Drug Update · Dermatology

FDA Approves difamilast for Mild‑Moderate AD: 38% IGA Success in Trial 2

July 24, 2026

FDA approval date

2026-02-12

Indication

Topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis

Primary endpoint (Trial 2)

IGA success 38% with ADQUEY vs 13% with vehicle at Week 4

Approved formulation/dose

Ointment 1%; apply thin layer twice daily

Clinical Perspective

This approval affects dermatologists, pediatricians, primary care clinicians, and other prescribers who treat adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis, as ADQUEY is FDA-labeled for these populations ^[1]^[3]. The source-confirmed trial results support topical use of difamilast twice daily with IGA success rates of 38% versus 13% in Trial 2 and higher response rates versus vehicle in the other pivotal trials ^[3]. How ADQUEY compares directly to other topical PDE-4 inhibitors such as crisaborole in head-to-head efficacy and tolerability in pediatric and adult patients is not reported in the provided source excerpts?

Dr. Divya Agarwal · Dermatology

The FDA approved ADQUEY (difamilast) ointment for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis on 2026-02-12 based on randomized vehicle-controlled trials that showed IGA success of 38% with ADQUEY versus 13% with vehicle in Trial 2 ^[3]^[2]. The approval and labeling reflect results from three multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials ^[3].

Clinical Context

Difamilast (ADQUEY) is a topical phosphodiesterase-4 (PDE-4) inhibitor formulated as a 1% ointment and marketed by Acrotech Biopharma Inc. The product is indicated for adults and pediatric patients 2 years and older with mild to moderate atopic dermatitis ^[1]^[3]. The drug’s mechanism is described as PDE-4 inhibition leading to accumulation of intracellular cyclic AMP and decreased production of various cytokines and chemokines, although the specific mechanism by which difamilast exerts therapeutic action is not well defined in the label ^[1]^[3]. The approval adds an FDA-labeled topical PDE-4 inhibitor option for clinicians treating mild to moderate disease in both pediatric and adult populations ^[2]^[3]. Comparative data against other topical PDE-4 inhibitors or topical nonsteroidal alternatives were not reported in the provided source excerpts.

Key Findings

Trial 2 (Japan) showed ADQUEY achieved IGA success of 70/182 (38%) versus 23/182 (13%) with vehicle at Week 4 (difference 26%; 95% CI 17 to 34) ^[3].
Trial 3 (Japan, pediatric subjects 2–14 years) showed ADQUEY achieved IGA success of 40/85 (47%) versus 15/83 (18%) with vehicle at Week 4 (difference 29%; 95% CI 15 to 42) ^[3].
Trial 1 (multinational: United States, Australia, Poland; subjects ≥10 years) showed ADQUEY achieved IGA success of 9/43 (21%) versus 1/37 (3%) with vehicle at Week 4 (difference 18%; 95% CI 5 to 31) ^[3].
The trials enrolled subjects with Investigator’s Global Assessment (IGA) of 2 (mild) or 3 (moderate) and affected body surface area within the trial-specified ranges; the primary efficacy endpoint for all trials was IGA success (IGA 0 or 1 with ≥2-grade improvement) at Week 4 ^[3].
The approved formulation is a 1% difamilast ointment, for topical use applied twice daily as a thin layer to affected areas ^[1]^[3].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Nasopharyngitis (reported in ≥1% of ADQUEY-treated subjects and more frequently than vehicle) ^[1]^[3].
Application site folliculitis (reported as a less common adverse reaction) ^[1]^[3].
Contact dermatitis (reported as a less common adverse reaction and noted among application-site reactions leading to discontinuation) ^[1]^[3].
Application site rash (reported as a less common adverse reaction) ^[1]^[3].
Molluscum contagiosum (reported as a less common adverse reaction) ^[1]^[3].
Application site pain (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Pruritus at application site (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Vesicles at application site (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Blistering at application site (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Erythema at application site (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Burning at application site (reported among reactions that led to drug discontinuation in open-label trials) ^[1]^[3].
Application site swelling (identified during postmarketing use) ^[1]^[3].

Study Design

The efficacy basis for approval comprised three multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials: Trial 1 (NCT02068352), Trial 2 (NCT03908970), and Trial 3 (NCT03911401). Subjects were randomized 1:1 to ADQUEY 1% ointment or vehicle applied topically to the entire treatment area twice daily; the primary endpoint in all trials was IGA success (IGA 0 or 1 with ≥2-grade improvement) at Week 4 ^[3]. Clinicians should consult current prescribing information for full dosing guidance. The labeling and approval were granted by the U.S. Food and Drug Administration on 2026-02-12, and prescribing information was updated with a label effective date 2026-02-25 ^[3]^[2].

FAQ

Q1 What is ADQUEY (difamilast) approved for?

ADQUEY (difamilast) ointment is approved for the topical treatment of adults and pediatric patients 2 years of age and older with mild to moderate atopic dermatitis. The FDA approval is based on randomized, double-blind, vehicle-controlled trials that enrolled subjects with IGA scores of 2 (mild) or 3 (moderate) and assessed the proportion achieving IGA success at Week 4.

Q2 How does difamilast work?

Difamilast is a phosphodiesterase-4 (PDE-4) inhibitor. Inhibition of PDE-4 leads to accumulation of intracellular cyclic AMP and decreased production of various cytokines and chemokines; the label states the specific mechanism(s) by which difamilast exerts its therapeutic action is not well defined.

Q3 What is the recommended dose of ADQUEY?

ADQUEY ointment 1% is for topical use only. The prescribing information directs applying a thin layer of ADQUEY twice daily to affected areas and rubbing it in completely; wash hands after application and avoid application to infected skin. The product is supplied as a 1% ointment (10 mg of difamilast per gram). Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects?

The most common adverse reaction occurring in ≥1% of subjects treated with ADQUEY and more frequently than vehicle was nasopharyngitis. Less common adverse reactions reported in trials included application site folliculitis, contact dermatitis, application site rash, and molluscum contagiosum. Open-label trials reported application-site reactions (pain, pruritus, vesicles, blistering, erythema, burning, contact dermatitis) that led to discontinuation in some subjects, and postmarketing reports have included application site swelling.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves difamilast for Mild‑Moderate AD: 38% IGA Success in Trial 2

FDA Approves difamilast for Mild‑Moderate AD: 38% IGA Success in Trial 2

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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