ICYMI: Difamilast Ointment Expands Non-Steroidal Options in AD Care

The therapeutic landscape for atopic dermatitis (AD) continues to expand, and the recent US FDA approval of difamilast 1% (Adquey) ointment introduces another non-steroidal option for patients aged 2 years and older with mild to moderate disease. Developed by Otsuka Pharmaceuticals and licensed in the United States to Acrotech Biopharma, difamilast is a topical phosphodiesterase 4 (PDE4) inhibitor designed for twice-daily use.¹

A New Topical PDE4 Inhibitor

Difamilast joins a class of targeted anti-inflammatory therapies that act through inhibition of PDE4, an enzyme involved in the breakdown of cyclic adenosine monophosphate (cAMP). By inhibiting PDE4 activity, intracellular cAMP levels increase, modulating downstream inflammatory cytokine production. PDE4 inhibition has been a validated strategy in inflammatory dermatoses, including AD, where type 2 immune pathways play a central role.

Unlike topical corticosteroids (TCS), which remain first-line for flares but carry well-recognized risks such as skin atrophy and telangiectasia with prolonged use, difamilast offers a non-steroidal alternative. This distinction is particularly relevant in pediatric populations and in sensitive areas such as the face or intertriginous zones, where clinicians and caregivers often express concern about steroid exposure.

Clinical Development in Patients Aged ≥2 Years

The FDA approval was supported by multiple clinical trials, including pivotal phase 3 randomized, vehicle-controlled studies. In these trials, a significantly greater proportion of patients treated with difamilast 1% achieved Investigator’s Global Assessment (IGA) success—defined as clear or almost clear skin with at least a 2-point improvement—after 4 weeks compared with vehicle.²

The safety profile observed across these trials was consistent. The most commonly reported adverse reaction (≥1% and greater than vehicle) was nasopharyngitis. Less common events included application-site folliculitis, contact dermatitis, application-site rash, and molluscum contagiosum. Overall tolerability was comparable across studies, with no new systemic safety signals identified.

For clinicians accustomed to interpreting eczema trials, the 4-week IGA endpoint aligns with regulatory standards seen across other topical approvals. While longer-term comparative data in diverse populations will be informative, the available evidence supports short-term efficacy and acceptable tolerability in the approved age group.

Long-Term and Infant Data from Japan

Although the US approval applies to patients aged 2 years and older, additional context comes from Japanese clinical development programs that evaluated difamilast in younger children, including infants aged 3 to <24 months.

In a 52-week, phase 3, multicenter open-label study conducted in Japan (NCT05372653), 41 infants with mild to moderate AD were treated initially with difamilast 0.3% twice daily, with escalation to 1% permitted based on clinical response. Baseline mean Eczema Area and Severity Index (EASI) was 9.6, and mean affected body surface area (BSA) was 27.1%.

At week 4, 56.1% of infants achieved IGA success. By week 52, this increased to 75.6%. EASI 50, 75, and 90 response rates were 92.7%, 82.9%, and 46.3% at week 4, with maintenance or further improvement through week 52. Notably, among infants who did not initially respond to 0.3%, a majority achieved IGA success after escalation to 1%.

Adverse events were common, reflecting the expected infectious burden in infants; 100% of participants experienced at least one adverse event, most mild or moderate. Frequently reported events included nasopharyngitis, gastroenteritis, and common pediatric viral illnesses. Only one case of folliculitis was considered related to study medication and led to discontinuation. No clinically meaningful laboratory or vital sign abnormalities were observed.

Plasma concentrations were low (mean 7.2 ng/mL for 0.3% and 11.6 ng/mL for 1%), suggesting limited systemic exposure, an important consideration in early childhood.

However, the open-label design, absence of a vehicle control, use of rescue topical corticosteroids in many participants, and the exclusively Japanese study population limit generalizability. Still, these findings provide useful insight into long-term tolerability and sustained response in very young patients.

Positioning in Practice

For clinicians managing AD, the addition of another topical PDE4 inhibitor expands the non-steroidal armamentarium. Treatment goals in mild to moderate disease include achieving and maintaining symptom control while minimizing treatment-related adverse effects and preserving quality of life. Many patients require intermittent or long-term topical therapy; steroid-sparing approaches remain an area of interest.

Difamilast may be considered in patients who have concerns about chronic TCS use, in those with disease involving sensitive areas, or as part of a proactive maintenance strategy. As with other topical therapies, adherence, appropriate quantity of application, and patient education remain critical determinants of real-world effectiveness.

AD remains a chronic, relapsing inflammatory disease with substantial psychosocial impact across the lifespan. The approval of difamilast provides clinicians with an additional non-steroidal option for patients aged 2 years and older, with clinical trial data supporting short-term efficacy and a generally favorable safety profile. Ongoing post-marketing surveillance and real-world data will help clarify its long-term role within evolving treatment algorithms.

References

1. Acrotech Biopharma Inc., announces FDA approval of ADQUEYTM (difamilast 1%) ointment for the treatment of mild-to-moderate atopic dermatitis. News release. Aurobindo. Published February 13, 2026. Accessed February 19, 2026. https://www.aurobindo.com/api/uploads/corporateannouncements/Adquey-(Difamilast)_NDA%20Approval_PressRelease_13-Feb-26.pdf
2. Saeki H, Ohya Y, Baba N, Imamura T, Yokota D, Tsubouchi H. A phase 3, long-term, open-label study of difamilast ointment to evaluate efficacy and safety in Japanese infants with atopic dermatitis. Dermatol Ther (Heidelb). 2026;16(1):339-352. doi:10.1007/s13555-025-01581-1