The recently demonstrated superiority of AbbVie’s Rinvoq (upadacitinib) versus Regeneron and Sanofi’s Dupixent (dupilumab) across primary and all secondary endpoints in the Phase IIIb Heads Up study may well showcase its potential to usurp Dupixent as the gold standard of atopic dermatitis (AD) therapy, but it is the speed of which the efficacy became evident in patients that shows the drug’s real promise, says GlobalData, a leading data and analytics company.

Antoine Grey, Senior Immunology Analyst at GlobalData, comments: “While Rinvoq’s results at Week 16 are impressive in themselves – considering they surpassed Dupixent in all efficacy metrics – it is the speed that efficacy became evident in participants treated with Rinvoq that shows real promise. AD patients commonly experience itchiness as a symptom, causing great discomfort and lack of sleep. In the trial, patients saw significant improvements in percentage itch reduction within the first week, and more than twice as many patients treated with Rinvoq experienced at least a 75% improvement in the Eczema Area Severity Index (EASI 75) after just two weeks of therapy (44% Rinvoq vs. 18% Dupixent). However, it remains to be seen whether this efficacy has topped out, or whether Rinvoq’s data will continue with a positive trajectory in more long-term measures.”

However, being a Janus kinase (JAK) inhibitor, Rinvoq may give dermatologists cause for concern.

Grey continues: “With such a strong efficacy profile, Rinvoq has the potential to unseat Dupixent as the gold standard of moderate-to-severe AD therapy but its safety profile may make some dermatologists and patients wary. Although the Heads Up trial didn’t see any instances of venous thromboembolic events (VTEs) – a problem commonly associated with Pfizer’s 10mg Xeljanz (tofacitinib) dose – Rinvoq did have a slightly higher rate of ‘serious adverse events’ (SAEs) and ‘serious infection’ than Dupixent. In fact, the drug has a boxed warning, as it is already approved for rheumatoid arthritis (RA). Another caveat for the drug in AD is that the newly reported data is in the 30mg group, a higher dosage than that approved for RA. Historically, the JAK inhibitors as a class have struggled to show that benefits outweigh risks at the higher more effective dose, displaying solid efficacy but poor safety profiles.”

Dupixent was first approved in 2017 and has had just over three years to establish itself as the premier AD therapy. With its recent approval in pediatric patients, Dupixent is expected to retain the title of safest therapy for moderate-to-severe patients. As a result, GlobalData expects Rinvoq to fall a treatment line behind Dupixent.

Aside from Dupixent, Rinvoq will face another hurdle in the form of Pfizer’s abrocitinib, another JAK inhibitor that is under priority review by the US Food and Drug Administration (FDA).

After the announcement of promising top-line results in November 2020 – and the fact that abrocitinib had been granted Breakthrough Therapy designation earlier in development – Rinvoq’s place as best in class may be in doubt. This is especially as abrocitinib is expected to receive approval in April 2021, before Rinvoq’s anticipated Q2 2021 approval. These factors led GlobalData to forecast 2027 abrocitinib sales of $1.5bn in the 7MM, beating out Rinvoq’s 2027 sales of $1.1bn, which is also attempting to gain approval in AD.

Grey concludes: “Despite Rinvoq not being granted a priority review by the FDA, both Rinvoq and abrocitinib are JAK1-specific inhibitors, which might suggest a similar level of efficacy between the two drugs. However, it is unlikely they will match Dupixent in terms of safety, ensuring Dupixent remains on top of the podium. Considering physician familiarity and its mild side effect profile, GlobalData expects Dupixent to remain on top of the AD market with 2027 sales of $5.3bn in the 7MM.”