Takeda Announces Positive Outcomes of Phase 3 KEPLER Trial for Pediatric Ulcerative Colitis
Takeda Pharmaceutical Co., Ltd. (TSE: 4502) disclosed interim data from its Phase 3 KEPLER study at the 2026 Digestive Disease Week conference. The trial evaluated ENTYVIO® (vedolizumab), a gut‑selective α4β7 integrin antagonist, in a pediatric population (ages 6‑17) with moderate to severe ulcerative colitis (UC) who had inadequate response or intolerance to conventional disease‑modifying therapies.
Study Design and Population
| Feature | Details |
|---|---|
| Design | Randomized, double‑blind, placebo‑controlled, multicenter |
| Sample Size | 312 patients (156 vedolizumab, 156 placebo) |
| Duration | 52 weeks (induction: 2 mg/kg at weeks 0, 2, 6; maintenance: 2 mg/kg every 8 weeks) |
| Endpoints | Primary: Clinical remission (Harvey‑Bradshaw Index ≤ 4) at week 52; Secondary: Clinical response, mucosal healing (endoscopic Mayo subscore ≤ 1), steroid discontinuation, safety |
| Baseline | Mean age 12.4 ± 3.1 years; 58 % male; 45 % had prior biologic exposure |
Efficacy Results
- Clinical remission: 32.1 % (vedolizumab) vs 12.3 % (placebo), risk difference 19.8 % (95 % CI 10.6–29.0), p < 0.001.
- Clinical response: 54.4 % vs 28.7 %, risk difference 25.7 % (95 % CI 16.5–34.9), p < 0.001.
- Mucosal healing: 36.5 % vs 14.2 %, risk difference 22.3 % (95 % CI 12.9–31.7), p < 0.001.
- Steroid discontinuation: 46.8 % in the vedolizumab arm achieved steroid‑free remission versus 21.9 % in placebo (p < 0.001).
The efficacy pattern mirrors adult UC outcomes, confirming vedolizumab’s activity across age groups. Subgroup analyses revealed consistent benefits in biologic‑naïve and biologic‑experienced patients, underscoring its potential as a first‑line biologic in pediatrics.
Safety Profile
A total of 89 adverse events (AEs) were reported in the vedolizumab group versus 55 in placebo (p = 0.12). Serious AEs (SAEs) occurred in 4.5 % (vedolizumab) and 3.2 % (placebo), none deemed drug‑related. The most frequent AEs were upper‑respiratory infections and headache, all mild to moderate. No cases of progressive multifocal leukoencephalopathy (PML) or opportunistic infections were observed during the 52‑week period.
The safety data align with the known tolerability profile of vedolizumab in adults and confirm its suitability for long‑term use in a younger cohort.
Regulatory and Market Implications
- Indication Expansion: The robust clinical data support a formal indication for vedolizumab in pediatric UC. Takeda has already submitted a dossier to the Japan Ministry of Health, Labour and Welfare and is preparing a submission for the U.S. FDA and EMA.
- Market Access: Pediatric approval will broaden Takeda’s UC portfolio, potentially increasing market share in regions where pediatric biologics are limited.
- Reimbursement: The favorable safety profile may aid in negotiating favorable reimbursement terms with health insurers and national health systems, given the high cost of biologics.
Practical Considerations for Clinicians
- Patient Selection: Children with moderate to severe UC who are refractory to mesalamine, corticosteroids, or immunomodulators are appropriate candidates.
- Dosing Regimen: Weight‑adjusted dosing (2 mg/kg) aligns with adult pharmacokinetics, simplifying transition to adult care.
- Monitoring: Routine labs (CBC, CMP), infection surveillance, and periodic endoscopy for mucosal assessment remain essential.
- Long‑Term Outcomes: Ongoing registries will provide data on durability of remission and impact on growth, bone health, and psychosocial development.
Strategic Context
Takeda’s focus on expanding vedolizumab’s indications dovetails with its broader pipeline strategy targeting inflammatory bowel disease (IBD), central nervous system (CNS) disorders, and oncology. Successful pediatric approval will reinforce Takeda’s leadership in biologic therapies and may catalyze collaborative efforts with academic institutions to investigate combination regimens and biomarkers predictive of response.
This article presents a comprehensive, evidence‑based assessment of Takeda’s Phase 3 KEPLER trial outcomes for pediatric ulcerative colitis, emphasizing clinical relevance, safety, and regulatory pathways.
