Abrocitinib received Breakthrough Therapy designation from the FDA for the treatment of patients with moderate to severe AD in February 2018.

Results from the second pivotal trial for abrocitinib reinforce the potential symptom relief that this Janus kinase 1 (JAK1) inhibitor offers patients living with moderate to severe atopic dermatitis (AD).

Abrocitinib is an investigational oral once-daily JAK1 inhibitor being studied in patients aged 12 and older with moderate to severe AD.  The new findings appear in JAMA Dermatology.

Consistent with the first Phase 3 monotherapy study (JADE MONO-1), both doses of abrocitinib from the second Phase 3 study (JADE MONO-2) met all co-primary and key secondary endpoints and were generally well tolerated.

“We are hopeful that these findings, should abrocitinib be approved, will translate into meaningful improvements for patients who face daily challenges with this disease,” says Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development, in a news release.

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 or 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

By Week 12, a greater proportion of patients on either dose of abrocitinib achieved the IGA, EASI-75, PP-NRS, and EASI-90 responses compared to those on placebo. The following co-primary efficacy and secondary endpoint results were seen at Week 12:

The proportion of patients achieving the IGA, EASI-75, PP-NRS, and EASI-90 responses were higher for abrocitinib treatment at each time point compared with placebo from Week 2 to Week 12, with responses seen as early as Week 2. Similar to JADE MONO 1, significant IGA, EASI-75, and PP-NRS responses were observed from Week 2 through Week 12.

JADE MONO-2 Study Safety Results

The most frequently reported treatment-emergent adverse events were nausea, nasopharyngitis, and AD in the abrocitinib 200mg, abrocitinib 100mg, and placebo groups, respectively.

Observed serious adverse events that were considered related to treatment were reported for two patients in the abrocitinib 100mg group (herpangina and pneumonia) and one patient with two events in the placebo group (eczema herpeticum and staphylococcal infection). There were no serious treatment-related adverse events in the 200mg group.

One patient with co-existing cardiovascular risk factors died from unknown etiology three weeks after receiving the last dose of abrocitinib 100mg once daily, which was deemed unrelated to the study drug by the investigator.

The most frequently reported AEs leading to treatment discontinuation were headache in the abrocitinib 200mg group and atopic dermatitis in the abrocitinib 100mg and the placebo groups.

Additional Details About the JADE MONO-2 Study

Randomization was stratified by baseline disease severity (moderate [IGA=3] and severe [IGA=4] AD) and age (age <18 and ≥18 years). Concomitant use of topical or systemic therapies for AD or rescue medication was not permitted. Patients were permitted to use oral antihistamines and topical non-medicated emollients during the study. 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.

JADE MONO-2 is the second trial in the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program. Pfizer recently announced positive top-line results from the third trial in the program, JADE COMPARE. Additional data from other studies in the JADE program will be available later this year.