First and Only Ulcerative Colitis Treat-to-Target Trial Shows Treating to Disease Clearance vs. Symptomatic Remission with ENTYVIO® (vedolizumab) Prolongs Time to First Disease-Related Complication

• More than half of ENTYVIO patients who met their assigned treatment target reached disease clearance (composite of corticosteroid-free symptomatic, endoscopic and histologic remission) at Week 16
• VERDICT is the first trial to provide macroscopic and microscopic evidence of intestinal tissue repair associated with disease clearance in largely bio-naïve patients treated with an advanced therapy​

OSAKA, Japan & CAMBRIDGE, Mass. — Takeda ( TSE:4502/NYSE:TAK) announced new data from VERDICT ( NCT04259138), showing that treating adults with intravenous ENTYVIO^® (vedolizumab) to achieve corticosteroid-free (CSF) disease clearance versus CSF symptomatic remission alone, resulted in a significantly longer time to first ulcerative colitis (UC)-related complication (hazard ratio 0.33 [95% confidence interval 0.17-0.67]; P=0.0014), reducing UC complication risk by nearly 70 percent. VERDICT, a Phase 4 ENTYVIO clinical trial, provides the first prospective, randomized evidence that disease clearance is an achievable and clinically relevant target in the treatment of moderate to severe ulcerative colitis.¹ Results were presented during late-breaker and poster sessions at United European Gastroenterology (UEG) Week 2026 and published in the United European Gastroenterology Journal.

“There has been increasing conversation about whether achieving deeper levels of remission – addressing both visible and microscopic inflammation – ameliorates the burden of ulcerative colitis in the long-term,” said Vipul Jairath MBChB, DPhil, FRCP, FRCPC, Professor of Medicine at Western University, Alimentiv chief medical officer and lead study author. “VERDICT suggests that implementation of a treat-to-target strategy can change the disease course. It also expands the body of evidence for treating with ENTYVIO, with the goal of achieving deeper and durable disease control within 16 weeks.”

“For people living with UC, symptom relief does not always tell the full story of what is happening beneath the surface. Achieving deep healing and disease control without corticosteroids is an important goal of treatment. The VERDICT data further support the strength of gut-focused ENTYVIO in achieving outcomes such as disease clearance – within 16 weeks of treatment initiation – while also adding new molecular and cellular evidence suggesting restoration of gut function in bio-naïve patients,” said Vijay Yajnik, Vice President, Global Medical Affairs, GI & Inflammation at Takeda. “VERDICT reflects our commitment to generating evidence that aims to answer some of the most complex questions in ulcerative colitis treatment strategies and standards of care.”

VERDICT randomized adults with moderate to severe ulcerative colitis to three increasingly stringent CSF treatment targets (Group 1: symptomatic remission; Group 2: symptomatic + endoscopic remission; and Group 3: symptomatic + endoscopic + histologic remission, or disease clearance) to assess whether deeper levels of remission were associated with longer time to UC-related complications. Treatment was escalated based on assigned targets using ENTYVIO-based algorithms, which may have included an increase in dose frequency. The study’s primary outcome compared time to first UC-related complication (hospitalization, colectomy, use of rescue therapy, treatment-related, and other UC-related complications) between groups 3 and 1 up to 80 weeks after target achievement. Among the achieved-target population, key findings include:

• After treatment with ENTYVIO, nearly 60% (400/672) of randomized patients achieved their assigned CSF target by Week 48 (Group 1: 137 [74.1%]; Group 2: 125 [56.3%]; Group 3: 138 [52.1%])
• The primary endpoint was met with the disease-clearance group (Group 3) experiencing a longer time to first UC-related complication than the symptomatic-remission group (HR 0.33; 95% CI, 0.17–0.67; P=0.0014)
• Treating to stringent composite targets (disease clearance) with ENTYVIO reduced UC complication risk by ~70%, up to 80 weeks after target achievement
• Among patients achieving the CSF symptomatic + endoscopic remission target (Group 2), more than 80% also achieved histologic remission at Week 48
• Time to UC-related complication was similar between patients in groups 2 and 3 (1.10 [0.45-2.69] P=0.8023)
• 51 UC-related complications occurred, with use of rescue therapy being the most frequent
• Adverse event rates were similar across groups and unaffected by treatment escalation and more frequent ENTYVIO dosing to achieve more stringent targets

The safety profile observed throughout 96 weeks was generally consistent with previously reported data, with no new safety signals identified. The most common adverse events (≥5%) were ulcerative colitis, anaemia, haematochezia, COVID-19 infection, influenza, nasopharyngitis and arthralgia.¹ Additional analyses from VERDICT also presented at UEG Week explored molecular changes associated with early disease clearance.^2,3 Proteomic and transcriptomic analyses identified distinct molecular patterns among bio-naïve patients who achieved disease clearance by Week 16, including changes in pathways related to inflammation, mucosal homeostasis and tissue repair. These exploratory findings may contribute to a better understanding of the biology associated with disease clearance and warrant further investigation.

The impact of ulcerative colitis can extend well beyond day-to-day symptoms.⁴ Over time, up to 30 percent of patients may experience complications, including painful flares, hospitalization and surgery, that can disrupt their lives and take an emotional and financial toll.^5,6 This underscores the importance of addressing not only symptoms but also facilitating gut healing with the goal of changing the course of disease to minimize long-term impact and improve outcomes.

Disease clearance is a treatment target that combines three levels of remission: corticosteroid-free (CSF) symptomatic remission (no symptoms without steroids), endoscopic remission (visible healing of the gut lining), and histologic remission (healing at the microscopic level).

It is a deeper standard than symptom relief alone and proposed by the International Organisation for the Study of Inflammatory Bowel Diseases (IOIBD) as having potential to reduce the risk of disease recurrence and progression in the long term. VERDICT is the first randomized trial in UC to include this stringent treatment target in a prespecified hypothesis.

The VERDICT trial (

) is a Phase 4 ENTYVIO randomized trial, the first and only prospective trial in UC to assess the optimal treatment target to prolong time to ulcerative colitis (UC)-related complications.

The study found that treating adults with moderate to severe ulcerative colitis to a corticosteroid-free (CSF) disease clearance target with ENTYVIO lengthened the time to first UC-related complication, compared with treating to CSF symptomatic remission alone. VERDICT is the first randomized trial in UC to include this stringent treatment target in a prespecified hypothesis. Additionally, among those who achieved their treatment target, disease clearance was reached by more than half (57%) of ENTYVIO-treated patients at Week 16.

Treat-to-target means actively monitoring a patient’s disease and adjusting treatment on a set schedule until a specific, pre-defined clinical target is reached, rather than evaluating the clinical status of the patient out of the framework of an assigned target.

In VERDICT, patients were assessed for target achievement at Weeks 16 and 32 and had treatment adjusted according to a pre-established algorithm if assigned treatment target was not achieved. The achieved-target population for VERDICT included patients who reached their assigned targets at Weeks 16, 32 or 48.

The safety profile observed through 96 weeks in VERDICT was generally consistent with previously reported ENTYVIO data, with no new safety signals identified.

ENTYVIO, a biologic therapy, is the only gut-focused treatment available for ulcerative colitis and Crohn’s disease in adults. It specifically binds to the α4β7 integrin and blocks its interaction with MAdCAM-1, which is mainly expressed on the gut endothelial cells.

ENTYVIO is approved for IV and subcutaneous (SC) administration in adults with moderately to severely active ulcerative colitis and Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist (approvals vary by market).

Marketing authorization has been granted in more than 80 countries for ENTYVIO IV and in more than 50 countries for ENTYVIO SC. Globally, ENTYVIO IV and SC have more than 2.3 million patient years of exposure to date.

VERDICT (

) is a Phase 4 randomized treat-to-target trial conducted by Alimentiv, in collaboration with Takeda.

VERDICT included 672 adults with active moderate to severe UC (Mayo rectal bleeding subscore [RBS]≥1; Mayo endoscopic score [MES]≥2), with most being bio-naïve and/or having severe disease (as measured by MES). Patients were randomly divided into three groups, each assigned an increasingly stringent treatment target: corticosteroid-free (CSF) symptomatic remission (Group 1); CSF symptomatic plus endoscopic remission (Group 2); and CSF symptomatic, endoscopic and histologic remission (Group 3). Treatment was escalated to assigned targets using ENTYVIO-based algorithms, which may have included an increase in dose frequency. Achievement of treatment targets was assessed at Weeks 16, 32 and 48. The study’s primary outcome compared time to first UC-related complication (hospitalization, colectomy, use of rescue therapy, treatment-related, and other UC-related complications) up to 80 weeks after target achievement between groups 3 and 1.

Please consult the ENTYVIO (Vedolizumab) Summary of Product Characteristics (SmPC) before prescribing, particularly in relation to dosing and treatment monitoring.

Entyvio should be initiated and supervised by a specialist healthcare professional experienced in diagnosis and treatment of ulcerative colitis, Crohn’s disease or pouchitis. Patients should be given the package leaflet.

include Hypersensitivity to the active substance or to any of the excipients. Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML).

The

with ENTYVIO are nasopharyngitis, headache, arthralgia, pneumonia, Clostridium difficile infection, bronchitis, gastroenteritis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, Herpes Zoster, paraesthesia, hypertension, oropharyngeal pain, nasal congestion, cough, anal abscess, anal fissure, nausea, dyspepsia, constipation, abdominal distension, flatulence, haemorrhoids, rectal haemorrhage, liver enzyme increased, rash, pruritus, eczema, erythema, night sweats, acne, muscle spasms, back pain, muscular weakness, fatigue, pain in the extremity, pyrexia, injection site reaction.

No clinically relevant differences in the overall safety profile and adverse reactions were observed in patients who received subcutaneous vedolizumab compared to the safety profile observed in clinical studies with intravenous vedolizumab with the exception of injection site reactions.

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Data on file. Takeda Pharmaceuticals.

Contacts

Christopher O’Reilly

Tsuyoshi Tada (Tokyo)