Introduction

Tamuzimod is a novel, oral, selective sphingosine-1-phosphate-1 receptor modulator in development for the treatment of ulcerative colitis (UC). The efficacy and safety of tamuzimod as induction therapy was previously demonstrated in a phase 2, multicentre, randomised, double-blind, placebo-controlled trial (NCT05156125).¹Here we report 52-week maintenance data from the long-term extension (LTE) treatment period of that trial.

Aims & Methods

Adults (N=213) with a modified Mayo score of 4-9 and inadequate/loss of response/intolerance to at least one approved UC therapy were randomised 1:1:1 to once-daily treatment with oral tamuzimod (30 mg or 60 mg) or placebo for 13 weeks. Patients who completed the 13-week induction treatment period and achieved clinical response were eligible for the LTE treatment period and once daily blinded maintenance therapy with their previously assigned treatment for up to 39 weeks. Clinical, endoscopic, and histologic outcomes (defined in Table) were evaluated at week 52. Adverse events (AEs) and laboratory abnormalities were also assessed for safety.

Results

Of 203 patients who completed week 13, 85 were eligible and entered the LTE treatment period (22/66 placebo, 34/70 tamuzimod 30 mg, 29/67 tamuzimod 60 mg). At week 52, clinical remission occurred in 50.0% of patients who received maintenance treatment with either tamuzimod 30 mg (16/32) or 60 mg (14/28) compared to 18.2% (4/22) of patients who received placebo. Endoscopic remission occurred in 43.8% (14/32) and 46.4% (13/28) of patients who received tamuzimod 30 mg and 60 mg, respectively, compared to 18.2% (4/22) of patients who received placebo. Higher rates of sustained (week 13 and week 52) clinical remission, symptomatic remission, endoscopic improvement, and the composite outcomes of endoscopic and clinical or histologic remission, and endoscopic improvement and histologic remission were also observed with both tamuzimod doses compared to placebo (see Table). Consistent with these efficacy outcomes and tamuzimod’s proposed mechanism of action, absolute lymphocyte count (ALC) was relatively unchanged from baseline in patients who received placebo, whereas sustained reductions in ALC were observed for both tamuzimod doses over time, with a 58.9% and 71.5% decrease in ALC from baseline observed at week 52 for patients who received tamuzimod 30 mg and 60 mg, respectively. No new safety signals were identified during the LTE treatment period. No instances of bradycardia, atrioventricular block, serious infections, or macular oedema were observed, and no deaths occurred.

Table. Efficacy Outcomes at Week 52

Conclusion

Maintenance treatment with both 30 mg and 60 mg tamuzimod was efficacious and well-tolerated for up to 52 weeks. High rates of both clinical and endoscopic remission observed during tamuzimod induction and maintenance therapy may be potentially due to rapid and sustained ALC reductions. Efficacy and safety data from this LTE treatment period support the continued clinical development of tamuzimod for treatment of UC.

References

1. Sands BE, Panaccione R, D'Haens G, et al. Efficacy and safety of the oral selective sphingosine-1-phosphate-1 receptor modulator VTX002 in moderately to severely active ulcerative colitis: Results from a randomized, double-blind, placebo-controlled, phase 2 trial. Gastroenterology 2024; 166: S-240. DOI: https://doi.org/10.1016/S0016-5085(24)01036-9.

Disclosure

SD: consulting for AbbVie,Alimentiv,Allergan,Amgen,Applied Molecular Transport,AstraZeneca,Athos Therapeutics,Biogen,Boehringer Ingelheim,Bristol Myers Squibb,Celgene,Celltrion,DrFalk Pharma,Eli Lilly,Enthera,Ferring,Gilead,Hospira,Inotrem,Janssen,J&J,Morphic,MSD,Mundipharma,Mylan,Pfizer,Roche,Sandoz,Sublimity Therapeutics,Takeda,Teladoc Health,TiGenix,UCB,Vial,Vifor; lecture fees from Abbvie,Amgen,Ferring,Gilead,Janssen,Mylan,Pfizer,Takeda.
RP: consulting for Abbott,AbbVie,Abbivax,Alimentiv,Amgen,AnaptysBio,Arena Pharmaceuticals,AstraZeneca,Biogen,Boehringer Ingelheim,Bristol-Myers Squibb,Celgene,Celltrion,Cosmos Pharmaceuticals,Eisai,Elan,Eli Lilly,Ferring,Galapagos,Fresenius Kabi,Genentech,Gilead,Glaxo-Smith Kline,JAMP Bio,Janssen,Merck,Mylan,Novartis,Oppilan Pharma,Organon,Pandion Pharma,Pendopharm,Pfizer,Progenity,Prometheus Biosciences,Protagonist Therapeutics,Roche,Sandoz,Satisfai Health,Shire,Sublimity Therapeutics,Spyre Therapeutics,Takeda,Theravance Biopharma,Trellus,Union Biopharma,Viatris,Ventyx,UCB; speaker for AbbVie,Amgen,Arena Pharmaceuticals,Bristol-MyersSquibb,Celgene,Eli Lilly,Ferring,Fresenius Kabi,Gilead,Janssen,Merck,Organon,Pfizer,Roche,Sandoz Shire,Takeda; advisory boards for: AbbVie,Alimentiv,Amgen,Arena Pharmaceuticals,AstraZeneca,Biogen,Boehringer Ingelheim,Bristol-Myers Squibb,Celgene,Eli Lilly,Ferring,Fresenius Kabi,Genentech,Gilead,Glaxo-Smith Kline,JAMP Bio,Janssen,Merck,Mylan,Novartis,Oppilan Pharma Organon,Pandion Pharma,Pfizer,Progenity,Protagonist Therapeutics,Roche,SandozShire,Sublimity Therapeutics,Takeda,Ventyx. GRD: advisor fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, GlaxoSmithKline, Pfizer Inc, Johnson and Johnson, Takeda Pharmaceutical Company, Prometheus Biosciences, and Ventyx Biopharma. SS: Personal fees were received from Abbvie, Amgen, Arena, Biogen, Bristol Meyers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Lilly, Morphic, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance, Ventyx. VJ: consulting/advisory board for AbbVie,Alimentiv,Arena pharmaceuticals,Asahi Kasei Pharma,Asieris,Astra Zeneca,Avoro Capital,Bristol Myers Squibb,Celltrion,Eli Lilly,Endpoint Health,Enthera,Ferring,Flagship Pioneering,Fresenius Kabi,Galapagos,Gilde Healthcare,GlaxoSmithKline,Genentech,Gilead,Innomar,JAMP,Janssen,Merck,Metacrine,Mylan,MRM Health,Pandion,Pendopharm,Pfizer,Protagonist,Prometheus Biosciences,Reistone Biopharma,Roche,Roivant,Sandoz,Second Genome,Sorriso,Synedgen,Takeda,TD Securities,Teva,Topivert,Ventyx,Vividion; speaker for Abbvie,Ferring,Bristol Myers Squibb,Galapagos,Janssen Pfizer Shire,Takeda,Fresenius Kabi. AD: nothing to disclose. JK: consulting/speaker/ advisory board for Lilly,BMS,Nestle,and Danon. SN, KG, BL: employees of Ventyx Biosciences. WJS: consulting for Alimentiv and Shoreline Biosciences; stock/stock options from Prometheus Biosciences,Prometheus Laboratories,Shoreline Biosciences,Ventyx,Mirador Therapeutics; employee at Ventyx and Mirador Therapeutics; serving on the Board of Directors at Prometheus Laboratories. SV: financial research support from AbbVie,J&J,Pfizer,Takeda and Galapagos; speaker/consulting fees from AbbVie,Abivax,AbolerlsPharma,AgomAb,Alimentiv,Arena Pharmaceuticals,Astrazeneca,BioraTherapeutics,BMS,Boehringer Ingelheim,Celgene,Cytoki Pharma,Dr Falk Pharma,Ferring,Galapagos,Genentech Roche,Gilead,GSK,Hospira,lmidomics,Janssen,J&J,Lilly,Materia Prima,Mestag Therapeutics,Microbiotica,MiroBio,Morphic,MrMHealth,Mundipharma,MSD,Pfizer,Prodigest,Progenity,Prometheus,Robarts Clinical Trials,Surrozen,Takeda,Theravance,Tillots Pharma AG,VectivBio,Ventyx,and Zealand Pharma. DTR: grants from Takeda; consulting for Abbvie,Altrubio,Apex,Avalo Therapeutics,Bristol-Myers Squibb,Buhlmann Diagnostics Corp,Celgene,Connect BioPharma,Intouch Group,Iterative Health,Janssen Pharmaceuticals,Lilly,Pfizer,Samsung Neurologica,and Takeda; serving on Board of Trustees for Crohn’s & Colitis Foundation and Board of Directors for Cornerstones Health. LP: consulting for Abbvie,Abivax,Adacyte,Alimentiv,Amgen,Applied Molecular Transport,Arena,Banook,Biogen,BMS,Celltrion,Connect Biopharm,Cytoki Pharma,Enthera,Ferring,Fresenius Kabi,Galapagos,Genentech,Gilead,Gossamer Bio,GSK,IAC Image Analysis,Index Pharmaceuticals,Inotrem,Janssen,Lilly,Medac,Mopac,Morphic,MSD,Nordic Pharma,Novartis,Oncodesign Precision Medicine,ONO Pharma,OSE Immunotherapeuthics,Pandion Therapeuthics,Par' Immune,Pfizer,Prometheus,Protagonist,Roche,Samsung,Sandoz,Sanofi,Satisfay,Takeda,Telavant,Theravance,Thermo Fischer,Tigenix,Tillots,Viatris,Vectivbio,Ventyx,Ysopia; grants from Celltrion,Fresenius Kabi,Medac,MSD,Takeda; lecture fees from Abbvie,Amgen,Arena,Biogen,Celltrion,Ferring,Galapagos,Genentech,Gilead,Janssen,Lilly,Medac,MSD,Nordic Pharma,Pfizer,Sandoz,Takeda,Tillots,Viatris. BES: non-financial support/personal fees/stock/stock options from Ventyx Biosciences during the conduct of the study; grant/personal fees/non-financial support from AbbVie,Abivax,Adiso Therapeutics,Agomab,Alimentiv,Amgen,AnaptysBio,Arena Pharmaceuticals,Artugen Pharmaceuticals,AstraZeneca,Biora Therapeutics,Boehringer Ingelheim,Boston Pharmaceuticals,Bristol Myers Squibb,Calibr,Celgene,Celltrion,ClostraBio,Equilium,Enthera,Evommune,Ferring,Fresenius Kabi,Galapagos,Genentech,Gilead Sciences,Glaxo SmithKline,GossamerBio,Index Pharmaceuticals,Innovation Pharmaceuticals,Inotrem,Janssen,J&J,Kalleido,Kallyope,Lilly,Merck,Microbiotica,Mobius Care,Morphic Therapeutics,MRM Health,Nexus Therapeutics,Immunyx Therapeutics,Nimbus Discovery,Odyssey Therapeutics,Pfizer,Progenity,Prometheus Biosciences,Prometheus Laboratories,Protagonist Therapeutics,Q32 Bio,Rasayana Therapeutics,Recludix Therapeutics,Reistone Biotherapeutics,Sun Pharma,Surrozen,Target RWE,Takeda,Teva,Theravance Biopharma,TLL Pharmaceutical,TR1X,Union Therapeutics,Palisade Bio, outside submitted work.

Introduction

Gastroesophageal reflux disease (GERD) is a common disorder characterized by the backward flow of stomach contents into the esophagus, impacting millions globally and significantly reducing quality of life. Typical symptoms include heartburn and acid reflux, while atypical presentations may involve noncardiac chest pain, chronic cough, and laryngitis(1).Over the past decade (2010–2021), GERD incidence and prevalence have risen sharply in Europe compared to global trends, leading to increased disability-adjusted life years (DALYs). Its multifactorial pathogenesis—driven by chemical, mechanical, psychological, and neurological mechanisms—affects symptom severity, diagnosis, and therapeutic outcomes(2).

Aims & Methods

This study aims to investigate the escalating burden of Gastroesophageal Reflux Disease (GERD) in Europe from 2010 to 2021, comparing its incidence, prevalence, and disability-adjusted life years (DALYs) with global trends to evaluate current healthcare policies and highlight the need for streamlined, evidence-based interventions that address regional disparities in disease burden. The findings will support policy refinement, ensuring healthcare systems are equipped with effective prevention strategies, optimized treatment protocols, and equitable resource allocation to reduce GERD’s long-term impact on patient health and healthcare infrastructure.
Incidence, Prevalence and disability-adjusted life years (DALYs) were calculated using the Global Burden of Disease (GBD) Database 2021. Joinpoint regression was used to calculate annual percentage changes (APCs) in ASDR, DALYs, and YLL with 95% uncertainty intervals, and significant trends over time were identified. Statistical significance was set at a p-value of <0.05

Results

Globally, GERD-related DALYs increased from 72.24 per 100,000 (95% CI: 36.45–128.77) in 2010 to 75.56 per 100,000 (95% CI: 38.05–133.87) in 2021. Prevalence rose from 9,398.70 per 100,000 (95% CI: 8,342.02–10,517.59) in 2010 to 9,838.60 per 100,000 (95% CI: 8,732.46–11,056.05) in 2021, while incidence climbed from 3,717.75 per 100,000 (95% CI: 3,298.17–4,113.24) in 2010 to 3,881.86 per 100,000 (95% CI: 3,445.56–4,299.95) in 2021.
Europe saw GERD-related DALYs rise from 75.38 per 100,000 (95% CI: 37.98–133.77) in 2010 to 77.57 per 100,000 (95% CI: 39.13–137.23) in 2021. Prevalence increased to 10,091.72 per 100,000 (95% CI: 8,938.24–11,206.79), and incidence reached 3,978.62 per 100,000 (95% CI: 3,521.81–4,418.93) in 2021.
Eastern Europe consistently showed the highest GERD burden, followed by Central Europe, while Western Europe had the lowest figures.

• Eastern Europe: 88.73 DALYs per 100,000 (95% CI: 44.67–156.85) in 2021
• Central Europe: 86.05 per 100,000 (95% CI: 43.45–152.64)
• Western Europe: 63.30 per 100,000 (95% CI: 31.76–112.67)

Conclusion

The increasing burden of Gastroesophageal Reflux Disease (GERD) in Europe from 2010 to 2021, particularly in Eastern Europe, highlights the need for targeted healthcare interventions. With rising incidence, prevalence, and disability-adjusted life years (DALYs), addressing lifestyle, environmental, and healthcare access disparities is essential. Streamlined policies, optimized treatment strategies, and preventive measures can help mitigate GERD’s impact, improve patient outcomes, and reduce the strain on healthcare systems.

References

1-Mahajan R, Kulkarni R, Stoopler ET. Gastroesophageal reflux disease and oral health: A narrative review. Spec Care Dentist. 2022;42(6):555-564. doi:10.1111/scd.12726
2-Sharma P, Yadlapati R. Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid. Ann N Y Acad Sci. 2021;1486(1):3-14. doi:10.1111/nyas.14501

Disclosure

No conflict of interest.