fezakinumab (ILV-094) / Pfizer - LARVOL DELTA

IL-22 in Atopic Dermatitis. (PubMed, Cells) - "Elevated levels of IL-22 in patients with AD are correlated with increased proliferation of keratinocytes, alterations in the skin microbiota, and impaired epidermal barrier function. Collectively, these factors contribute to the manifestation of the characteristic symptoms observed in AD."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Inflammation • IL22

Interplay of cytokines in the pathophysiology of atopic dermatitis: insights from Murin models and human. (PubMed, Front Med (Lausanne)) - "Dupilumab, which targets IL-4 and IL-13, has shown efficacy in treating moderate to severe AD. Nemolizumab, targeting IL-31RA, effectively reduces pruritus in AD patients. In addition, clinical trials with fezakinumab, targeting IL-22, have demonstrated promising results, particularly in severe AD cases...Similarly, thymic stromal lymphopoietin (TSLP), integral to type 2 immune responses, induces dermatitis in animal models and is elevated in human AD, yet clinical treatments like tezepelumab exhibit limited efficacy...Consequently, this review delineates the distinct roles of cytokines in the pathogenesis of AD, juxtaposing their significance in human AD from clinical trials against insights gleaned from AD mouse models. This approach will improve our understanding of interspecies variation and facilitate a deeper insight into the pathogenesis of AD in humans."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • CD123 • FLG • IL13 • IL17A • IL22 • IL33 • IL4 • IL5 • TSLP

Differentiation of IL-22 levels in inflammatory diseases using a high sensitivity ELISA (RAD 2023) - "Furthermore, IL-22 protein has been proposed as a stratification biomarker for psoriatic arthritis therapeutic choice between IL-17 and TNF inhibitions10, to correlate with the severity of clinical sequelae of Sjogren's Syndrome11, and IL-22 mRNA expression stratifies AD responses to fezakinumab9...Should this trend toward IL-22 elevation be fully substantiated in AD, therapeutic stratification and precision medicine approaches may be conceivable based on serum IL-22 protein concentrations, supporting other investigators' earlier work examining IL-22 mRNA9 . The baseline readability of endogenous IL22 in HD sera using this ELISA is also highly advantageous."

Late-breaking abstract • Atopic Dermatitis • Crohn's disease • Cystic Fibrosis • Dermatitis • Dermatology • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Lupus • Psoriasis • Psoriatic Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Sjogren's Syndrome • Systemic Lupus Erythematosus • CD8 • IL10 • IL17A • IL22

Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis (clinicaltrials.gov) - P2; N=60; Completed; Sponsor: Rockefeller University; Active, not recruiting ➔ Completed; N=20 ➔ 60; Trial completion date: Jun 2019 ➔ Jan 2019

Clinical • Enrollment change • Trial completion • Trial completion date

Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas. (PubMed, Int J Mol Sci) - "Our aim was to review the literature on interleukins 4, 13, 22, and 31, and JAK/STAT pathways in PCLs to elucidate the safety of using biologics (dupilumab, tralokinumab, fezakinumab, nemolizumab) and small molecule inhibitors (upadacitinib, baricitinib, abrocitinib, ruxolitinib, tofacitinib) in the treatment of atopic dermatitis. This issue requires further study and meticulous monitoring of patients receiving these drugs to ensure their safety, especially in light of the FDA warning on tofacitinib. In conclusion, in the case of the rapid progression of atopic dermatitis/eczema, especially in patients older than 40 years old, there is a necessity to perform a biopsy followed by a very careful pathological examination."

Clinical • Journal • Review • Atopic Dermatitis • Cutaneous T-cell Lymphoma • Dermatitis • Dermatology • Hematological Malignancies • Immunology • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome

Novel therapies in the treatment of atopic dermatitis (PubMed, Pol Merkur Lekarski) - "Dupilumab, which long-term effectiveness and safety have been proven, is the first biologic available for atopic dermatitis. Other monoclonal antibodies such as nemolizumab, tralokinumab, lebrikizumab and fezakinumab demonstrated statistically significant clinical improvements in phase 2 and 3 trials...JAK inhibitors such as abrocitinib, baricitinib and upadacitinib showed promising effects in improvement of skin lesions and itch reduction...Thus, during SARS-CoV-2 infection it might be safer to use JAK inhibitors in case of necessity of a rapid immune response. There is a need to differentiate subtypes of atopic dermatitis, based on clinical symptoms and inflammatory mediators to choose an optimal therapeutic option for each patient."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Transcriptomic drug-response gene signatures are informative for the stratification of patients for clinical trials. (PubMed, J Allergy Clin Immunol) - No abstract available

Clinical • Journal • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] A computational model suggested potential therapies for dupilumab poor responders in atopic dermatitis (ESDR 2021) - "To investigate promising therapies in dupilumab poor responders, we developed a computational model that describes systemslevel AD pathogenesis and effects of nine biologics (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma). The model will serve as a computational platform for model-informed drug development for precision medicine, as it allows to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients. Similar mathematical models and simulation can be also applicable for other diseases and therapies when there are reported clinical efficacies of multiple drugs."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

Novel Targeted Biological Agents for the Treatment of Atopic Dermatitis. (PubMed, BioDrugs) - "If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered...Dupilumab is the first biological agent approved for the treatment of AD in patients aged 6 years and older in the United States. Tralokinumab, lebrikizumab, and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials. Also, fezakinumab was effective in severe AD patients in a phase IIa trial. However, phase II trials of ustekinumab, tezepelumab, etokimab, secukinumab, and omalizumab have failed to meet their primary endpoints. Phase II trials of GBR 830 and KHK 4083 are ongoing. In general, further studies are needed to explore new therapeutic targets and improve the efficacy of biological agents."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immune Modulation • Immunology • Inflammation • IL13 • IL17A • IL33 • TSLP

A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis. (PubMed, Allergy) - "Our model identified IL-13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL-13 and IL-22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model-informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

Mapping atopic dermatitis and anti-IL-22 response signatures to Type 2-low severe neutrophilic asthma. (PubMed, J Allergy Clin Immunol) - "The FZ-response signature in AD identifies severe neutrophilic asthmatics as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases."

Journal • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pulmonary Disease • Respiratory Diseases • IL22

A COMPUTATIONAL MODEL TO INVESTIGATE DRUG TARGETS IN AD PATIENTS WITH HETEROGENOUS RESPONSE TO BIOLOGIC DRUGS (ISAD 2021) - "To understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, we conducted model-based meta-analysis of clinical trials data and developed a mathematical model that describes systems-level AD pathogenesis and effects of nine biologic drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma). The mathematical model will serve as a computational platform for model-informed drug development for precision medicine, as it allows us to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients as well as the influence of pathophysiological backgrounds of patients on variability in drug response. Similar mathematical models can be developed for other diseases and drugs by conducting model-based meta-analysis on reported clinical efficacies of multiple drugs."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IFNG • IL13 • IL22

COMPARING CUTANEOUS MOLECULAR AND CLINICAL IMPROVEMENT WITH DIFFERENT TREATMENTS IN ATOPIC DERMATITIS PATIENTS (ISAD 2021) - "Our objective was to identify an evidence-based approach to gauge therapeutic responses for individual AD patients, incorporating clinical and skin biomarker evaluations from studies with broad (cyclosporine, narrow-band ultraviolet B/NB-UVB, corticosteroids, ASN002/anti-JAK-SYK, crisaborole), and more targeted agents (dupilumab, fezakinumab/anti-IL-22). For instance, baseline CCL22 expression correlated with future clinical improvement across multiple treatments, including crisaborole, cyclosporine, and fezakinumab. This study advocates for combining clinical data and objective skin biomarkers to increase the ability to gauge responses in clinical trials and develop a precision medicine approach."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL2 • CCL22 • IL22 • SYK

OVERVIEW OF NEW THERAPIES IN AD (ISAD 2021) - "New topical anti-inflammatory agents include the topical phosphodiesterase inhibitor crisaborole and the aryl hydrocarbon receptor agonist tapinarof...The IL-4/ IL-13 receptor blocker dupilumab is a safe and effective treatment option with potential ocular and some on-target side effects, licensed from the age of 6 years...The IL-13-blockers tralokinumab and lebrikizumab target also the Th2 pathway...The IL-31 receptor blocker nemolizumab reduces itch excellently and improves visible lesions, too...Fezakinumab (anti-IL-22), etokimab (anti-IL-33), and tezepelumab (anti-TSLP) have been investigated in smaller proof-of-concept studies for the indication atopic dermatitis. A number of different, fast acting Janus kinase inhibitors, such as Baricitinib, Abrocitinib and Upadacitinib are emerging treatment options differing in efficacy, safety profile and licensing status. Licensed systemic antihistamines (H1R-blockers) only have limited effects on AD related itch and eczema..."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics • IL13 • IL22 • IL4

Improving evaluation of drugs in atopic dermatitis by combining clinical and molecular measures. (PubMed, J Allergy Clin Immunol Pract) - No abstract available

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

[VIRTUAL] Comparing molecular cutaneous improvement in atopic dermatitis with various treatment modalities facilitates personalized approaches (SID 2020) - "Using a meta-analysis-based approach, we are comparing immune and barrier effects of key systemic treatments used or tested in AD, including cyclosporine A, narrow-band ultraviolet B, dupilumab/anti IL-4R, fezakinumab/anti-IL-22, ASN002/JAK-SYK antagonist, ustekinumab/anti IL-12/23p40, as well as topicals (topical corticosteroids, crisaborole/anti PDE4) on lesions of AD patients. For example, Th22/IL-22 targeting with fezakinumab is particularly efficacious in improving the AD barrier dysfunction, but induces only modest changes in skin inflammation. Our approach may facilitate future development of a personalized medicine approach in AD by identifying the best treatments for individual phenotypes and patients needs, based on immune, barrier, and atherosclerosis profiles."

Atherosclerosis • Atopic Dermatitis • Cardiovascular • Dermatitis • Dermatology • Dermatopathology • Dyslipidemia • Immunology • IL12A • SYK

Novel Therapeutic Approaches and Targets for Treatment of Atopic Dermatitis. (PubMed, Curr Pharm Biotechnol) - "The extreme clinical heterogeneity and the chronic progression of Atopic Dermatitis need for newer, safer and more effective treatments, able to control the disease and to improve the quality of life of affected patients. Dupilumab, and the other monoclonal antibodies and small molecules currently under investigation aim to improve the clinical management of Atopic Dermatitis."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • IL13 • IL17A • IL4 • IL5

Review and analysis of biologic therapies currently in phase II and phase III clinical trials for atopic dermatitis. (PubMed, J Dermatolog Treat) - "Further assessment of tezepelumab and etokimab are needed to assess their safety and efficacy in patients with moderate-to-severe AD. Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD."

Clinical • Journal • P2 data • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis (clinicaltrials.gov) - P2; N=20; Active, not recruiting; Sponsor: Rockefeller University; N=60 ➔ 20; Trial completion date: Jun 2018 ➔ Jun 2019

Enrollment change • Trial completion date • Atopic Dermatitis • Biosimilar • Dermatitis • Dermatology • Immunology • Inflammation

Efficacy of biologics in atopic dermatitis. (PubMed, Expert Opin Biol Ther) - "Recent advancements in understanding AD pathogenesis resulted in the exponential expansion of its therapeutic pipeline, particularly following the success and FDA-approval of dupilumab...Nevertheless, this biologic does not work for everyone, highlighting the need for a more precise approach to address the unique immune fingerprints of each AD subset. Ultimately targeted therapeutics will complement our understanding of the AD molecular map and help push AD management into an era of personalized medicine."

Clinical • Journal

Comparing cutaneous molecular improvement with different treatments in atopic dermatitis patients. (PubMed, J Allergy Clin Immunol) - "This is the first study that objectively compares the molecular cutaneous improvement with different treatments in AD and may facilitate personalized medicine by identifying the best treatments for individual phenotypes, based on immune/barrier profiles."

Clinical • Journal

Baseline IL22 expression in atopic dermatitis patients stratifies tissue responses to fezakinumab. (PubMed, J Allergy Clin Immunol) - "Stratification of cytokine expression at baseline might help future precision medicine approaches to effectively treat atopic dermatitis patient subsets that might benefit from IL-22 antagonism or other specific blockers."

Clinical • Journal

The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis. (PubMed, Front Immunol) - "Clinical trials that investigate inhibitors of IL-20 (fletikumab) and IL-22 (fezakinumab) in psoriasis and RA have been terminated. All IL-20 family members utilize the Janus kinase signaling pathway and are therefore potentially inhibited by drugs targeting these enzymes. Effects and adverse effects in ongoing clinical trials with inhibitors of IL-22 and the IL-22RA1 subunit and recombinant IL-22 fusion proteins will possibly provide important information about the IL-20 subfamily of cytokines in the future."

Journal • Review

Is Fezakinumab, an anti-IL22 antibody, a putative novel therapy for a subset of severe asthma? (ERS 2019) - "A subset of asthmatics may respond to anti-IL-22 antibody therapy. While the role of IL-22 in asthma remains to be elucidated,our study indicates that AD and a subset of asthma patients may share IL-22 pathways. Reference; 1Brunner P etal.JACI 2019 143(142-154)"

What's New in Atopic Dermatitis. (PubMed, Dermatol Clin) - "Nevertheless, because not all patients respond to dupilumab and AD has a heterogeneous phenotype, more treatment options are much needed. This article reviews recent and exciting developments in AD, because ongoing or pipeline clinical trials for AD will ultimately expand and redefine a novel treatment paradigm for this common disease."

Journal • Review