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Choosing the right test

Gaetano Gallo 1

1 University of Catanzaro, Catanzaro, Italy

Event

UEG Week Vienna 2024

Topics

Colorectal Primary Care Surgery

Session

A topic we don't talk about: Evacuation disorders

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Therapy update EoE: Conventional treatment and treatment options for children

Jorge Amil Dias 1, Ulrike von Arnim 2

1 Hospital Lusíadas, Porto - Paed. Gastroenterology, Porto, Portugal

2 Otto-Von Guericke University, Madgeburg, Germany

Event

UEG Week Berlin 2025

Session

Therapy update: EoE

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Podcast Episode

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Best of UEG Week 2024 with Thomas Seufferlein on "Oncology for Gastroenterologists"

Thomas Seufferlein, Julia Mayerle

Topics

Digestive Oncology

Published

2024

UEG Presentation

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Auto-brewery syndrome: A disease model

Gianluca Ianiro 1

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome, Rome, Italy

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine

Session

Breath testing and clinical metabolomics: Back to the future

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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TOWARD A SAFER, NON-SYSTEMIC JAK INHIBITOR FOR IBD: A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PRELIMINAR CLINICAL EFFICACY OF ORAL TREATMENT WITH OST-122 IN PATIENTS WITH ULCERATIVE COLITIS

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Introduction

JAK inhibitors have become an efficacious oral treatment option to antibody-based therapies for ulcerative colitis (UC). However, they have received a black box warning by the FDA for causing serious systemic adverse events.
To increase safety, OST-122 is being developed as an orally administered, GI-targeted and non-systemic JAK3/TYK2 inhibitor for the local treatment of UC. In preclinical models and in healthy volunteers, OST-122 has demonstrated excellent safety and tolerability with minimal systemic exposure reducing the risk of causing serious systemic toxicities associated with current JAK inhibitors.
Here, we report the results of a phase 2a study in patients with UC on the safety, tolerability, pharmacokinetics and preliminary efficacy of OST-122.

Aims & Methods

In this randomized, double-blind trial, 37 adult patients with active UC were treated with oral OST-122 400 mg (n=28) or placebo (n=9) for 28 days. Eligibility criteria required a total Mayo Score TMS 5-10, endoscopic Mayo Score EMS ≥2, inadequate/loss of response to conventional therapy (5-ASA, steroids, immunomodulators) or biologics (anti-TNFα, anti-integrin, anti-interleukin 12/23). Stable cotreatment with oral 5’ASAs and corticosteroids was permitted.
To evaluate the safety and tolerability of OST-122, the number and severity of AEs, including changes in vital signs, safety laboratory values and ECGs, were analyzed. Plasma, tissue and stool samples were collected at various time points to examine the gut-restricted pharmacokinetic profile of the compound in UC patients. Preliminary efficacy was assessed through Mayo Clinical Scores including rectal bleeding (RB) and stool frequency (SF) along with clinical response and remission.

Results

During the 6-week observation period, no serious AEs nor treatment-related AEs leading to discontinuation were reported. Most AEs were tabulated as mild, followed by moderate, and the number of subjects reporting AEs were distributed equally in the placebo and OST-122 group (78% vs. 71%). There were no clinically relevant changes in vital signs, laboratory values or ECG parameters which raise any safety concerns.
Pharmacokinetic analysis indicated minimal plasma concentrations (C_max 0.92 ng/mL) and therapeutically relevant levels in colon tissue (15.5 ug/g tissue) confirming a gut-restricted PK profile of OST-122.
Preliminary efficacy data after 28 days of treatment are summarized in the table below:

Outcome	400 mg OST-122 (n=28)	Placebo (n=9)	∆
Rectal Bleeding Improvement of RB score by ≥1	63% (17/27)	33% (3/9)	33%
Stool Frequency Improvement of SF score by ≥1	52% (14/27)	33% (3/9)	19%
PRO-2 score (RB + SF) Improvement of PRO-2 by ≥2	48% (13/27)	11% (1/9)	37%
Clinical Response Decrease of TMS by ≥3 or ≥30 %, plus improvement in RB by ≥1 and an absolute RB of 0 or 1	44% (12/27)	11% (1/9)	33%
Clinical Remission TMS ≤2 and no individual subscore >1, plus RB of 0	22% (6/27)	0% (0/9)	22%

63% of patients taking OST-122 showed an improvement in rectal bleeding and 52% in stool frequency (vs 33% in the placebo group), and 48% had an improvement of ≥2 in PRO-2 (RB+SF, vs 11% Pbo). Clinical response was achieved by 44% (vs 11% Pbo) and 22% reached clinical remission (vs 0% Pbo). In addition, 16% of patients in the OST-122 group achieved both histological response and remission (vs 0% Pbo). A subgroup analysis showed that OST-122 was able to induce clinical response both in bionaïve and bioexperienced patients. Confirmatory studies will be designed to determine dose and statistical significance.

Conclusion

GI-restricted OST-122 was well tolerated during the 4-week treatment. Its excellent safety profile, minimal systemic exposure and promising trends of clinical activity may provide a safer therapeutic option for a broad range of ulcerative colitis patients.

Disclosure

M. Barreiro de Acosta has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte, Vifor Pharma and Oncostellae.
C. Rodríguez has received consultancy and/or speaking honoraria fees from AbbVie, Ferring, Galapagos, Janssen, Pfizer, Lilly and Takeda.
M.D. Martin-Arranz has received fees as a speaker, consultant and advisory member for or has received funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Shire Pharmaceuticals, Tillots Pharma, and Faes Pharma.
L. Torrealba has served as a speaker for Janssen.
E. Iglesias Flores has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, Takeda, Gillead, Celgene, Pfizer, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, and Adacyte.
F. Argüelles-Arias has served as a speaker, consultant and advisory member or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma.
Y. Ber-Nieto has served as a speaker from Abbvie and has received education funding from Abbvie and Pfizer.

TOWARD A SAFER, NON-SYSTEMIC JAK INHIBITOR FOR IBD: A PHASE 2A STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PRELIMINAR CLINICAL EFFICACY OF ORAL TREATMENT WITH OST-122 IN PATIENTS WITH ULCERATIVE COLITIS

Manuel Barreiro-De Acosta 1, Svitlana Skybalo 2, Cristina Rodríguez Gutiérrez 3, Santiago García-López 4, María Dolores Martín-Arranz 5, Leyanira Torrealba 6, Eva Iglesias-Flores 7, Federico Argüelles-Arias 8, Yolanda Ber Nieto 9, Viktoriia Shevchuk 10, Cristina Castro Fernández 11, Julio César Castro-Palomino 11, Ascensión Heredia 11, Guido Kurz 11

1 Hospital Clínico Universitario de Santiago De Compostela, Santiago de Compostela, Spain

2 Medical Center “Ok!Clinic” of International Institute of Clinical Research LLC, Kyiv, Ukraine

3 Complejo Hospitalario Universitario de Navarra, Pamplona, Spain

4 Hospital Universitario Miguel Servet, Zaragoza, Spain

5 Hospital Universitario La Paz, Madrid, Spain

6 Hospital Universitario Dr. Josep Trueta, Girona, Spain

7 Hospital Universitario Reina Sofía, Córdoba, Spain

8 Universidad de Sevilla, Hospital Universitario Virgen Macarena, Sevilla, Spain

9 Hospital Universitario San Jorge, Huesca, Spain

10 Medical and Diagnostic Center PE PMC "Acinus", Kropyvnytskyi, Ukraine

11 Oncostellae S.L., Santiago de Compostela, Spain

Event

UEG Week Vienna 2024

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

IBD: New horizons in medical treatment - Part 2

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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Artificial intelligence in endoscopy

Yuichi Mori 1

1 University of Oslo / Showa University, Oslo, Norway

Event

UEG Week Copenhagen 2023

Topics

Endoscopy Mechanisms & Personalised Medicine Radiology & Imaging Surgery

Session

Digestive diseases: Help from the machines?

Published

2023

UEG Presentation

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CENDAKIMAB EFFICACY AND SAFETY IN ADULT AND ADOLESCENT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: 24-WEEK RESULTS FROM THE RANDOMIZED, PLACEBO-CONTROLLED, PHASE 3 STUDY

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Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, immune-mediated inflammatory disease characterized by esophageal inflammation with infiltration of eosinophils (eos) and symptoms of esophageal dysfunction. Interleukin (IL)-13, a type 2 inflammatory cytokine, plays a key role in the pathophysiology of EoE. Cendakimab (CEN) is a recombinant, humanized, high-affinity, neutralizing monoclonal antibody targeting IL-13, inhibiting binding to both its receptors, IL-13Rα1 and IL-13Rα2. CEN reduced mean esophageal eos counts and improved symptoms and endoscopic features of EoE in a phase 2 study. We report results from a pivotal phase 3 trial (NCT04753697) of CEN in adult and adolescent patients (pts) with EoE after 24 wk of treatment.

Aims & Methods

This multicenter, multinational, randomized, double-blind, placebo (PBO)-controlled study enrolled pts aged 12–75 y with active EoE (peak esophageal eos count [PEC] ≥ 15 eos/high power field [hpf] at any 2 levels of the esophagus), ≥ 4 dysphagia days (DD) over the 14-day period prior to day 1 evaluated using the modified Daily Symptom Diary (mDSD), and lack of complete response to ≥ 8 wk proton pump inhibitor treatment. The study planned to enroll ~70% of pts who were steroid inadequate responders or intolerant (steroid IR/I). Pts were randomized 1:1:1 to receive subcutaneous CEN 360 mg weekly for 48 wk (QW/QW), CEN 360 mg QW for 24 wk followed by CEN 360 mg every other wk for 24 wk (QW/Q2W), or PBO QW for 48 wk. Coprimary endpoints were mean change from baseline (BL) to wk 24 in DD and proportion of pts with eos histologic response, defined as PEC ≤ 6/hpf at wk 24. Key secondary endpoints included eos histologic response < 15/hpf at wk 24, endoscopic response (mean change in Endoscopic Reference Score [EREFS] total score), mean change in EoE Histology Scoring System (EoEHSS) grade/stage score, and mean change in mDSD composite score, from BL to wk 24. Safety was also evaluated.

Results

Overall, 430 pts (~66% steroid IR/I) were randomized to CEN (n = 286; QW/QW, n = 143, QW/Q2W, n = 143), or PBO (n = 144). In pts treated with CEN 360 mg QW, there was a statistically significant reduction from BL to wk 24 in DD vs PBO (−6.1 vs −4.2 days; difference [95% CI] vs PBO: −1.9 [−3.0 to −0.8]; P = 0.0005) and a statistically significantly higher proportion of pts with eos histologic response at wk 24 vs PBO (28.6% vs 2.2%; difference [95% CI] vs PBO: 26.4 [20.6 to 32.2]; P < 0.0001) (Table). Statistically significant improvements in all key secondary endpoints were observed for CEN-treated vs PBO-treated pts (Table). At wk 24, adverse events (AE) related to study drug occurred in 30.3% and 18.9% of pts in the CEN and PBO arms, with AEs leading to discontinuation in 1.4% and 0.7% of pts, respectively. No deaths occurred.

Table. Efficacy results at wk 24

	Treatment	CEN 360 mg QW (n = 286)	PBO QW (n = 144)	Difference (95% CI); P value
Coprimary endpoints	LS mean change from baseline in DD	−6.1	−4.2	−1.9 (−3.0 to −0.8); P = 0.0005
Coprimary endpoints	Patients with eos histologic response (≤ 6/hpf), %	28.6	2.2	26.4 (20.6 to 32.2); P < 0.0001
Key secondary endpoints	Patients with eos histologic response (< 15/hpf), %	43.1	3.1	40.0 (33.3 to 46.7); P < 0.0001
	LS mean change in EREFS^a total score	−5.2	−1.2	−4.0 (−4.8 to −3.2); P < 0.0001
	LS mean change in EoEHSS grade score	−26.2	−3.7	−22.5 (−25.5 to −19.5); P < 0.0001
	LS mean change in EoEHSS stage score	−31.7	−6.3	−25.4 (−28.9 to −21.9); P < 0.0001
	LS mean change in mDSD composite score	−12.8	−8.7	−4.1 (−6.4 to −1.8); P = 0.0005
^aEREFS is a validated approach for assessing the presence and severity of the major endoscopic features of EoE. EREFS were scored on a 0-8 point scale (edema [0–1], rings [0–3], exudates [0–2], furrows [0–1], and stricture [0–1]) at 3 levels of the esophagus (proximal, mid, and distal), with total score range of 0–24. LS, least squares.

Conclusion

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.

Disclosure

AS has served a consultant for Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; and has received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. CMC, SZ, KL, AV, AY, and YSO are employees and shareholders of Bristol Myers Squibb. CLZ is a contractor to Bristol Myers Squibb. ESD has served as a consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Bryn, Calypso, Celgene/Receptos/Bristol Myers Squibb, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; has received grant/research support from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/Bristol Myers Squibb, Regeneron, Revolov, and Shire/Takeda; and has received educational grants from Allakos, Aqilion, Holoclara, and Invea. GF has served as a consultant for Adare/Ellodi, Allakos, Celgene/Receptos/Bristol Myers Squibb, LucidDx, Nexstone Immunology/Uniquity, Phathom, Regeneron/Sanofi, Shire/Takeda, and Upstream Bio; has received grant/research support from Adare/Ellodi, Allakos, Arena/Pfizer, Celldex, Celgene/Receptos/Bristol Myers Squibb, Regeneron, Sanofi, Revolov, and Shire/Takeda. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer. HP has served as a consultant for Dr. Falk Pharma, Arena/Pfizer, GSK and Abbott. TV is a speaker for Dr. Falk Pharma and Bristol Myers Squibb; consultancy for Dr. Falk Pharma, Bristol Myers Squibb; research grant from Dr. Falk Pharma. SO has served a consultant for Dr. Falk Pharma, Medtronic, Regeneron/Sanofi, Celgene/Receptos/Bristol Myers Squibb; and has received grant/research support from Medtronic, Regeneron/Sanofi, Alfasigma.

CENDAKIMAB EFFICACY AND SAFETY IN ADULT AND ADOLESCENT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: 24-WEEK RESULTS FROM THE RANDOMIZED, PLACEBO-CONTROLLED, PHASE 3 STUDY

Alain M. Schoepfer 1, Christina Charriez 2, Sandra Zhang 2, Gary Falk 3, Salvatore Oliva 4, Christopher Ma 5, Jesse Siffledeen 6, Shauna Schroeder 7, Hamish Philpott 8, Tim Vanuytsel 9, Christel Contzen 10, Yasuhiko Abe 11, Kexuan Li 2, Carla L. Zema 2, Ashwini Venkatasamy 2, Anusha Yeshokumar 2, Young S. Oh 2, Evan S. Dellon 12

1 Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

2 Bristol Myers Squibb, Princeton, United States

3 Perelman Center for Advanced Medicine, University Of Pennsylvania, Bryn Mawr, United States

4 Azienda Policlinico Umberto I, Rome, Italy

5 University of Caglary, Calgary, Canada

6 South Edmonton Gastroenterology, Edmonton, Canada

7 Phoenix Children’s Hospital, Phoenix, United States

8 Department of Gastroenterology Lyell McEwin Hospital, Northern Adelaide Local Health Network (NALHN), University of Adelaide, Adelaide, Australia

9 UZ Leuven, Leuven, Belgium

10 AES – DRS – Synexus, Frankfurt, Germany

11 Yamagata University Hospital, Yamagata, Japan

12 University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, United States

Event

UEG Week Vienna 2024

Topics

Endoscopy IBD Mechanisms & Personalised Medicine Oesophagus

Submission format

Late-Breaking Abstract

Session

From IBS and IBD: Late-breaking abstracts

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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