Takeda KEPLER Trial: Promising Vedolizumab Results for Pediatric Ulcerative Colitis

Takeda announced positive Phase 3 KEPLER trial data for ENTYVIO (vedolizumab) in children and adolescents aged 2-17 with moderately to severely active ulcerative colitis (UC). The results, presented at the 21st European Crohn’s and Colitis Organisation (ECCO) Congress, highlight potential clinical remission benefits in a population with limited treatment options.​

Awny Farajallah, MD, Takeda’s chief medical officer, emphasized the long-standing limited options for pediatric UC families and clinicians. He described KEPLER’s encouraging results as extending ENTYVIO’s established adult benefits to children ≥2 years old, building on over a decade of data and underscoring Takeda’s leadership in IBD care for vulnerable groups.

Trial Design and Patient Population

The KEPLER study (NCT04779307; EudraCT 2020-004300-34) enrolled 120 patients aged 2-17 years with moderately to severely active UC (modified Mayo score 5-9, endoscopic subscore ≥2) who inadequately responded to conventional therapies like steroids, immunomodulators, or TNF antagonists.

All received open label IV vedolizumab induction for 14 weeks. Responders (93 patients) were randomized to weight-based low-dose (LD) or high-dose (HD) maintenance every 8 weeks: ≥30 kg (300 mg HD/150 mg LD), 15-<30 kg (200 mg HD/100 mg LD), 10-15 kg (150 mg HD/100 mg LD).​

 Key Efficacy Outcomes

Nearly half (47.3%) of randomized patients achieved the primary endpoint of clinical remission (symptomatic improvement and minimal/no endoscopic activity per modified Mayo score) at Week 54. Secondary endpoints included 34.7% clinical remission at Week 14 and 29% sustained remission at Weeks 14 and 54. These findings suggest vedolizumab’s gut-selective mechanism binding α4β7 integrin to block lymphocyte gut homing may extend effectively to pediatrics.

Safety Profile

Vedolizumab’s safety aligned with adult data, showing no new signals. Common treatment-emergent adverse events (≥10%) were upper respiratory infection (30%), UC worsening (17.5%), and pyrexia (12.5%). For full details on precautions, warnings like infusion reactions, infections, PML risk, and malignancies, refer to the Entyvio Summary of Product Characteristics (SmPC).

Ramalingam Arumugam, MD, KEPLER investigator, called UC is a life-altering for young patients with few effective treatments. He praised vedolizumab’s meaningful benefits in children/adolescents failing conventional/TNF therapies, achieving ~50% remission at one year with adult-like safety for ages 2+.

Vedolizumab stands as the only gut-selective biologic approved for ulcerative colitis and Crohn’s disease. It precisely binds to the α4β7 integrin on lymphocytes, blocking their interaction with MAdCAM-1 primarily expressed on gut endothelial cells, thereby limiting inflammation to the GI tract without broad systemic immunosuppression.

Takeda plans regulatory submissions in the US, EU, and beyond for pediatric UC approval. Currently approved for adults, vedolizumab has over 1 million patient-years exposure.

Reference

Positive Phase 3 Data Demonstrate Potential for ENTYVIO® (vedolizumab) to Address Treatment Gap for Children and Adolescents with Moderate to Severe Ulcerative Colitis, 19 February 2026, Takeda Phase 3 Study Results in Pediatric Ulcerative Colitis

A Study of Vedolizumab in Children and Teenagers with Moderate to Severe Ulcerative Colitis (UC), ClinicalTrials.gov ID NCT04779307, https://clinicaltrials.gov/study/NCT04779307

EudraCT Trial, EudraCT 2020-004300-34, Clinical Trials register – Search for 2020-004300-34

ENTYVIO Prescribing Information (SmPC), https://www.ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_en.pdf