P5324 - Duvakitug, an anti-TL1a mAb, Demonstrates Efficacy and Favorable Safety as an Induction Treatment in Adults With Moderately to Severely Active Ulcerative Colitis: Results From the RELIEVE UCCD Phase 2b Basket Trial

Award: ACG Presidential Poster Award

Walter Reinisch, MD, PhD¹, David Štěpek, MD², Radoslaw Kempinski, MD, PhD³, Silvio Danese, MD, PhD⁴, Bruce E. Sands, MD, MS, FACG⁵, Bogdan Ratiu-Duma, ⁶, Rajendra Singh, PhD⁷, Hadas Barkay, PhD⁸, Gordon Raphael, MD⁹, Vipul Jairath, MBChB, DPhil, MRCP¹⁰
1Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Spitalgasse, Wien, Austria; 2Military Hospital Brno, Internal Department, Brno, Jihomoravsky kraj, Czech Republic; 3Wrocław Medical University, Wrocław, Lubelskie, Poland; 4Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Lombardia, Italy; 5Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA, New York, NY; 6Teva Pharmaceuticals S.R.L., Pharmacovigilance, Bucharest, Bucuresti, Romania; 7Teva Branded Pharmaceutical Products, Research and Development, West Chester, PA; 8Teva Pharmaceutical Industries Ltd., Research and Development, Netanya, HaDarom, Israel; 9Teva Pharmaceutical Industries Ltd, West Chester, PA; 10Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

Introduction: Duvakitug is a human IgG1 monoclonal antibody selected for its preferential inhibition of TL1A-DR3 signaling over DcR3 binding. Duvakitug has demonstrated reduced inflammation and fibrosis in colitis animal models.¹ The efficacy and safety of duvakitug in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease was assessed in a phase 2b basket trial (NCT05499130).

Methods: RELIEVE UCCD was a randomized, placebo (PBO)-controlled, double-blind induction study. The UC cohort comprised of adults with moderately to severely active disease with inadequate response, loss of response or intolerance to previous conventional and/or advanced therapies (ATs). Eligible patients were randomized to receive subcutaneously a 2250 mg loading dose of duvakitug or PBO, followed by either duvakitug 450 mg, 900 mg or PBO (1:1:1; stratified by prior AT) every 2 weeks. The primary endpoint was clinical remission (per modified Mayo score) at week 14. Safety was assessed by adverse event (AE) reporting and laboratory monitoring.

Results: In total, 137 patients were randomized, treated and included in the UC cohort analysis (450 mg: n=47; 900 mg: n=46; PBO: n=44). Demographics and baseline characteristics were generally similar across arms (Table 1). Both duvakitug doses successfully achieved the week 14 primary endpoint of clinical remission (36% [450 mg], 48% [900 mg] versus 20% [PBO]; PBO-adjusted rates: 16% [450 mg], 27% [900 mg]). The results were statistically significant based on the prespecified Bayesian analysis, with a >0.90 posterior probability that each duvakitug dose is superior to PBO. Duvakitug treatment effect was observed in both AT-experienced and -naïve patients (Table 2). AE incidence was lower for duva­kitug (49% [450 mg], 43% [900 mg]) versus PBO (52%), as was incidence of AEs leading to discontinuation (0% [450 mg], 2% [900 mg] vs 5% [PBO]).

Discussion: Duvakitug demonstrated statistically significant and clinically meaningful treatment responses compared to PBO in patients with UC; it was well tolerated with no emergent safety signals observed. These induction study results support further development of duvakitug as a potential treatment option for patients with moderately to severely active UC.


Reference:

1. Clarke AW, et al. MAbs. 2018;10:664–77


Figure: Table 1: Demographics and baseline characteristics
Advanced therapies include approved therapies: biologics (TNF inhibitors, integrins inhibitors, IL-12/23 inhibitors or anti-IL-23), JAK inhibitors and S1P receptor modulators. Drugs currently in development for IBD are included in the investigational drugs category. Percentages may not add up to 100 due to rounding.


Figure: Table 2: Week 14 clinical remission rates (per modified Mayo score)
Advanced therapy experience includes prior exposure to approved biologics, S1P receptor modulators and/or JAK inhibitors. Percentages may not add up due to rounding.

Disclosures:
Walter Reinisch: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support. Actelion – Advisory Committee/Board Member, Consultant. Alpha Wasserman – Advisory Committee/Board Member, Consultant. AstraZeneca – Advisory Committee/Board Member, Consultant. Cellerix – Advisory Committee/Board Member, Consultant. Cosmo Pharmaceuticals – Advisory Committee/Board Member, Consultant. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Grunenthal – Advisory Committee/Board Member, Consultant. Johnson & Johnson – Advisory Committee/Board Member, Consultant. Merck – Advisory Committee/Board Member, Consultant. Millennium – Advisory Committee/Board Member, Consultant. Novo Nordisk – Advisory Committee/Board Member, Consultant. Nycomed – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pharmacosmos – Advisory Committee/Board Member, Consultant. Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant. Schering-Plough – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant. UCB Pharma – Advisory Committee/Board Member, Consultant. Vifor Pharma – Advisory Committee/Board Member, Consultant.
David Štěpek indicated no relevant financial relationships.
Radoslaw Kempinski: AbbVie – Lecture fees. Aboca S.p.A. Società Agricola – Lecture fees. Eli Lilly and Company – Lecture fees. Ferring – Lecture fees. Takeda – Grant/Research Support.
Silvio Danese: AbbVie – Consultant, Lecture fees. Alimentiv – Consultant. Allergan – Consultant. Amgen – Consultant, Lecture fees. AstraZeneca – Consultant. Athos Therapeutics – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. Enthera – Consultant. F. Hoffmann-La Roche Ltd – Consultant. Ferring Pharmaceuticals Inc. – Consultant, Lecture fees. Gilead – Consultant, Lecture fees. Hospira – Consultant. Inotrem – Consultant. Johnson & Johnson – Consultant, Lecture fees. MSD – Consultant. Mundipharma – Consultant. Mylan – Consultant, Lecture fees. Pfizer – Consultant, Lecture fees. Sandoz – Consultant. Sublimity Therapeutics – Consultant. Takeda – Consultant, Lecture fees. TiGenix – Consultant. UCB Inc. – Consultant. Vifor (International) Ltd. – Consultant.
Bruce Sands: AbbVie – Consultant. Abivax – Consultant, speaking fees. Adiso Therapeutics – Consultant. Agomab Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. AnaptysBio – Consultant. Arena Pharmaceuticals – Consultant. Artugen Therapeutics – Consultant. Astra Zeneca – Consultant. Biolojic Design – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees. Calibr – Consultant. Celgene – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Eli Lilly & Company – Consultant, speaking fees. Enthera – Consultant. Enveda Biosciences – Consultant. Equillium – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Fzatat – Consultant. Galapagos – Consultant. Genentech (Roche) – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. Imhotex – Consultant. Index Pharmaceuticals – Consultant. Innovation Pharmaceuticals – Consultant. Inotrem – Consultant. Janssen R&D – Consultant, Grant/Research Support, speaking fees. Kaleido – Consultant. Kallyope – Consultant. Merck & Co., Inc., Rahway, NJ, USA – Consultant. Microba – Consultant. Mobius Care – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. Nexus Therapeutics – Consultant. Nimbus Discovery – Consultant. Odyssey Therapeutics – Consultant. Pfizer – Consultant, Grant/Research Support, speaking fees. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. Rasayana Therapeutics – Consultant. Recludix Therapeutics – Consultant. Reistone Biopharma – Consultant. Sanofi – Consultant. Spyre Therapeutics – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support, speaking fees. Target RWE – Consultant. Teva – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. Tr1X – Consultant. Union Therapeutics – Consultant. Ventyx Biosciences – Consultant, Stock Options.
Bogdan Ratiu-Duma: Teva – Employee.
Rajendra Singh: Teva – Employee.
Hadas Barkay: Teva – Employee.
Gordon Raphael: Teva – Employee.
Vipul Jairath: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Alimentiv – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Asahi Kasei Pharma – Consultant, Grant/Research Support, Speakers Bureau. Asieris Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. AstraZeneca – Consultant, Grant/Research Support, Speakers Bureau. Avoro Capital – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, Speakers Bureau. Celltrion – Consultant, Grant/Research Support, Speakers Bureau. Eli Lilly and Company – Consultant, Grant/Research Support, Speakers Bureau. Endpoint Health – Consultant. Enthera – Consultant. Ferring Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Flagship Pioneering – Consultant, Grant/Research Support, Speakers Bureau. Fresenius Kabi – Consultant, Grant/Research Support, Speakers Bureau. Galapagos NV – Consultant, Grant/Research Support, Speakers Bureau. Genentech – Consultant, Grant/Research Support, Speakers Bureau. Gilde Healthcare – Consultant. Gilead Sciences – Consultant, Grant/Research Support, Speakers Bureau. GlaxoSmithKline – Consultant, Grant/Research Support, Speakers Bureau. Innomar – Consultant. JAMP – Consultant. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. Merck – Consultant, Grant/Research Support, Speakers Bureau. Metacrine – Consultant, Grant/Research Support, Speakers Bureau. Mylan – Consultant, Grant/Research Support, Speakers Bureau. Pandion Therapeutics – Consultant, Grant/Research Support, Speakers Bureau. Pendopharm – Consultant, Grant/Research Support, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. Prometheus Therapeutics and Diagnostics – Consultant, Grant/Research Support, Speakers Bureau. Protagonist Therapeutics – Consultant, Grant/Research Support, Speakers Bureau. Reistone Biopharma – Consultant, Grant/Research Support, Speakers Bureau. Roche – Consultant, Grant/Research Support, Speakers Bureau. Roivant – Consultant. Sandoz – Consultant, Grant/Research Support, Speakers Bureau. Second Genome – Consultant, Grant/Research Support, Speakers Bureau. Shire – Speakers Bureau. Sorriso Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Syndegen – Consultant. Takeda – Consultant, Intellectual Property/Patents, Speakers Bureau. TD Securities – Consultant. Teva – Consultant, Grant/Research Support, Speakers Bureau. Topivert – Consultant, Grant/Research Support, Speakers Bureau. Ventyx Biosciences – Consultant, Grant/Research Support, Speakers Bureau. Vividion Therapeutics – Consultant, Grant/Research Support, Speakers Bureau.

Walter Reinisch, MD, PhD¹, David Štěpek, MD², Radoslaw Kempinski, MD, PhD³, Silvio Danese, MD, PhD⁴, Bruce E. Sands, MD, MS, FACG⁵, Bogdan Ratiu-Duma, ⁶, Rajendra Singh, PhD⁷, Hadas Barkay, PhD⁸, Gordon Raphael, MD⁹, Vipul Jairath, MBChB, DPhil, MRCP¹⁰. P5324 - Duvakitug, an anti-TL1a mAb, Demonstrates Efficacy and Favorable Safety as an Induction Treatment in Adults With Moderately to Severely Active Ulcerative Colitis: Results From the RELIEVE UCCD Phase 2b Basket Trial, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.