AbbVie has released the topline results of its Rinvoq (upadacitinib) second pivotal Phase III trial, Measure Up 2, in moderate to severe atopic dermatitis, which tested the Janus kinase (JAK) inhibitor monotherapy against placebo in 810 adolescents and adults at doses of 15mg and 30mg. Similar to the replicate Measure Up 1 study, which had topline results announced in June 2020, both co-primary endpoints of at least a 75% improvement in the Eczema Area Severity Index (EASI 75) from baseline and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at Week 16 were met. Among patients receiving the 15mg and 30mg doses of Rinvoq, 60% and 73%, respectively, achieved EASI 75, whereas only 13% receiving placebo achieved EASI 75. Likewise, 39% of the 15mg group and 52% of the 30mg group met the vIGA-AD threshold, compared to only 5% of the placebo group. Despite such promising efficacy, Rinvoq may struggle to rival Regeneron’s Dupixent (dupilumab), the current gold standard for the treatment of moderate to severe atopic dermatitis, based on the JAK-1 inhibitor’s class-wide boxed warnings for serious infection, malignancy, and thrombosis.
Rinvoq reportedly met all secondary endpoints in the study as well, especially in terms of reducing itch associated with atopic dermatitis. The 15mg and 30mg groups achieved 42% and 60% reductions, respectively, in Worst Pruritus Numerical Rating Scale of four or greater from baseline, compared to 9% in the placebo group. Other notable secondary endpoints that were met include a percentage of patients achieving EASI 75, EASI 90, and EASI 100. Rinvoq had a safety profile consistent with that seen in Measure Up 1, and no new safety risks were observed compared to the safety profile seen in rheumatoid arthritis patients and psoriatic arthritis patients treated with Rinvoq. Fewer serious adverse events were seen in the two treatment groups than in the placebo group, and no venous thromboembolic events were observed in participants treated with Rinvoq.
However, one of the most common AEs was acne, seen in 12.7% and 14.5% of patients receiving 15mg and 30mg Rinvoq, respectively, compared to just 2.2% in the placebo group. Such a significant number of participants developing acne may discourage patients from taking the treatment if it were to be approved, despite being orally administered, unlike Dupixent’s subcutaneous route of administration. Unlike Rinvoq’s boxed warnings, Dupixent has been on the atopic dermatitis market for three years and is well known for its strong safety profile. As such, GlobalData expects the 2027 sales of Rinvoq in the seven major markets (US, France, Germany, Italy, Spain, UK, and Japan) to reach $1.1B and the 2027 sales of Dupixent to reach $5.3B for atopic dermatitis alone.