Positive Phase 3 Data Demonstrate Potential for ENTYVIO® (vedolizumab) to Address Treatment Gap for Children and Adolescents with Moderate to Severe Ulcerative Colitis
Takeda today announced positive data from the pivotal Phase 3 KEPLER trial, which demonstrated that ENTYVIO® (vedolizumab) can offer the possibility of clinical remission for patients ages 2 and older with moderately to severely active ulcerative colitis (UC), a chronic inflammatory disease of the gastrointestinal tract and one of the two most common types of inflammatory bowel disease.1,2 The results,
presented at the 21st Congress of the European Crohn’s and Colitis Organisation (ECCO), show vedolizumab’s promising efficacy and safety profile in a patient population where therapy options remain limited.With KEPLER, Takeda is continuing to generate deeper scientific insights and identify additional patient populations who may benefit from vedolizumab, a cornerstone therapy for adults with ulcerative colitis. Vedolizumab is marketed under the trade name ENTYVIO®*.
Ulcerative colitis is a life-altering diagnosis for young patients and their families, often leaving them searching for effective options. In the KEPLER study, we observed clinically meaningful improvements with vedolizumab in an especially difficult-to-treat patient population—children and adolescents who had failed on the current standard of care, including conventional therapies and/or tumor necrosis factor (TNF) antagonists,” said Ramalingam Arumugam, MD, study investigator and pediatric gastroenterologist at MNGI Digestive Health in Minnesota. “Study data showed nearly half of patients were in remission after one year and safety was generally consistent with vedolizumab’s profile in adults, suggesting that vedolizumab could become important in addressing pediatric UC in those 2 years of age and older.
The KEPLER Phase 3 study included 120 children and adolescents 2 to 17 years-old with moderately to severely active UC who had an inadequate response to conventional treatments (such as steroids and immunomodulators) and/or tumor necrosis factor (TNF) antagonists. Study participants received open-label intravenous (IV) vedolizumab during a 14 week open-label induction period.1 Ninety-three (93) of 120 patients who achieved a clinical response at Week 14 were then randomized to low dose (n=47) or high dose (n=46) maintenance therapy with vedolizumab every 8 weeks. Of these 93 patients:
- Nearly half (47.3%) of participants achieved the primary endpoint of clinical remission at Week 54;
- More than one-third (34.7%) of patients achieved clinical remission at 14 weeks (secondary endpoint); and
- Greater than 1 in 4 (29%) participants attained the secondary endpoint of sustained clinical remission at both Weeks 14 and 54.
- Additionally, the safety profile of vedolizumab in trial participants was generally consistent with its established safety profile in adults, with no new safety signals identified.1 The most frequently occurring treatment-emergent adverse events (≥10%) reported with vedolizumab in the KEPLER study were upper respiratory infection (30%), ulcerative colitis (disease worsening) (17.5%), and pyrexia (12.5%).3
For too long, families and clinicians caring for children and adolescents with ulcerative colitis have had limited therapeutic options,” said Awny Farajallah, MD, chief medical officer of Takeda. “The Phase 3 KEPLER results are encouraging and suggest that ENTYVIO, a therapy with a well-established role in the treatment of ulcerative colitis, may offer a meaningful benefit for patients as young as two years old. These findings build on more than a decade of scientific study demonstrating the safety and efficacy of ENTYVIO and reflect Takeda’s continued leadership in advancing evidence-based care across the full spectrum of inflammatory bowel disease. Importantly, this study underscores our commitment to supporting some of the most vulnerable patient populations in gastroenterology.
Takeda plans to submit marketing applications in the United States, the European Union and other markets for intravenous ENTYVIO for the treatment of moderately to severely active ulcerative colitis in children and adolescents ages 2-17.
About the Phase 3 KEPLER Study
KEPLER is a Phase 3, global, randomized, double-blind, multi-center study to evaluate the efficacy and safety of vedolizumab IV in patients ages 2 to 17 with moderately to severely active ulcerative colitis (modified Mayo score of 5-9 with endoscopic subscore ≥2) with inadequate response to conventional therapy, such as steroids, immunomodulators, and/or tumor necrosis factor (TNF) antagonists.4,1 The study included a 14-week open-label induction period—all participants received IV vedolizumab—followed by a 40-week, randomized, double-blind maintenance period comparing two dose levels: low dose (LD) and high dose (HD). Ninety-three (93) participants were randomized to LD (n=47) or HD (n=46) arms, according to patient weight:
- Participants ≥30 kg: vedolizumab 300 mg (HD) or 150 mg (LD)
- Participants >15 to <30 kg: vedolizumab 200 mg (HD) or 100 mg (LD)
- Participants 10 to 15 kg: vedolizumab 150 mg (HD) or 100 mg (LD)
The primary endpoint was clinical remission at Week 54 in patients who achieved clinical response following open-label vedolizumab IV induction, defined here by symptomatic improvement and endoscopic evidence of no or minimal disease activity (modified Mayo Score).4 Secondary outcome measures included safety and tolerability across induction and maintenance, sustained clinical remission (clinical remission at Weeks 14 and 54), endoscopic outcomes, the impact of dose escalation for loss of response, and long-term safety and disease control assessed in follow-up periods.
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