Ulcerative Colitis (Pediatric)

October 30, 2017

Celgene released positive phase II data of ozanimod for ulcerative colitis. TOUCHSTONE was a phase II, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of ozanimod (RPC1063) with placebo in patients with moderately to severely active ulcerative colitis. A total of 197 patients were randomized and treated once daily with 1mg ozanimod (n=67), 0.5mg ozanimod (n=65) or placebo (n=65) for eight weeks (the induction phase). The primary endpoint was the proportion of patients in remission (Mayo score ≤2, no subscore >1) at week eight. Secondary endpoints were the proportion of patients achieving clinical response (reduction in Mayo score of ≥3 and ≥30% with a decrease in the rectal bleeding score of ≥1 or a rectal bleeding score ≤1), proportion of patients with mucosal improvement (endoscopy score ≤1) and the change in Mayo score. Safety assessments included ECG testing, pulmonary function testing, optical coherence tomography and adverse events. At week 92, of the 100 patients who underwent efficacy evaluations, 91% had little or no active disease based on the physician global assessment (PGA 0 or 1), 97% had little or no blood in their stools (rectal bleeding subscore [RBS] 0 or 1) and 86% had no blood in the stools (RBS 0). The safety profile at week 92 was similar to that reported in the placebo-controlled portion of the study. The most common AEs were UC flare, anemia, upper respiratory tract infection and back pain. The only SAEs in two or more patients were anemia and UC flare.

October 3, 2016

Takeda Pharmaceutical reported results of a multicenter, phase III, randomized, placebo-controlled trial of Entyvio (vedolizumab) therapy in patients with ulcerative colitis (UC). As part of the eligibility criteria for GEMINI 1, patients had demonstrated, within the previous five-year period, an inadequate response to, loss of response to or intolerance of one of the following therapies: corticosteroids (outside the U.S. only), immunosuppressives (azathioprine or mercaptopurine) and/or infliximab, as this was the only TNF antagonist approved for the treatment of UC at the time of enrollment. GEMINI 1 enrolled 464 patients without prior TNF antagonist therapy (TNF-naïve) and 367 who had failed therapy because of inadequate response, loss of response or intolerance (TNF-failure). Investigators found greater absolute differences between vedolizumab and placebo for TNF-naïve patients than for TNF-failure patients at week six and the risk ratios (RRs) were similar. Week six response rates with vedolizumab and placebo were 53.1% and 26.3%, respectively, in TNF-naïve patients (AD: 26.4%; 95% confidence interval [CI]: 12.4, 40.4; RR: 2.0; 95% CI: 1.3, 3.0) and 39.0% and 20.6%, respectively, in TNF-failure patients (AD: 18.1%; 95% CI: 2.8, 33.5; RR: 1.9; 95% CI: 1.1, 3.2). During maintenance, the absolute differences were similar and the RRs were higher for TNF-failure patients for most outcomes. Week 52 remission rates with vedolizumab and placebo were 46.9% and 19.0%, respectively, in TNF-naïve patients (AD: 28.0%; 95% CI: 14.9, 41.1; RR: 2.5; 95% CI: 1.5, 4.0) and 36.1% and 5.3%, respectively, in TNF-failure patients (AD: 29.5%; 95% CI: 12.8, 46.1; RR: 6.6; 95% CI: 1.7, 26.5). Vedolizumab was approved as a gut-selective humanized monoclonal antibody in the European Union. Entyvio was also approved in the U.S. in 2014.