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

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

Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology. (PubMed, Pharmaceutics) - "Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology."

Journal • Review • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Dental Disorders • Dermatitis • Dermatology • Dermatopathology • Discoid Lupus Erythematosus • Hidradenitis Suppurativa • Immunology • Inflammation • Inflammatory Arthritis • Lichen Planus • Lupus • Psoriasis • Psoriatic Arthritis • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Rheumatology • Sarcoidosis • Seborrheic Dermatitis • Seronegative Spondyloarthropathies • Stomatitis

English version of clinical practice guidelines for the management of atopic dermatitis 2024. (PubMed, J Dermatol) - "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 these 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."

Clinical guideline • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

Cost-Effectiveness Study of Difamilast 1% for the Treatment of Atopic Dermatitis in Adult Japanese Patients. (PubMed, Dermatol Ther (Heidelb)) - "The results suggest that difamilast 1% is a more cost-effective treatment option compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in adult patients with all-severity AD from a Japanese public health-care perspective."

Cost effectiveness • HEOR • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Impact of Different Mapping Algorithms From Disease-Specific Measures to EQ-5D on Cost-Effectiveness Analysis in Atopic Dermatitis (ISPOR-EU 2024) - "The incremental quality-adjusted life-year (QALY) and ICER for delgocitinib versus difamilast in moderate to severe AD patients were compared using utility directly measured by EQ-5D-5L and mapped utilities from DLQI and pruritus VAS. The choice of different mapping algorithms can substantially impact the ICER and incremental QALY in AD patient evaluation. Therefore, the use of multiple algorithms in CEA should be considered."

Cost effectiveness • HEOR • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Difamilast 1% and Delgocitinib 0.5% in Patients with Moderate-to-Severe Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - "The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Topical anti-inflammatory treatments for eczema: network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "Potent TCS, JAK inhibitors and tacrolimus 0.1% were consistently ranked as amongst the most effective topical anti-inflammatory treatments for eczema and PDE-4 inhibitors as amongst the least effective. Mild TCS and tapinarof 1% were ranked amongst the least effective treatments in three of five efficacy networks. TCI and crisaborole 2% were ranked most likely to cause local application-site reactions and TCS least likely. We found no evidence for increased skin thinning with short-term TCS but an increase with longer-term TCS."

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

A Open-label Study to Assess the Long-term Safety of Difamilast Ointment 1% in Mild to Moderate Atopic Dermatitis (clinicaltrials.gov) - P3 | N=542 | Completed | Sponsor: Acrotech Biopharma Inc. | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Difamilast, a Topical Phosphodiesterase 4 Inhibitor, Produces Soluble ST2 via the AHR-NRF2 Axis in Human Keratinocytes. (PubMed, Int J Mol Sci) - "Additionally, the knockdown of AHR or NRF2 abolished the difamilast-induced sST2 production. These results indicate that difamilast treatment produces sST2 via the AHR-NRF2 axis, contributing to improving AD symptoms by inhibiting IL-33 activity."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • IL13 • IL33 • IL5 • ST2 • TNFA

An Interim Report of a Phase 3, Long-Term, Open-Label Study to Evaluate Efficacy and Safety of Difamilast Ointment 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 is effective and well tolerated as of the interim report in the study period. The final results will be reported in the near future."

Journal • P3 data • P3 data: top line • Atopic Dermatitis • Contact Dermatitis • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease

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 | Recruiting | Sponsor: Otsuka Beijing Research Institute | Trial completion date: Feb 2024 ➔ May 2025 | Trial primary completion date: Dec 2023 ➔ Nov 2024

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

To Demonstrate the Superiority of IMP (1% OPA-15406 Ointment) to the Vehicle in Adult Patients With AD (clinicaltrials.gov) - P3 | N=270 | Recruiting | Sponsor: Otsuka Beijing Research Institute | Trial completion date: Mar 2024 ➔ Jan 2025 | Trial primary completion date: Dec 2023 ➔ Jul 2024

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