Frequently Asked Questions:
- What is difamilast?
Difamilast (Adquey) is a nonsteroidal, selective topical PDE4 inhibitor. It is FDA approved as a 1% ointment for mild to moderate atopic dermatitis in patients aged 2 years and older.
- How quickly does difamilast work?
Across the phase 2 and 3 trials, difamilast 1% produced significant improvements in EASI scores and itch within the first week of twice-daily use.
- Does difamilast cause gastrointestinal side effects?
No clinically meaningful gastrointestinal safety signals, including diarrhea, were observed across the clinical program.
Difamilast 1% ointment (Adquey) improved disease severity and itch within 1 week in adults and children with mild to moderate atopic dermatitis across phase 2 and 3 trials. The pooled program data were presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, Nevada.¹ No clinically meaningful gastrointestinal safety signals emerged in any study.
The US Food and Drug Administration (FDA) approved difamilast, a nonsteroidal, selective topical phosphodiesterase 4 (PDE4) inhibitor, in February 2026 for patients aged 2 years and older with mild to moderate atopic dermatitis.² The poster consolidates findings from the clinical program supporting twice-daily application.¹ It was presented by Joshua Zeichner, MD, of the Icahn School of Medicine at Mount Sinai, and Lisa Swanson, MD, of Ada West Dermatology and St. Luke’s Children’s Hospital.
How Was Difamilast Evaluated Across the Clinical Program?
The program included 3 randomized, vehicle-controlled trials of twice-daily ointment.¹ In the phase 2 analysis, 121 individuals aged 10 - 70 years were given difamilast 1% treatment (n = 43), difamilast 0.3% (n = 41), or vehicle (n = 37) for a total of 8 weeks.
The first phase 3 trial randomized 365 subjects aged 15 - 70 years to difamilast 1% (n = 183) or vehicle (n = 182) for 4 weeks.¹ The second phase 3 trial enrolled 251 children aged 2 - 14 years, who received difamilast 1% (n = 85), difamilast 0.3% (n = 83) or vehicle (n = 83) for a total of 4 weeks.
Investigator’s Global Assessment (IGA) success, defined as a score of 0 or 1 with an improvement of at least 2-grades, was determined to be a key efficacy end point. The studies were also designed to assess Eczema Area and Severity Index (EASI) responses among subjects, itch, and patient-reported outcomes (PROs).¹
What Efficacy Did Difamilast Show in Adults and Children?
In the phase 3 trial of adolescents and adults, 38.46% of those applying difamilast 1% saw IGA success at the 4-week mark, compared with 12.64% applying vehicle (P < .0001).¹ Mean EASI improvement was 32.6% vs 10.4% at week 1 and 49.1% vs 10.5% at week 4 (both P < .0001). Itch scores also improved significantly at both time points.
