Pfizer's JAK1 Inhibitor Abrocitinib Achieves Dual Primary Endpoints in Second Pivotal Monotherapy Phase 3 Trial for Atopic Dermatitis

Compiled by newborn

Pfizer Recently Announced Complete Results from the Second Pivotal Monotherapy Phase III Study (JADE MONO-2) of Oral JAK1 Inhibitor Abrocitinib for Atopic Dermatitis (AD). The study was conducted in patients aged 12 years and older with moderate-to-severe AD, and the data were consistent with those from the first monotherapy Phase III study (JADE MONO-1): all co-primary endpoints and key secondary endpoints were met. Compared with placebo, both doses of abrocitinib demonstrated statistically significant superiority in improving skin clearance, eczema area and severity, and pruritus.

JADE MONO-2 is a randomized, double-blind, placebo-controlled Phase III study designed to evaluate the efficacy and safety of abrocitinib monotherapy over 12 weeks. In this study, a total of 391 patients with moderate-to-severe atopic dermatitis (AD) were randomly assigned to receive once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo. The efficacy endpoints included improvements in skin clearance, disease area and severity, and pruritus.

The co-primary endpoints of the study were the proportion of patients who achieved the following: an Investigator’s Global Assessment (IGA) score of clear (IGA score of 0) or almost clear (IGA score of 1), with an improvement of ≥2 points from baseline, and a ≥75% improvement in the Eczema Area and Severity Index (EASI) score from baseline at Week 12 of treatment. The key secondary endpoint was the proportion of patients with a reduction in itch severity of ≥4 points from baseline, as measured by the Peak Pruritus Numerical Rating Scale (PP-NRS), at Weeks 2, 4, and 12 of treatment. The proportion of patients achieving a ≥90% reduction in EASI score from baseline (EASI-90) at Week 12 of treatment was listed as a secondary endpoint of the study.

Efficacy Results from the JADE MONO-2 Study:

By Week 12, a higher proportion of patients treated with abrocitinib achieved IGA (0/1), EASI-75, PP-NRS, and EASI-90 responses compared with those in the placebo group. The results for the co-primary and secondary efficacy endpoints are summarized in the table below:

From Week 2 to Week 12, the proportion of patients achieving IGA, EASI-75, PP-NRS, and EASI-90 responses with abrocitinib treatment was higher than that with placebo at each time point, with the earliest response observed at Week 2.

Safety Results from the JADE MONO-2 Study:

The most frequently reported treatment-emergent adverse events (TEAEs) in the study were nausea, nasopharyngitis, and atopic dermatitis. Other safety outcomes are summarized in the table below:

Serious treatment-related adverse events observed in the study were reported in 2 patients in the 100 mg treatment group (herpangina and pneumonia) and 1 patient in the placebo group (eczema herpeticum and staphylococcal infection); no serious treatment-related adverse events were reported in the 200 mg treatment group.

One patient with concurrent cardiovascular risk factors died of unknown cause three weeks after receiving the last 100-mg dose of abrocitinib; the investigator considered this unrelated to the study drug.

In the study, the most common adverse events leading to discontinuation were headache in the 200 mg treatment group and atopic dermatitis in the 100 mg treatment group and the placebo group.

Atopic dermatitis is a chronic skin disease characterized by skin inflammation and impaired skin barrier function. Its lesions are marked by erythema (redness and swelling), pruritus, induration/papules, and exudation/crusting. It is one of the most common chronic, relapsing skin diseases, affecting 10% of adults and 20% of children worldwide.

JADE MONO-2 is the second trial in the JAK1 Atopic Dermatitis Efficacy and Safety Global Development Program (JADE). Recently, Pfizer announced positive topline results from JADE COMPARE, the third trial in this program. Additional data from other studies within the JADE program will be available later this year.

In the United States, the FDA granted abrocitinib Breakthrough Therapy designation for the treatment of patients with moderate-to-severe AD in February 2018. Pfizer plans to submit a New Drug Application (NDA) to the FDA for abrocitinib in the treatment of AD later this year.

Reference Source: Complete Results from Second Pivotal Monotherapy Study of Abrocitinib Published in JAMA Dermatology