June 03, 2020: “Pfizer Inc. announced that JAMA Dermatology has published complete results from the second Phase 3 monotherapy pivotal study (JADE MONO-2) of abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, in patients aged 12 and older with moderate to severe atopic dermatitis (AD).
Consistent with the first Phase 3 monotherapy study (JADE MONO-1), both doses of abrocitinib met all co-primary and key secondary endpoints and were generally well tolerated.
“Results from the second pivotal trial for abrocitinib reinforce the potential symptom relief it can offer those living with moderate to severe atopic dermatitis, including for itch — one of the most bothersome symptoms of AD,” said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development.
“We are hopeful that these findings, should abrocitinib be approved, will translate into meaningful improvements for patients who face daily challenges with this disease.”
JADE MONO-2 Trial Design
JADE MONO-2 was a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of two doses (100mg and 200mg once daily) of abrocitinib monotherapy over 12 weeks.
A total of 391 subjects with moderate to severe atopic dermatitis were randomized to abrocitinib 200mg, abrocitinib 100mg, and placebo in the trial.
Efficacy endpoints evaluated measures of improvements in skin clearance, disease extent and severity, and itch. The co-primary study endpoints in JADE MONO-2 were the proportion of patients who achieved:
- an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin and two-point or greater improvement relative to baseline at Week 12.
- at least a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI) score at Week 12.
The key secondary endpoint was the proportion of patients achieving a four-point or larger reduction in itch severity measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) at Weeks 2, 4, and 12.
The proportion of patients who achieved a 90% or greater change from baseline in EASI score at Week 12 was included as a secondary endpoint.
JADE MONO-2 Study Efficacy Results
Abrocitinib
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 substantial 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.
Atopic Dermatitis
AD is a chronic skin disease characterized by inflammation of the skin and skin barrier defects.
Lesions of AD are characterized by erythema (redness), itching, induration (hardening)/papulation (formulation of papules), and oozing/crusting.
AD is one of the most common, chronic, relapsing childhood dermatoses, affecting up to 10% of adults and up to 20% of children worldwide.”
