U.S. FDA Approves AbbVie’s Oral JAK1 Inhibitor RINVOQ® for Refractory Moderate to Severe Atopic Dermatitis in Adults and Adolescents

News on January 14, 2022 /BioValleyBIOON/ -- AbbVie recently announced that the U.S. Food and Drug Administration (FDA) has approved Rinvoq (upadacitinib), for the treatment of:Patients aged ≥12 years with refractory moderate to severe atopic dermatitis (AD)The drug is specifically indicated for: adult and pediatric patients (≥12 years) with moderate to severe AD who have not responded to prior treatments, whose condition is not well controlled with other oral medications or injectables (including biologics), or for whom the use of other oral medications or injectables is not recommended. Regarding dosage, Rinvoq 15mg once daily can be used in adults and children aged 12 years and older weighing ≥40 kg. In adults under 65 years and children who have not achieved an adequate response, the dose may be increased to 30mg once daily.

In the European Union, Rinvoq was approved in August 2021 for the treatment of adult and pediatric (≥12 years) patients with moderate to severe AD who are candidates for systemic therapy. In terms of dosage, the recommended dose of Rinvoq for adult patients is 15mg or 30mg once daily; for adolescents (12-17 years) and elderly patients aged 65 years and older, the recommended dose is 15mg once daily. Rinvoq can be used with or without topical corticosteroids (TCS).

Rinvoq is an oral, once-daily, selective, reversible JAK inhibitor that has been approved for four indications in the EU (Rheumatoid Arthritis[RA], psoriatic arthritis [PsA], ankylosing spondylitis [AS], atopic dermatitis [AD]), with three indications approved in the United States (RA, PsA).Rinvoq 15mg is indicated for the treatment of all the above-mentioned conditions, while Rinvoq 30mg is only indicated for the treatment of AD.

This approval of the AD indication is supported by data from one of the largest Phase 3 global registration programs for AD. The program includes three pivotal global studies (Measure Up 1, Measure Up 2, AD Up), enrolling more than 2,500 patients with moderate to severe atopic dermatitis (AD). These studies evaluated the efficacy and safety of Rinvoq as monotherapy (Measure Up 1, Measure Up 2) and in combination with topical corticosteroids (AD Up) compared to placebo. In all three studies, the co-primary endpoints were: at least a 75% improvement in the Eczema Area and Severity Index (EASI75) and a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear skin) at week 16 of treatment.

The results showed,In all Phase 3 studies, both doses of Rinvoq achieved all primary and secondary endpoints: compared with the placebo group, patients in the Rinvoq treatment group showed rapid and significant improvements in skin clearance and itching at week 16 and other time points (p<0.001).

Specific efficacy data: (1) A higher proportion of patients achieved EASI 75 at Week 16: Rinvoq 15mg group (MU1:70%; MU2:60%; AU:65%), Rinvoq 30mg group (MU1:80%; MU2:73%; AU:77%), placebo group (MU1:16%; MU2:13%; AU:26%). (2) A higher proportion of patients achieved vIGA AD 0/1 at Week 16: Rinvoq 15mg group (MU1:48%; MU2:39%; AU:40%), Rinvoq 30mg group (MU1:62%; MU2:52%; AU:59%), placebo group (MU1:8%; MU2:5%; AU:11%). (3) A higher proportion of patients achieved clinically meaningful pruritus reduction (≥4-point improvement in Worst Pruritus NRS) at Week 16: Rinvoq 15mg group (MU1:52%; MU2:42%; AU:52%) and Rinvoq 30mg group (MU1:60%; MU2:60%; AU:64%), placebo group (MU1:12%; MU2:9%; AU:15%). (4) Compared with the placebo group, clinically meaningful pruritus reduction (≥4-point improvement in Worst Pruritus NRS) and skin clearance (EASI 75) were observed as early as Week 1 and Week 2, respectively, in both Rinvoq dose groups. (5) Results at Week 16 for patients receiving either dose of Rinvoq were maintained up to Week 52.

In terms of safety, the most commonly reported adverse reactions (≥5%) in the Rinvoq 15mg and 30mg groups were upper respiratory tract infections (25.4%), acne (15.1%), herpes simplex (8.4%), headache (6.3%), and increased blood creatine phosphokinase (CPK, 5.5%). The most common serious...Adverse ReactionsIs severe infection (<1.0%).

Atopic Dermatitis (AD) is a common, chronic, recurrent, inflammatory skin disease, characterized by a repeated cycle of itching and scratching, leading to cracked, scaly, and oozing skin. It is estimated that up to 25% of children and 10% of adults will be affected by AD at some point in their lives. Around 20%-46% of adult AD patients suffer from moderate to severe disease. The symptoms significantly impose substantial physical, psychological, and economic burdens on patients.

The active pharmaceutical ingredient in Rinvoq is upadacitinib, an oral, selective, and reversible JAK1 inhibitor discovered and developed by AbbVie. It is being developed to treat several immune-mediated inflammatory diseases. JAK1 is a kinase that plays a key role in the pathophysiological processes of various inflammatory diseases.

Currently, Rinvoq treatsRheumatoid Arthritis(RA), Atopic Dermatitis (AD), Psoriatic Arthritis (PsA), Axial Spondyloarthritis (axSpA), Crohn's Disease (CD), Ulcerative Colitis (UC), Giant Cell Arteritis (GCA), and Large Vessel Vasculitis Phase 3Clinical TrialIn progress.

AbbVie has high expectations for Rinvoq. At the recently held J.P. Morgan Healthcare Conference (JPM), AbbVie reaffirmed2 ProductsImmunologyNewcomer (Rinvoq and IL-23 inhibitor Skyrizi)The heavy-weight guidelines are expected to impact these two drugsThe combined sales in 2025 are expected to reach $15 billion, offsetting the sales loss of the flagship product Humira (adalimumab) due to biosimilar competition in the U.S. market in 2023.

Humira is the world's first approved anti-TumorTumor Necrosis Factor-α (TNF-α) drugs achieved global sales of $20.39 billion in 2020, ranking as the world's top-selling drug for nine consecutive years. In the European Union, multiple adalimumab biosimilars have already been marketed. Meanwhile, in the U.S. market, Humira will face biosimilar competition in 2023. (Bioon.com)

Source of the original text:U.S. FDA Approves RINVOQ® (upadacitinib) to Treat Adults and Children 12 Years and Older with Refractory, Moderate to Severe Atopic Dermatitis