Vedolizumab is a humanized monoclonal antibody that specifically targets α4β7 integrin, a key mediator of inflammatory bowel disease (IBD). It is believed to prevent lymphocyte trafficking to the gut, without compromising systemic immunity (unlike existing IBD treatments).
Takeda has conducted two randomised, double-blind, placebo-controlled phase III trials of vedolizumab in patients with IBD.
The GEMINI I trial recruited 895 patients with moderately to severely active ulcerative colitis. GEMINI II enrolled 1,115 patients with moderately to severely active Crohn’s disease. In both cases, participants had failed to respond adequately to at least one previous conventional therapy, including TNFα antagonists.
Patients underwent a year of treatment with vedolizumab or placebo, starting with six weeks of induction therapy.
Both trials showed that vedolizumab produced significant improvements in clinical remission rates in the maintenance phase of treatment, compared with placebo. After a year of maintenance treatment, patients in GEMINI I receiving 300mg vedolizumab intravenously every 4 weeks had a corticosteroid-free remission rate of 45%, compared with 14% for those given placebo.
Clinical response rates were also increased in the induction phase of both studies, reaching significance versus placebo in GEMINI I.
Adverse events associated with vedolizumab included arthralgia, fever, nasopharyngitis, headache, nausea and abdominal pain.
"We thought that vedolizumab would be safer than systemic immunosuppression, and I think the data are consistent with that," said Brian G. Feagan, lead investigator and Professor of Medicine at Western University in Ontario, Canada, commenting on the results of GEMINI I. "This will be a first-line treatment."