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

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

CENDAKIMAB EXHIBITS ROBUST ANTI-FIBROTIC EFFECTS BY INHIBITING IL-13RΑ2 SIGNALING (UEGW 2024) - "These experiments confirm that IL-13Rα2 is a signaling cytokine receptor whose engagement leads to the pro-fibrotic activation of primary human fibroblasts. Cendakimab’s potent ability to attenuate this behavior has important implications for its potential value in targeting the fibrostenotic aspects of esophageal dysfunction in EoE [12] and addressing the unmet need of patients suffering from this chronic and progressive disease."

Eosinophilic Esophagitis • Fibrosis • Immunology • Melanoma • Oncology • Solid Tumor • CCL2 • HGF • IL13 • IL13RA2 • IL6 • POSTN

LONG-TERM OUTCOMES OF MAINTENANCE THERAPY IN ADULT AND PEDIATRIC EOSINOPHILIC ESOPHAGITIS: A SYSTEMATIC REVIEW AND METANALYSIS (UEGW 2024) - "Budesonide (either oro-dispersible or viscous suspension) was administered in 7 studies (including 2 RCTs), PPI in 6 studies (all observational, 4 pediatric), Fluticasone in 5 studies (including 1 RCT with 4 cohorts), Dupilumab in 2 RCTs and Cendakimab in 1 RTC. This is the first meta-analysis on efficacy and safety of long-term maintenance treatment (median 78 weeks) for EoE. All treatments showed good efficacy in maintaining long-term histological remission without clear disadvantage in de-escalating therapy during maintenance in real-word data. Biological therapies resulted the most effective in RCTs, while PPIs in observational studies."

Clinical • Review • Candidiasis • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Infectious Disease • Pediatrics

IMPLICATIONS FOR NON-INVASIVE BIOMARKERS OF EOSINOPHILIC ESOPHAGITIS BASED ON RESULTS FROM A PHASE 2 TRIAL OF CENDAKIMAB IN ATOPIC DERMATITIS (UEGW 2024) - P2 | "Cendakimab decreased levels of key inflammatory and 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 and add to the existing clinical evidence of its modulation in other Type 2 inflammatory diseases such as EoE.Table. Least square mean percent change from baseline in key serum biomarker levels at week 16 in patients with AD TreatmentEotaxin-3LS mean percent CFB (95%CI)PeriostinLS mean percent CFB (95%CI)MMP-12LS mean percent CFB (95%CI)Cendakimab 360 mg Q2W–51.53 (–61.98 to –38.20)*,†–47.50 (–56.45 to –36.73)*,†–52.00 (–58.39 to –44.63)*,†Cendakimab 720 mg QW–58.20 (–67.29 to –46.59)*,†–55.76 (–63.31 to –46.67)*,†–54.72 (–60.83 to –47.65)*,†Cendakimab 720 mg Q2W–67.77 (–74.75 to –58.85)*,†–60.93 (–67.57 to –52.94)*,†–61.07 (–66.27 to –55.06)*,†Placebo–5.80 (–26.63 to 20.94)–23.92 (–37.15 to –7.90)*–16.69 (–28.31 to –3.19)*CFB, change..."

Biomarker • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology • IL13 • POSTN

CENDAKIMAB ADMINISTRATION IMPROVES ESOPHAGEAL GENE EXPRESSION IN EOSINOPHILIC ESOPHAGITIS IRRESPECTIVE OF ENDOSCOPIC RESPONSE (UEGW 2024) - P2 | "Molecular analysis of biopsies from patients with EoE demonstrates that after 16 weeks of treatment with cendakimab, endoscopic responders and nonresponders both show improvement in gene expression. Heterogeneous changes in inflammatory-, mast cell-, and epithelial-related genes may impact endoscopic findings. These findings indicate that cendakimab broadly modifies molecular biomarkers even in patients who do not show early endoscopic improvement, raising the possibility that biomarker improvement may precede endoscopic changes in some patients."

Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology • Inflammation • ALOX15 • CPA3 • IL13 • POSTN • TGFB1 • TPSAB1 • TPSB2

COMPARATIVE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF A SINGLE DOSE OF CENDAKIMAB IN HEALTHY CHINESE AND US PARTICIPANTS (UEGW 2024) - P1 | "Single-dose 360 mg or 720 mg SC CEN was safe and well tolerated in all healthy participants. CEN PK was generally dose-proportional for Cmax and AUC from 360 mg to 720 mg. Overall, the PK, tolerability, and safety profiles of a single dose of 360 mg SC CEN in the China study were consistent with those observed in the US study, supporting the use of similar doses across both populations.Table."

Clinical • PK/PD data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • IL13

CENDAKIMAB EFFICACY AND SAFETY IN ADULT AND ADOLESCENT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: 24-WEEK RESULTS FROM THE RANDOMIZED, PLACEBO-CONTROLLED, PHASE 3 STUDY (UEGW 2024) - P3 | "Treatment with CEN demonstrated statistically significant improvement in symptoms and histologic and endoscopic features of EoE vs PBO. CEN was generally safe and well-tolerated through wk 24."

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

Design of a phase 3, randomized, double-blind, placebo-controlled, 48-week study to evaluate the efficacy and safety of cendakimab in adult and adolescent patients with eosinophilic esophagitis. (PubMed, Contemp Clin Trials) - P3 | "This phase 3 pivotal study will determine whether cendakimab provides an effective, safe, targeted treatment for patients with EoE."

Clinical • Journal • P3 data • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Immunology • IL13

A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis (clinicaltrials.gov) - P3 | N=430 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Trial completion • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology