Moizerto (difamilast) / Otsuka, Medimetriks, Aurobindo - LARVOL DELTA

Uniform repigmentation following difamilast treatment for vitiligo. (PubMed, Eur J Dermatol) - No abstract available

Journal • Dermatology • Immunology • Vitiligo

The evolving landscape of phosphodiesterase inhibitors in atopic dermatitis management. (PubMed, Expert Opin Pharmacother) - "Approved agents such as crisaborole, roflumilast, and difamilast demonstrate moderate efficacy and favorable safety, mainly in mild-to-moderate AD. Emerging therapies, including apremilast, orismilast, and lotamilast, show variable results and remain under investigation...However, their efficacy is generally lower than that of biologics and JAK inhibitors. Their future role will likely depend on use as adjunctive or personalized therapies rather than replacement of high-efficacy systemic treatments."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pediatrics

Novel nonsteroidal topical therapies for pediatric atopic dermatitis: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Front Immunol) - "Most active regimens improved IGA-TS versus vehicle, except tapinarof 0.5% once daily...Delgocitinib 0.5% twice daily ranked highest for IGA-TS and EASI-75, whereas difamilast 1% twice daily ranked highest for EASI-90...Further head-to-head, long-term, and age-stratified trials are needed. https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420261400624."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics

Emerging topical nonsteroidal therapies in pediatric dermatology: atopic dermatitis, psoriasis, alopecia areata, vitiligo, and seborrheic dermatitis. (PubMed, Curr Opin Pediatr) - "Current pediatric topical therapies are limited for the treatment of AD, psoriasis, AA, vitiligo, and SD. Historically, first line treatment options have included topical corticosteroids (TCS), though these have an increased risk of side effects in a pediatric population. Future clinical practices will likely rely less on TCS and more on NSTT for treatments of chronic pediatric dermatologic conditions."

Journal • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics • Psoriasis • Seborrheic Dermatitis • Vitiligo

Incidence of Skin Infections in Patients with Atopic Dermatitis Treated with Topical Medications: A Cohort Study Using Japanese Claims Data. (PubMed, Dermatol Ther (Heidelb)) - "Difamilast demonstrated a comparable safety profile to other topical treatments regarding skin infections in patients with AD. These findings highlight the importance of monitoring infection risk and ensuring appropriate clinical management when prescribing topical medications for AD."

Journal • Acne Vulgaris • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Genetically Confirmed Localized Perianal Hailey-Hailey Disease Successfully Treated With Topical Difamilast: A Case Report. (PubMed, Cureus) - "Localized perianal Hailey-Hailey disease is an important diagnostic consideration in chronic treatment-resistant perianal erosions. This case highlights the value of careful clinicopathological evaluation and genetic testing in atypical presentations and suggests that topical difamilast may be a useful therapeutic option for localized disease."

Journal • Dermatology • Genetic Disorders • Pain • Pruritus

Difamilast. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Topical difamilast for the treatment of mild-to-moderate atopic dermatitis. (PubMed, Trends Pharmacol Sci) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Efficacy and safety of treatments for atopic dermatitis: a model based meta-analysis of randomized controlled trials. (PubMed, Eur J Clin Pharmacol) - "MBMA was conducted for the time courses of several efficacy index. In conclusion, results showed that there is still a lack of treatment methods that balance efficacy, safety and speed of onset. The results of this MBMA can be used as a reference for optimizing clinical medication and provide a basis for decision-making in the future development of new AD drugs."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Aurobindo Pharma announced that its stepdown subsidiary, Acrotech Biopharma Inc., has received U.S. FDA approval for ADQUEY (difamilast 1%) Ointment. This novel, non-steroidal topical treatment is indicated for the mild-to-moderate atopic dermatitis (eczema) in patients aged 2 and older. (InvestyWise) - "The approval is based on positive results from pivotal Phase III trials demonstrating efficacy against inflammation and pruritus associated with the chronic skin condition."

FDA approval • Atopic Dermatitis

Difamilast Ointment, a Topical PDE4 Inhibitor, for Pediatric Cheilitis Granulomatosa: A Steroid-Sparing Outcome. (PubMed, J Dermatol) - No abstract available

Journal • Pediatrics

A Phase 3, Long-Term, Open-Label Study of Difamilast Ointment to Evaluate Efficacy and Safety in Japanese Infants with Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - P3 | "Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months for up to 52 weeks are effective and well tolerated, indicating a new useful treatment option for this population."

Journal • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease

A Phase 3 Trial of OPA-15406 Foam in Children and Infants With Atopic Dermatitis (clinicaltrials.gov) - P3 | N=198 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

Head-to-Head • New P3 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Targeting Intracellular Pathways in Atopic Dermatitis with Small Molecule Therapeutics. (PubMed, Curr Issues Mol Biol) - "Although biologic agents such as dupilumab, tralokinumab, and lebrikizumab have revolutionized AD management, their high costs, injectable administration, and limited global accessibility highlight the need for alternative options...This review provides a comprehensive analysis of key agents including Janus kinase (JAK) inhibitors (upadacitinib, abrocitinib, baricitinib, ruxolitinib, delgocitinib), phosphodiesterase 4 (PDE4) inhibitors (crisaborole, difamilast, roflumilast, apremilast), as well as STAT6 degraders (KT621, NX3911), aryl hydrocarbon receptor modulators, histamine H4 receptor antagonists (adriforant, izuforant), and sphingosine-1-phosphate receptor modulators (etrasimod, BMS-986166). We summarize their mechanisms of action, pharmacological profiles, and pivotal clinical trial data, emphasizing their potential to address unmet therapeutic needs. Finally, we discuss safety concerns, long-term tolerability, and future directions for integrating small molecule..."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • STAT6

A Phase 3 Trial to Demonstrate the Superiority of 1% OPA-15406 Foam to the Vehicle in Adult Patients With Atopic Dermatitis (clinicaltrials.gov) - P3 | N=156 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

Head-to-Head • New P3 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Restoration of Skin Barrier Function by Difamilast in Tmem79-/- Mice with Spontaneous Dermatitis (ESDR 2025) - "In mice topically treated with 1% difamilast, compared to the vehicle group, TEWL recovered around day 5, followed by a significant improvement in severity score from around day 14. These results provide in vivo evidence suggesting that the restoration of skin barrier function may precede the anti-inflammatory action of difamilast."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Difamilast induces human beta defensin 3 production via CREB and NRF2 in human keratinocytes. (PubMed, J Dermatol Sci) - No abstract available

Journal

New topical molecular targeted therapies for atopic dermatitis in children: A systematic review and meta-analysis. (PubMed, Pediatr Allergy Immunol) - "Nine studies (reported in eight articles) involving 2182 patients were included, with 1469 children treated with Janus kinase inhibitors (ruxolitinib and delgocitinib) and phosphodiesterase-4 inhibitors (crisaborole, lotamilast, and difamilast)...New topical targeted therapies administered over 4 weeks are effective and safe for children with atopic dermatitis aged ≤18 years. Further studies are needed to establish their long-term safety and efficacy."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Difamilast topically ameliorates pruritus, dermatitis, and barrier dysfunction in atopic dermatitis model mice by inhibiting phosphodiesterase 4, especially the 4B subtype. (PubMed, J Pharmacol Exp Ther) - "Therefore, we evaluated the effects of difamilast on pruritus, dermatitis, and skin barrier dysfunction in MC903-induced AD model mice. The study also revealed a detailed mechanism of action of difamilast, in which its therapeutic effect is mediated mainly by PDE4B inhibition. This study may provide new insights into the use of difamilast for the treatment of atopic dermatitis."

Journal • Preclinical • Asthma • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • Psoriasis • Pulmonary Disease • Respiratory Diseases

Effectiveness and safety of topical phosphodiesterase 4 inhibitors in children with mild-to-moderate atopic dermatitis: A systematic review and meta-analysis. (PubMed, J Int Med Res) - "Currently, crisaborole appears to be the optimal choice for balancing safety and efficacy. As research in this area is still in its early stages, further high-quality trials are essential for establishing standards of clinical care.INPLASY registration number: INPLASY202520121."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

To Demonstrate the Superiority of IMP (0.3% and 1% OPA-15406 Ointment) Versus the Vehicle in Pediatric Patients with AD (clinicaltrials.gov) - P3 | N=240 | Completed | Sponsor: Otsuka Beijing Research Institute | Recruiting ➔ Completed | Trial completion date: May 2025 ➔ Jan 2025 | Trial primary completion date: Nov 2024 ➔ Jul 2024

Head-to-Head • Trial completion • Trial completion date • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics

Systematic Literature Review and Network Meta-Analysis of Clinical Efficacy and Safety of Topical Treatments for Patients with Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - "This study establishes the efficacy and safety of current topical treatment options and recently marketed delgocitinib and difamilast ointments for AD in Japan."

Journal • Retrospective data • Review • Acne Vulgaris • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

DIFENSE Study Protocol: Early Intervention With Difamilast Ointment in Infantile Early-Onset Atopic Dermatitis for Prevention of Transcutaneous Sensitisation. (PubMed, Clin Exp Allergy) - No abstract available

Journal • Allergy • Atopic Dermatitis • Dermatitis • Dermatology • Food Hypersensitivity • Immunology

To Demonstrate the Superiority of IMP (1% OPA-15406 Ointment) to the Vehicle in Adult Patients with AD (clinicaltrials.gov) - P3 | N=270 | Completed | Sponsor: Otsuka Beijing Research Institute | Recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Executive summary: Japanese guidelines for atopic dermatitis (ADGL) 2024. (PubMed, Allergol Int) - "To achieve this, topical anti-inflammatory drugs such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In the revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus