Pfizer's JAK1 Inhibitor Abrocitinib Demonstrates Superiority Over Approved Therapy in Phase 3 Trial for Atopic Dermatitis

On August 30, 2021, Pfizer announced that the Phase 3 clinical trial JADE DARE of the investigational oral JAK1 inhibitor abrocitinib met its co-primary and key secondary efficacy endpoints. The trial results showed that, compared with the active comparator, abrocitinib demonstrated statistical superiority across all evaluated efficacy endpoints, with a safety profile consistent with previous studies.

Abrocitinib is an oral JAK1 inhibitor. JAK1 inhibition is believed to modulate multiple cytokines involved in the pathophysiology of atopic dermatitis, including interleukins IL-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP). On October 28, 2020, Pfizer announced that the FDA had accepted the New Drug Application for abrocitinib for the treatment of moderate-to-severe atopic dermatitis in patients aged 12 years and older, and granted it Priority Review designation. Previously, the drug had also been granted Breakthrough Therapy designation by the FDA.

This 26-week, randomized, double-blind, double-dummy, active-controlled, multicenter JADE DARE trial is designed to compare the efficacy and safety of abrocitinib with an approved IL-4Rα antibody therapy in patients with atopic dermatitis. The co-primary efficacy endpoints are the proportion of patients achieving at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS; score range: 0–10) at Week 2, and the proportion of patients achieving a ≥90% improvement from baseline in the Eczema Area and Severity Index (EASI) (EASI-90) at Week 4. The key secondary endpoint is the proportion of patients achieving EASI-90 at Week 16.

▲Molecular structure of abrocitinib (Image source: Edgar181, Public domain, via Wikimedia Commons)

Regarding safety, the percentage of patients experiencing adverse events was higher in the abrocitinib group than in the active control group. The proportion of patients experiencing serious adverse events, severe adverse events, and adverse events leading to study discontinuation was similar between the two treatment groups. Two deaths occurred in patients treated with abrocitinib, but investigators considered them unrelated to the investigational drug. No cases of malignancy or venous thromboembolism (VTE) were reported. The safety profile of abrocitinib observed in the trial was consistent with previous studies.

Atopic dermatitis is a chronic skin disease characterized by cutaneous inflammation and skin barrier dysfunction, with clinical manifestations including erythematous/violaceous patches, pruritus, induration/papules, and exudation/crusting. It is also one of the most common chronic, relapsing pediatric skin diseases, affecting approximately 10% of adults and 20% of children worldwide. Many patients with moderate-to-severe disease experience inadequate symptom control and require additional therapeutic options to alleviate their symptoms.

The full results of JADE DARE will be submitted for presentation at upcoming scientific conferences and published in medical journals. Additionally, Pfizer plans to share these data with the U.S. FDA and other regulatory authorities worldwide reviewing regulatory submissions for abrocitinib.

References:

[1] Positive Top-Line Results From Pfizer’S Phase 3 Jade Dare Trial Comparing The Efficacy Of Abrocitinib And Dupilumab For Moderate To Severe Atopic Dermatitis. Retrieved August 30, 2021, from https://www.pfizer.com/news/press-release/press-release-detail/positive-top-line-results-pfizers-phase-3-jade-dare-trial

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