vs 5.4%, P ≤ 0.001) In addition, at the 16th week of the treatment, the proportion of patients with 4-point improvement in itch Rating Scale (itch NRS) in the two doses of lumiant treatment group was significantly higher than that in the placebo group (placebo group = 5.7%, 1mg group = 15.9% [P ≤ 0.05], 2mg group = 25.2% [P ≤ 0.001]) The safety in this study is consistent with the safety results previously known by olumiant in AD clinical trials The most common treatment emergent adverse events (teaes) include upper respiratory tract infection, nasopharyngitis and diarrhea No VTE or death was reported in the trial Recently, Lilly published the positive top line results of another phase III clinical study (breeze-ad4) The study was carried out outside the United States The enrolled patients were adults with moderate to severe AD who had insufficient response, intolerance or contraindications to cyclosporine The results showed that the primary end point was reached by 4mg dose of olumiant: at the 16th week of treatment, the proportion of patients with easi75 in 4mg dose of olumiant + TCS group was significantly higher than that in placebo + TCS group (31.5% vs 17.2%, P ≤ 0.05) In addition, at the 16th week of treatment, compared with the placebo + TCS group, a higher proportion of patients in the 4mg dose of lumiant + TCS group achieved a clear or almost clear ad VI GA score (VI GA score 0 or 1:21.7% vs 9.7%, P ≤ 0.05) In addition, at the 16th week of treatment, compared with the placebo + TSC group, the proportion of patients with itch Rating Scale (itch NRS) improved by 4 points was significantly higher in the three doses of lumiant + TSC group (8.2% in the placebo group, 23.1%, 22.9%, 38.2% in the 1mg, 2mg, 4mg doses of lumiant group) Lilly has submitted regulatory applications to the European Drug Administration (EMA) for the treatment of moderate to severe AD with lumiant, and plans to submit regulatory applications in the United States and Japan in 2020 All results from the breeze-ad5 study will be published in future scientific conferences and peer-reviewed journals, and relevant data will continue to support the submission of regulatory application documents of olumiant in the United States "Today's results, together with the positive top line results of phase III clinical trials previously reported, reinforce our commitment to bring the first oral JAK inhibitor to patients with chronic and recurrent skin diseases (i.e., atopic dermatitis) in the United States," said Dr lotus Mallbris, Lilly's vice president of immunology development Atopic dermatitis (AD) is a serious chronic inflammatory skin disease, mainly manifested as severe pruritus, obvious eczema like change and dry skin The disease often occurs in infants and children, and some of the patients last for a lifetime It can seriously affect the quality of life of the patients due to chronic recurrent eczema like rash, severe pruritus, sleep loss, dietary restriction and psychosocial impact The active ingredient of olumiant is baricitinib, which is a selective and reversible inhibitor of Jak1 and JAK2 taken orally once a day It is currently in clinical development and is used in the treatment of a variety of inflammatory and autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, diabetic nephropathy, atopic dermatitis, systemic lupus erythematosus, etc There are four kinds of JAK enzymes, Jak1, JAK2, JAK3 and Tyk2 JAK dependent cytokines participate in the pathogenesis of various inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be widely used in the treatment of various inflammatory diseases In the kinase detection test, barricitinib showed 100 times higher inhibition intensity for Jak1 and JAK2 than JAK3 Lilly and Incyte reached an exclusive cooperation agreement in 2009 to jointly develop the olumiant and some follow-up compounds Up to now, lumiant has been approved by more than 60 countries (including the United States, the European Union and Japan) as a single drug or combination of methotrexate for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults with one or more disease modified antirheumatic drugs (DMARD) with insufficient or intolerable remission In clinical studies, compared with standard nursing therapies (such as methotrexate monotherapy, adalimumab combined with background methotrexate therapy), oluminat significantly improved the symptoms and signs of RA The doses approved by olumiant in the European Union are 4mg and 2mg, and the doses approved in the United States are 2mg In terms of medication, olumiant is taken orally once a day, which can be used as single drug or combined with methotrexate (MTX) or other non biological disease modified anti rheumatic therapy (non biological DMARDs) The combination of olumiant with other JAK inhibitors, or biological DMARD, powerful immunosuppressors such as azathioprine and cyclosporine is not recommended It is worth noting that olumiant's US drug label includes a black box warning that indicates the risk of serious infection, cancer and thrombosis Source: Lily and infinite announcement positive top line results from the North American (breeze-ad5) phase 3 study of oral selective JAK inventor baricinib in patients with moderate to severe atopic dermatis