For the second time in four years, AbbVie’s Rinvoq (upadacitinib) has shown superior efficacy to Regeneron and Sanofi’s powerhouse Dupixent (dupilumab) in a head-to-head study in patients with atopic dermatitis (AD).
In the LEVEL UP trial testing patients age 12 and older with moderate-to-severe AD who had an inadequate response to systemic therapy, 20% of those on Rinvoq achieved nearly complete skin clearance with little or no itch after 16 weeks, compared to 9% of those on Dupixent. AbbVie’s anti-inflammatory treatment also conquered Dupixent in all secondary objectives of the phase 3b/4 study.
For the primary endpoint, the standard of comparison was determining the number of patients who achieved a 90% or greater reduction on the Eczema Area and Severity Index (EASI) and attained a 0 or 1 grade on the Worst Pruritis Numerical Rating Scale (WP-NRS). EASI is the primary tool used to determine the severity of AD while WP-NRS measures itch on a 0-10 scale.
“Even while receiving conventional treatments, many patients with atopic dermatitis still continue to live with significant itch and inflammatory skin symptoms that can profoundly impact their everyday lives,” Roopal Thakkar, M.D., AbbVie’s chief medical officer, global therapeutics, said in a release. “Results from this study show that patients with moderate-to-severe atopic dermatitis can strive for both little to no itch and clearer skin.”
Dupixent, which works by inhibiting signaling of both IL-4 and IL-13, was approved to treat AD, its first of five indications, back in 2017. JAK inhibitor Rinvoq meanwhile reached the market in 2019 to treat rheumatoid arthritis. Its approval for AD came in 2022, which is one of seven indications for which it is endorsed. AD is the only disorder for which both are approved. While Dupixent’s label has been expanded to treat AD patients 6 months and older, Rinvoq’s approval is limited to those age 12 and older.
In a 2020 stage 3b trial, Rinvoq conquered Dupixent in AD, with 71% of patients achieving a 75% reduction in EASI compared to 61% for Dupixent after 16 weeks. Rinvoq also came out on top in secondary endpoints, but its edge in the study was overshadowed by the death of one of the patients who was treated with the JAK inhibitor.
In that trial, Rinvoq was provided in a 30 mg dose. In the recent study, patients started with a 15 mg dose which was adjusted up to 30 mg based on clinical response. There were no new safety signals identified in LEVEL UP.
While Rinvoq is a daily oral medication, Dupixent is self-injected, starting with a 600 mg dose for adults, followed by 300 mg doses every two weeks.
“Too many patients are still not achieving optimal disease control in atopic dermatitis despite taking steps to manage their condition,” Jonathan Silverberg, M.D., Ph.D., MPH, professor of dermatology at the George Washington University School of Medicine and Health Sciences, said in the release. “Results from the LEVEL UP study highlight how treatment options such as upadacitinib can achieve high treatment goals in atopic dermatitis.”
With sales of $4 billion in 2023, Rinvoq has combined with Skyrizi, which raked in $7.8 billion last year, to provide AbbVie with a pair of newer immunology drugs that are helping the company compensate for the loss of patient protection for Humira, whose sales peaked at $21.2 billion in 2022.
Dupixent however generated megablockbuster sales of $11.6 billion in 2023 and is on the verge of a potentially lucrative approval to become the first biologic treatment for chronic obstructive pulmonary disease (COPD). Cantor Fitzgerald analyst Josh Schimmer has projected Dupixent’s sales potential at more than $20 billion by the end of this decade as it looks to match the might of Humira's glory days.