Pfizer Abrocitinib hits mark in phase 3 of Atopic Dermatitis trial

New York: Pfizer Inc. has announced positive top-line results from the Phase 3 JADE TEEN study of abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, in patients 12 to <18 years of age with moderate to severe atopic dermatitis (AD) who were also on background topical therapy. Both doses of abrocitinib met the co-primary endpoints and were generally well tolerated.

Abrocitinib is an oral small molecule that selectively inhibits Janus kinase (JAK) 1. Inhibition of JAK1 is thought to modulate multiple cytokines involved in pathophysiology of atopic dermatitis, including interleukin (IL)-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP).

Abrocitinib received Breakthrough Therapy designation from the FDA for the treatment of patients with moderate to severe AD in February 2018. Breakthrough Therapy designation was initiated as part of the Food and Drug Administration Safety and Innovation Act (FDASIA) signed in 2012. As defined by the FDA, a breakthrough therapy is a drug intended to be used alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If a drug is designated as a Breakthrough Therapy, the FDA will expedite the development and review of such drug.

"Up to twenty percent of children are affected by atopic dermatitis and there remains a significant unmet need for new treatment options that may improve their care," said Michael Corbo, Ph.D., Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development. "For children and adolescents, these findings build on the positive results of our companion Phase 3 monotherapy trials that included patients twelve years and older."

Results showed that the percentage of patients achieving each co-primary efficacy endpoint at Week 12 was statistically significantly higher with both doses of abrocitinib than with placebo.

As a key secondary endpoint, the percentage of patients who had a clinically significant reduction in itch by Weeks 2, 4, and 12 of treatment was statistically significantly higher at each time point for the 200mg abrocitinib dose, and at Week 2 for the 100mg abrocitinib dose, compared to placebo. As the 100mg dose did not achieve a significant difference at Week 4, despite having achieved it at Week 2, no further testing for key secondary endpoints were performed. As such, improvement in the other key secondary endpoint, Pruritus, and Symptoms Assessment for Atopic Dermatitis (PSAAD), cannot be inferred. The PSAAD is a patient-reported measurement scale developed by Pfizer.

The safety profile seen with abrocitinib was consistent with previous studies. Safety results showed that a higher percentage of patients receiving either the 100mg or 200mg dose of abrocitinib experienced adverse events compared to placebo (56.8%, 62.8%, and 52.1%, respectively). The percentage of patients who experienced serious adverse events or adverse events leading to study discontinuation were similar across the placebo (2.1% each), abrocitinib 100mg (0% and 1.1%, respectively), and abrocitinib 200mg (1.1% and 2.1%, respectively) treatment arms.

The co-primary endpoints in the study were the proportion of patients who achieved an Investigator's Global Assessment (IGA) of clear (0) or almost clear (1) and a two-point or greater reduction from baseline at Week 12, and the proportion of patients who achieved at least a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI) score at Week 12.

The key secondary endpoints were the proportion of patients achieving a four-point or larger reduction in itch severity from baseline measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) at Weeks 2, 4, and 12; and the magnitude of decrease in the PSAAD score at Week 12.

JADE TEEN is the fourth trial in the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program. Pfizer recently announced complete results from the second trial in the program, JADE MONO-2. Full results from JADE TEEN will be submitted for presentation at a future scientific meeting and publication in a medical journal.

JADE TEEN was a randomized, double-blind, placebo-controlled, parallel-group study. A total of 285 subjects 12 to <18 years of age with moderate to severe atopic dermatitis were randomized to receive once-daily abrocitinib 200mg, abrocitinib 100mg, or placebo for 12 weeks while also on background topical therapy.

Eligible subjects completing the 12-week treatment period of the study had the option to enter a long-term extension (LTE) study, B7451015. Subjects discontinuing early from treatment, or who were otherwise ineligible for the LTE study, entered a 4-week follow up period in this study.

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