asivatrep (PAC-14028) / Seoul National University Hospital, Amorepacific - LARVOL DELTA

Attenuation of senile pruritus by PAC-14028-mediated downregulation of the NF-κB and MAPK pathways. (PubMed, Int J Immunopathol Pharmacol) - "By combining the results of multiple assays, we were able to elucidate the molecular mechanism of PAC-14028 to TRPV1. Taken together, the findings indicate that PAC-14028 as a potential therapeutic agent for elderly people with pruritus."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • IL17A

Drug repositioning for rosacea disease: Biological TARGET identification, molecular docking, pharmacophore mapping, and molecular dynamics analysis. (PubMed, Comput Biol Med) - "Furthermore, considering the drugs currently used for rosacea management, we demonstrated stable interactions between isotretinoin and BFH772 with SKAP2, and permethrin and PAC-14028 with S100A7A. Similarly, considering drugs targeting SKAP2 and S100A7A interactome proteins, we found that pitavastatin and dasatinib exert stable interactions with SKAP2, and lovastatin and tirbanibulin with S100A7A...In conclusion, our study provides evidence for the possible contribution of SKAP2 and S100A7A to rosacea pathology. Furthermore, it provides significant information on the molecular interactions between drugs and these proteins, highlighting the importance of considering structural features and binding interactions in the design of targeted therapies for skin disorders such as rosacea."

Journal • Dermatology • Dermatopathology • Rosacea • SKAP2

Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs. (PubMed, Allergy) - "In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti-interleukin-4 receptor (IL-4R) α in 2017), tralokinumab (anti-IL-13 in 2021), lebrikizumab (anti-IL-13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022)...Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan-JAKi), asivatrep (anti-transient receptor potential vanilloid), and phosphodiesterase-4-inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord-blood-derived mesenchymal stem cells, CM310 (anti IL-4Rα), nemolizumab (anti-IL-31RA), anti-OX40/OX40L-antibodies, neurokinin-receptor-1-antagonists, and difelikefalin (κ-opioid-R) are reported."

Journal • Metastases • Review • Atopic Dermatitis • Cardiovascular • Dermatitis • Dermatology • Immunology • Oncology • CD123 • IL13 • JAK1 • JAK2 • TNFSF4

Study on the intervention effect and mechanism of bacillus Calmette-Guerin polysaccharide and nucleic acid injection on atopic dermatitis by targeting the transient receptor potential vanilloid subtype 1 pathway. (PubMed, Ann Transl Med) - "Experiment 1: a total of 30 Kunming (KM) mice were randomized into blank control, model, BCG-PSN low-dose (25 g/kg), BCG-PSN medium-dose (75 g/kg), BCG-PSN high-dose (225 g/kg), and positive drug (hydrocortisone 25 mg/kg) control groups...A total of 20 KM mice were randomized into blank control, model, BCG-PSN, and BCG-PSN + PAC (PAC-14028) groups...In Experiment 2, after BCG-PSN was combined with PAC, the inflammation indexes decreased compared with those in the model group, and increased compared with those in the BCG-PSN group. Intramuscular BCG-PSN can target the TRPV1 pathway, inhibit inflammation, and improve the symptoms of AD mice."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Oncology • IL13 • IL4 • RELA • TNFA • TRPV1

Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: A phase III, randomized, vehicle-controlled study (CAPTAIN-AD). (PubMed, J Allergy Clin Immunol) - "Asivatrep cream ameliorated signs and symptoms, with a favorable safety profile in patients with AD. The first-in-class topical TRPV1 antagonist, asivatrep, might be a promising therapeutic option for AD."

Clinical • Journal • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

EFFICACY AND SAFETY OF ASIVATREP CREAM FOR ATOPIC DERMATITIS: A PLACEBOCONTROLLED, RANDOMIZED PHASE III CLINICAL TRIAL (CAPTAIN-AD)* (ISAD 2021) - P3 | "No significant safety issues were reported. Asivatrep cream was effective and well-tolerated in patients with mild to moderate AD."

Clinical • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

EFFICACY AND SAFETY OF PAC-14028 CREAM, A NOVEL, TOPICAL, NONSTEROIDAL, SELECTIVE TRPV1 ANTAGONIST IN PATIENTS WITH MILD TO MODERATE ATOPIC DERMATITIS: A PHASE IIB RANDOMIZED TRIAL (ISAD 2021) - "No significant safety issues were reported. PAC-14028 cream may be an effective and safe option for the treatment of patients with mild-to-moderate AD."

Clinical • P2b data • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • Sleep Disorder

Novel therapeutic approach with PAC-14028 cream, a TRPV1 antagonist, for patients with mild-to-moderate atopic dermatitis. (PubMed, Br J Dermatol) - No abstract available

Clinical • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial. (PubMed, Br J Dermatol) - "PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD."

Clinical • Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Pruritus

Recent Therapeutic Advances in Pruritus Management for Atopic Dermatitis Patients: A Welcome Addition of Asivatrep to Our Arsenal of Future Topical Treatments. (PubMed, J Cutan Med Surg) - No abstract available

Clinical • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Pruritus

A TRPV1 antagonist, PAC-14028 does not increase the risk of tumorigenesis in chemically induced mouse skin carcinogenesis. (PubMed, Regul Toxicol Pharmacol) - "On Day 169, 1.0% (20 mg/kg/day) of PAC-14028 in female mice resulted in a C and AUC of 12916.0 ng/mL and 78962.9 ng‧hr/mL, respectively. PAC-14028 cream was well tolerated and did not increase the risk of skin tumorigenesis in two-stage carcinogenesis study."

Journal • Preclinical • EGFR

TRPV1 antagonist cream shows promise against eczema in adults (Medscape) - "Dr. Lawrence Eichenfield...told Reuters Health by email that in eczema, 'Transient receptor potential channels can be seen on sensory nerves, as well as other non-nerve cells in the skin. TRPV1 appears to be important in inflammation and itch in atopic dermatitis.' Though this was a small study, Dr. Eichenfield said, it 'suggests an intriguing new potential therapy for atopic dermatitis. Having a non-steroid topical agent that is well tolerated and improves the rash and itch of eczema could be very helpful to minimizing eczema's impact.'"

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