Pfizer recently announced the complete results of the second key single-agent phase III study (JADE MONO-2) of the oral JAK1 inhibitor abrocitinib in the treatment of atopic dermatitis (AD). The study was conducted in patients with moderate-to-severe AD who were 12 years of age and older. The data was consistent with the first single-agent phase III study (JADE MONO-1): the study reached all common primary endpoints and key secondary endpoints. Compared with placebo, both doses of abrocitinib showed statistically significant advantages in improving skin lesion clearance, eczema area and severity, and itching.
JADE MONO-2 is a randomized, double-blind, placebo-controlled phase III study designed to evaluate the efficacy and safety of abrocitinib monotherapy for 12 weeks. In the study, a total of 391 patients with moderate to severe AD were randomly assigned to abrocitinib 200 mg, 100 mg, and placebo once daily. The end point of curative effect is the improvement of skin lesion clearance, disease area and severity, and itching.
The study’s common primary endpoint was the proportion of patients who achieved the following goals: At the 12th week of treatment, the investigator’s overall assessment (IGA) was complete removal of the lesion (IGA score of 0) or almost complete clearance (IGA score of 1) and relative baseline improvement ≥ 2 points, the area and severity index (EASI) score of eczema at the 12th week of treatment improved ≥75% from the baseline. The key secondary endpoint was the proportion of patients with a reduction in the severity of pruritus measured by the Peak-Pitch Itching Rating Scale (PP-NRS) by ≥4 points from baseline at weeks 2, 4, and 12 of treatment. The proportion of patients whose EASI score decreased by ≥90% from baseline (EASI-90) at week 12 was included as a secondary endpoint of the study.
The results of the JADE MONO-2 study:
By week 12, patients receiving abrocitinib had a higher proportion of IGA (O/1), EASI-75, PP-NRS, and EASI-90 responses than patients in the placebo group. The secondary endpoint results are as follows:
From week 2 to week 12, abrocitinib treatment achieved a higher proportion of patients with IGA, EASI-75, PP-NRS, and EASI-90 responses at each time point than placebo, and the response appeared as early as week 2.
The safety results of the JADE MONO-2 study:
The most frequently reported treatment-emergent adverse events (TEAE) in the study were nausea, nasopharyngitis, and atopic dermatitis. Other safety results are shown in the following table:
The serious adverse events observed in the study that were considered to be treatment-related were reported by 2 patients in the 100 mg treatment group (herpetic angina and pneumonia) and by 1 patient in the placebo group (herpes eczema and staphylococcal infection) In the 200 mg treatment group, there were no serious treatment-related adverse events.
A patient who also had cardiovascular risk factors died of an unknown cause three weeks after taking the last dose of 100 mg abrocitinib. Investigators believe that this has nothing to do with the study drug.
In the study, the most common adverse events leading to drug withdrawal were headache in the 200 mg treatment group and atopic dermatitis in the 100 mg treatment group and placebo group.
Atopic dermatitis is a chronic skin disease characterized by skin inflammation and skin barrier defects. The lesions are characterized by erythema (redness), itching, induration/pimples, and exudation/scabs. It is the most common, chronic, One of recurrent 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 Project (JADE). Recently, Pfizer announced the positive top-line results of the third trial of the project, JADE COMPARE. Additional data from other studies in the JADE project will be obtained later this year.
In the United States, the FDA granted abrocitinib a breakthrough drug qualification for the treatment of patients with moderate to severe AD in February 2018. Pfizer plans to submit a new application for abrocitinib for AD to the FDA later this year.