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

CENDAKIMAB REVERSES THE BIOMARKERS REPRESENTING FIBROTIC TISSUE REMODELING IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: RESULTS FROM A PHASE 3 TRIAL (DDW 2025) - No abstract available

Biomarker • Clinical • P3 data • Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology

CENDAKIMAB TREATMENT OF HUMAN ESOPHAGEAL FIBROBLASTS INHIBITS IL-13 INDUCED PATHOGENESIS (DDW 2025) - No abstract available

Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Immunology • IL13

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) - No abstract available

Clinical • P3 data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • 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) - 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

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. (PubMed, JAMA Dermatol) - P2 | "Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment. ClinicalTrials.gov Identifier: NCT04800315."

Clinical • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IL13RA2

A Study Evaluating Potential Disease-Mediated Drug-Drug Interaction in Adult Participants With Active Eosinophilic Esophagitis Receiving Cendakimab (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

LONG-TERM OUTCOMES OF MAINTENANCE THERAPY IN ADULT AND PEDIATRIC EOSINOPHILIC ESOPHAGITIS: A SYSTEMATIC REVIEW AND METANALYSIS (DDW 2024) - "Budesonide (either oro-dispersible or viscous suspension) was administered in 6 studies PPI in 6 studies Fluticasone in 5 studies Dupilumab and Cendakimab both in 1 study. All treatments showed a good efficacy in maintaining histological remission being biological therapies the most effective. Low adverse events and therapy discontinuation rates confirm long-term treatment is well tolerated."

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

IMPLICATIONS FOR NON-INVASIVE BIOMARKERS OF EOSINOPHILIC ESOPHAGITIS BASED ON RESULTS FROM A PHASE 2 TRIAL OF CENDAKIMAB IN ATOPIC DERMATITIS (DDW 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 inflammatory diseases such as EoE."

Biomarker • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Eosinophilic Esophagitis • Fibrosis • Gastrointestinal Disorder • Immunology • IL13 • MMP1 • POSTN