cendakimab (CC-93538) / AbbVie, BMS - LARVOL DELTA

Pruritic rash secondary to cendakimab, an investigative IL-13 inhibitor. (PubMed, JAAD Case Rep) - No abstract available

Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • IL13

Latent Variable Indirect Response Modeling of Cendakimab Exposure-Response for Longitudinal Dysphagia Days Using a Combined Uniform-Binomial Likelihood Framework. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Steroid IR/I and baseline DD influenced treatment response magnitude but did not warrant dose modification. These findings support QW-to-Q2W as an effective maintenance posology and the utility of latent variable IDR models with appropriate likelihoods for modeling bounded, discrete longitudinal endpoints in E-R analyses."

Clinical • Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Inflammatory and fibrotic biomarkers in patients with atopic dermatitis treated with cendakimab. (PubMed, J Allergy Clin Immunol Glob) - P2 | "Compared with placebo, cendakimab resulted in significantly greater reductions in these biomarker levels through week 16. Cendakimab decreased levels of key inflammatory and fibrotic biomarkers over 16 weeks of treatment in patients with moderate-to-severe AD."

Biomarker • Clinical • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • Inflammation • CCL18 • CCL27 • IL13 • IL18 • POSTN

Monoclonal Antibodies' Efficacy on Dysphagia Symptoms and Histological Remission in Patients With Eosinophilic Esophagitis: A Systematic Review and Network Meta-Analysis (ACG 2025) - "We included 5 studies, with 1 study reporting 2 independent trials. Consequently, 6 RCTs comprising 631 patients were included in the final analysis. All RCTs compared monoclonal antibodies with a placebo, with 145 patients treated with dupilumab, 103 received benralizumab, 32 received mepolizumab, 34 received RPC4046, and 317 individuals assigned to the placebo group."

Retrospective data • Review • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • IL13 • IL4 • IL5

A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Participants With Eosinophilic Gastroenteritis (clinicaltrials.gov) - P3 | N=48 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Trial completion • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder

Cendakimab (Anti-IL-13) administration improves esophageal gene expression in eosinophilic esophagitis. (PubMed, J Allergy Clin Immunol) - P2 | "Cendakimab treatment normalizes the aberrant esophageal gene expression seen in patients with EoE, and the changes in transcripts correlate with histologic and endoscopic improvements. The finding that cendakimab corrects esophageal transcript expression even in endoscopic non-responders suggests that the IL-13 pathway is driving EoE pathogenesis in most patients. These collective findings, derived from a multisite, double-blinded, placebo-controlled trial, add molecular evidence that IL-13 drives EoE pathogenesis."

Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • CPA3 • IL13 • POSTN • TPSAB1 • TPSB2

Cendakimab in Adults and Adolescents with Eosinophilic Esophagitis. (PubMed, NEJM Evid) - P3 | "Cendakimab demonstrated statistically significant improvements in symptoms, histologic response, and endoscopic features of EoE versus placebo; the adverse-event and side-effect profile was not dose limiting. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT04753697.)."

Clinical • Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • IL13

Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis (clinicaltrials.gov) - P3 | N=368 | Active, not recruiting | Sponsor: Celgene | N=259 ➔ 368 | Trial primary completion date: Jun 2026 ➔ Aug 2025

Enrollment change • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review. (PubMed, Healthcare (Basel)) - "For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent...Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated...For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments...Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric..."

Journal • Review • Autoimmune Hepatitis • Celiac Disease • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Hepatitis B • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Transplantation • IL13 • IL5 • TGM2 • TSLP

EFFICACY AND SAFETY OF MONOCLONAL ANTIBODIES IN THE TREATMENT OF EOSINOPHILIC ESOPHAGITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (DDW 2025) - "Monoclonal antibodies such as benralizumab, cendakimab, and dupilimumab demonstrate superior efficacy in achieving a histologic response in eosinophilic esophagitis compared to placebo, with cendakimab showing the highest response rate. However, the safety profile varies, with lower risks of adverse events associated with mepolizumab and cendakimab, suggesting a need for individualized treatment strategies."

Retrospective data • Review • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation

Pharmacokinetic Characterization of Cendakimab Administered with Different Devices and at Different Injection Sites in Healthy Participants. (PubMed, Eur J Drug Metab Pharmacokinet) - P1 | "PK parameters of cendakimab were comparable when using PFS or AI. Cendakimab exposures when administered in the arm or thigh resulted in similar exposure; both were ~ 20% higher than when administering in the abdomen. Both PFS and AI were well tolerated. ADA status did not impact the PK or safety of cendakimab."

Journal • PK/PD data

CENDAKIMAB REVERSES THE BIOMARKERS REPRESENTING FIBROTIC TISSUE REMODELING IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: RESULTS FROM A PHASE 3 TRIAL (DDW 2025) - P3 | "As also observed in the phase 2 HEROES trial, CEN significantly reversed EMT and fibrosis biomarkers in this phase 3 trial."

Biomarker • Clinical • P3 data • Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology • CDH1 • IL13 • VIM

A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Participants With Eosinophilic Gastroenteritis (clinicaltrials.gov) - P3 | N=48 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Nov 2026 ➔ Sep 2025

Trial completion date • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder

CENDAKIMAB TREATMENT OF HUMAN ESOPHAGEAL FIBROBLASTS INHIBITS IL-13 INDUCED PATHOGENESIS (DDW 2025) - "Our data demonstrate that cendakimab has protective effects in primary healthy and EoE esophageal fibroblasts for both cytokine production and pro-fibrotic factors. Both IL-13Ra1 and IL-13Ra2 appear functional for mediating the effects of IL-13 on fibroblasts."

Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • IL13 • IL4R • IL6

CENDAKIMAB IS AN EFFECTIVE AND SAFE TREATMENT FOR PATIENTS WITH EOSINOPHILIC ESOPHAGITIS REGARDLESS OF INTERLEUKIN 13 VARIATIONS: RESULTS FROM A PHASE 3 TRIAL (DDW 2025) - P3 | "IL-13 SNP genotypes did not significantly impact efficacy or safety from the respiratory infection standpoint, suggesting that cendakimab is effective and safe in patients with EoE, regardless of the target variations."

Clinical • P3 data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Infectious Disease • Respiratory Diseases • IL13

CENDAKIMAB EFFICACY AND SAFETY IN JAPANESE ADULTS AND ADOLESCENTS WITH EOSINOPHILIC GASTROENTERITIS: 16-WEEK RESULTS FROM THE RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL (DDW 2025) - P3 | No abstract available

Clinical • P3 data • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder

A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Participants With Eosinophilic Gastroenteritis (clinicaltrials.gov) - P3 | N=48 | Active, not recruiting | Sponsor: Celgene | Trial primary completion date: Dec 2023 ➔ Jul 2024

Trial primary completion date • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder

Cendakimab Suppresses Type II Inflammatory Biomarkers And Fibrosis Biomarkers In Atopic Dermatitis (AAAAI-WAO 2025) - P2 | "Conclusions Cendakimab decreased levels of key inflammatory cytokines, chemokines, and tissue remodeling biomarkers over 16 weeks of treatment in patients with AD. These findings suggest that cendakimab modulates pathways of inflammation, fibrosis, and tissue remodeling in AD."

Biomarker • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • Inflammation • CCL18 • CCL27 • IL13 • IL18 • POSTN

Bristol Myers backs out of Dupixent fight, axing allergy asset despite phase 3 win (FierceBiotech) - "Bristol Myers Squibb has continued its ruthless cost-cutting push, dropping plans to commercialize a rival to Dupixent despite meeting its phase 3 goals and pumping the brakes on a would-be Sotyktu successor...Cendakimab fell short of the bar...Last year, BMS reported a phase 3 trial in eosinophilic esophagitis met both co-primary endpoints, positioning the drugmaker to challenge Dupixent and Takeda’s Eohilia for the market...Yet, BMS quietly removed cendakimab from the pipeline in its fourth-quarter update...'Given the data that we have seen, we've made the decision not to commercialize cendakimab'....Similar thinking underpinned BMS’ decision on investing in TYK2."

Commercial • Discontinued • Eosinophilic Esophagitis • Psoriasis

A Study Evaluating Potential Disease-Mediated Drug-Drug Interaction in Adult Participants With Active Eosinophilic Esophagitis Receiving Cendakimab (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Oct 2024

Trial completion • Trial completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

IL-13 inhibition in the treatment of atopic dermatitis - new and emerging biologic agents. (PubMed, J Int Med Res) - "Tralokinumab is approved for use in Europe and the USA, while lebrikizumab is approved only in Europe. Cendakimab, which is another IL-13 selective inhibitor, has shown promising results in phase II trials, providing safe and effective outcomes. Eblasakimab, which disrupts IL-13 and IL-4 signaling pathways, is currently in phase II trials following well-tolerated administration in phase I studies. This narrative review aims to outline the current state of knowledge regarding the effectiveness and safety of these four biologic agents targeting IL-13 signaling."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL13 • IL4

A Study Evaluating Potential Disease-Mediated Drug-Drug Interaction in Adult Participants With Active Eosinophilic Esophagitis Receiving Cendakimab (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Celgene | Trial primary completion date: Jan 2025 ➔ Oct 2024

Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis (clinicaltrials.gov) - P3 | N=259 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Cendakimab Efficacy and Safety in Adult and Adolescent Patients With Eosinophilic Esophagitis 48-Week Results From the Randomized, Placebo-Controlled, Phase 3 Study (Late-Breaking Abstract) (ACG 2024) - P3 | "Overall, 430 pts were randomized to CEN QW/QW (n=143), CEN QW/Q2W (n=143), or PBO (n=144); ~66% of pts were steroid inadequate responders/intolerant. In pts in the CEN QW group (n=286), there were significant improvements in coprimary endpoints of change in DD from BL to wk 24 and eos histologic response ( < 6/hpf) at wk 24 vs PBO (Table). At wk 48, efficacy in secondary endpoints was demonstrated with CEN QW/QW and CEN QW/Q2W vs PBO (Table)."

Clinical • Late-breaking abstract • P3 data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • IL13

Cendakimab Exhibits Robust Anti-Fibrotic Effects by Inhibiting IL-13Rα2 Signaling (ACG 2024) - "Results show that IL-13Rα2 is a signaling receptor whose stimulation with IL-13 leads to the induction of AP-1 in A375 cells. When the parental gene IL13RA2 is knocked out, signaling does not occur. Cendakimab blocks IL-13 induced AP-1 production."

Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology • Inflammation • CCL2 • HGF • IL13 • IL13RA2 • IL6 • POSTN