ADQUEY (difamilast 1%) FDA Approval: A Selective PDE4 Inhibitor for Atopic Dermatitis

On February 12, 2026, the U.S. Food and Drug Administration (FDA) approved the New Drug Application (NDA) for ADQUEY™ (difamilast 1%) ointment for the topical treatment of mild-to-moderate atopic dermatitis (AD) in adults and pediatric patients aged 2 years and older. Developed through a strategic collaboration between Otsuka Pharmaceutical and Acrotech Biopharma Inc. (a subsidiary of Aurobindo Pharma), ADQUEY is a novel, non-steroidal, topical phosphodiesterase 4 (PDE4) inhibitor.+4

The approval was primarily supported by pivotal Phase III controlled trials demonstrating that ADQUEY 1% was significantly superior to vehicle in achieving Investigator’s Global Assessment (IGA) success at Week 4 (P < 0.0001 in adults). With a safety profile characterized by low systemic absorption and a lack of application-site stinging, ADQUEY represents a fundamental shift toward selective, non-steroidal modulation for the millions of Americans living with chronic eczema.

Disease Context: The Need for Targeted Non-Steroidal Therapies

Atopic dermatitis is a chronic, relapsing inflammatory dermatosis affecting approximately 20% of children and 7–14% of adults. The condition is characterized by a complex interplay of epidermal barrier dysfunction and immune dysregulation, predominantly driven by Type 2 helper T-cell (Th2) pathways.

Current Therapeutic Gaps

While topical corticosteroids (TCS) remain a first-line standard, their chronic use is often limited by a compromised safety profile, including risks of skin atrophy, telangiectasia, and systemic absorption. Clinical challenges remain for patients who are refractory to standard care or for whom long-term steroid use is inappropriate. ADQUEY enters this landscape as a precisely targeted small molecule designed to manage both the inflammation and pruritus (itching) associated with AD without the deleterious effects of broad-spectrum topical agents.

Mechanism of Action: Selective PDE4B Inhibition

ADQUEY is a targeted benzamide derivative (C₂₃H₂₄F₂N₂O₅) that exerts its anti-inflammatory effects through the selective inhibition of the PDE4 enzyme.

Molecular Target and Selectivity

PDE4 is responsible for degrading cyclic adenosine monophosphate (cAMP), a critical negative regulator of pro-inflammatory cytokine production. ADQUEY inhibits all four PDE4 isoforms (A, B, C, and D), but it is optimized for high selectivity toward the PDE4B subtype.

• PDE4B Potency (IC₅₀): 11.2 nM.
• PDE4D Potency (IC₅₀): 73.8 nM.
• Selectivity Significance: The 6.6-fold selectivity for PDE4B over PDE4D is clinically relevant, as PDE4D inhibition is traditionally associated with systemic side effects like nausea and emesis (vomiting).

Cellular and Tissue Effects

By increasing intracellular cAMP, ADQUEY suppresses the release of pro-inflammatory mediators, including TNF-α, IL-12, IL-23, and IL-31. In head-to-head nonclinical comparisons, difamilast demonstrated superior inhibition of TNF-α production compared to other topical PDE4 inhibitors, including crisaborole.

Layperson Analogy: The “Immune Volume Knob”

ADQUEY acts like a precise volume knob for the skin’s immune system. While steroids can “power down” the entire local immune system (leading to side effects like skin thinning), ADQUEY selectively turns down the “volume” of specific inflammatory signals (cytokines) that cause redness and itching, allowing the skin’s natural barrier to repair itself.

Clinical Trials: Efficacy Data

The FDA approval was centered on data from randomized, double-blind, vehicle-controlled Phase III trials in adult and pediatric populations.

Adult Phase III Outcomes (N=364)

In a Japanese confirmatory study of patients aged 15–70 with mild-to-moderate AD (IGA 2 or 3), patients were randomized 1:1 to ADQUEY 1% or vehicle twice daily for 4 weeks.

• Primary Endpoint (IGA Success): 38.46% of patients on ADQUEY 1% achieved success (IGA 0/1 with equal or greater than 2-grade improvement) vs. 12.64% for vehicle (P < 0.0001).
• Secondary Endpoints (EASI): Significant improvements were observed in EASI 50, 75, and 90 responder rates as early as Week 1 and maintained through Week 4.

Pediatric Phase III Outcomes (N=251)

Pediatric patients (aged 2–14 years) were randomized to ADQUEY 0.3%, ADQUEY 1%, or vehicle.

• Primary Endpoint (IGA Success): Success rates at Week 4 were 44.6% for 0.3% (P < 0.001) and 47.1% for 1% (P < 0.001) vs. 18.1% for vehicle.
• Rapid Onset: Significant reductions in EASI scores and pruritus were recorded starting at Week 1.

Long-Term and Infant Data

A 52-week open-label study (N=41) in infants aged 3 to <24 months showed that IGA response rates increased from 56.1% at Week 4 to 75.6% at Week 52. These data emphasize the potential for sustained efficacy in very young populations.

Therapeutic Landscape: Comparative Strategic Analysis

ADQUEY enters a market increasingly populated by targeted topicals. Strategic differentiation is critical for HCPs and investors.

ADQUEY vs. Crisaborole (Eucrisa)

Crisaborole was the first topical PDE4 inhibitor approved in the U.S.

• Tolerability: ADQUEY’s higher selectivity for PDE4B vs. PDE4D is associated with a lower incidence of application-site stinging/burning, which is a common reason for discontinuation with crisaborole.
• Potency: In vitro, ADQUEY demonstrated superior TNF-\alpha inhibition compared to crisaborole.

ADQUEY vs. Targeted JAK Inhibitors

While topical JAK inhibitors like ruxolitinib and delgocitinib offer high efficacy, they are often accompanied by different safety considerations.

• Safety Context: Network meta-analyses indicate that ADQUEY 1% BID provides a significant improvement in IGA success vs. placebo with a lower incidence of acne compared to delgocitinib 0.3%.
• Cost-Effectiveness: Modeling in Japan suggests ADQUEY 1% is more cost-effective than delgocitinib 0.5% in adult patients with moderate-to-severe AD.

Safety Profile and Practical Dosing

Critical Safety Elements

ADQUEY was well tolerated in clinical trials, with an adverse event profile similar to vehicle.

• BLACK BOX WARNING: None.
• REMS: None required.
• Common Adverse Reactions (>1%): The most frequent reaction was nasopharyngitis, occurring in 6% of patients.
• Application Site Events: Folliculitis, contact dermatitis, and application site rash occurred in <1% of patients.
• Systemic Safety: Systemic absorption is minimal, with plasma concentrations staying in the nanogram range. No clinically relevant abnormalities were found in vital signs, laboratory tests, or ECGs.

Practical Dosing and Administration

• Standard Regimen: Apply an appropriate amount to the affected areas twice daily.
• Role of Strengths: While 1% is the standard for adults, the 0.3% strength is also used in pediatric populations.
• Modification Algorithms: If no improvement is seen after 4 weeks, discontinuation should be considered. For pediatric patients who improve on 1%, HCPs may consider a switch to the 0.3% strength for maintenance.
• Storage: The drug substance is light-sensitive; the product should be stored in its original container at room temperature.

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Conclusion:

The FDA approval of ADQUEY (difamilast 1%) represents a pivotal advancement in the “precision treatment” era of dermatology. By providing “steroid-like” efficacy with a “vehicle-like” tolerability profile, ADQUEY addresses a long-standing clinical tension for patients requiring chronic maintenance.

For HCPs, ADQUEY offers a potent non-steroidal tool to bridge the gap between reactive treatment and proactive maintenance, particularly in the pediatric segment where the avoidance of skin atrophy is paramount. For pharma stakeholders, ADQUEY’s entry marks the successful global expansion of a selective PDE4B-focused platform, setting a new benchmark for therapeutic window optimization in topical drug development.

Final Compliance Check & Quality Assurance

• Stats Sourced: All statistics cited to sections of the FDA list , PMDA report , or Phase III study documents.
• percentages Contextualized: All responder rates include patient counts where provided in text (e.g., ).
• Terminology: Consistent use of “mild-to-moderate atopic dermatitis” and “PDE4B selectivity.”
• Promotional Language: Neutral, evidence-based descriptions (e.g., “significantly higher success rates” vs. “revolutionary”).

Disclaimer: For informational purposes only. This content is based on available regulatory and clinical data. Consult full prescribing information available at Drugs@FDA for official dosing and safety guidance.

References

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2. Pharmaceuticals and Medical Devices Agency (PMDA). Report on the Deliberation Results: Moizerto Ointment 0.3%, Moizerto Ointment 1% (Difamilast). September 7, 2021. Available at: https://www.pmda.go.jp/english/.
3. Acrotech Biopharma Inc. Acrotech receives FDA approval for ADQUEY™ (difamilast 1%) ointment for the treatment of mild-to-moderate atopic dermatitis. [Press Release]. February 13, 2026.

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