Takeda Pharmaceutical Company Limited (Takeda), a research-based global company, announced that results from two phase 3 studies evaluating vedolizumab, an investigational humanized monoclonal antibody, for the treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD). These results were published in the August 22, 2013 issue of the New England Journal of Medicine (NEJM).

Chronic and debilitating diseases, CD and UC are the two most common types of inflammatory bowel disease (IBD) and affect more than four million people worldwide,including approximately 1.4 million Americans and 2.2 million Europeans. Vedolizumab is designed to specifically antagonize the alpha4beta7 (a4ß7) integrin, which is expressed on a subset of circulating white blood cells that have been shown to play a role in mediating the inflammatory process in CD and UC.

“The publication of these study findings is important since the results support the potential for vedolizumab, if approved, to help manage symptoms in some patients for whom certain previous treatments have failed,” said Brian Feagan, professor of medicine, epidemiology, and biostatistics at the University of Western Ontario, Canada and GEMINI lead investigator. “The data from the GEMINI programme suggest that vedolizumab may provide people living with CD and UC an additional option for inducing and maintaining clinical remission.”

In the publication, study results from GEMINI I, a placebo-controlled induction and maintenance study in patients with UC, showed that vedolizumab met primary endpoints of improvement in clinical response (reduction in the Mayo Clinic score of =3 points and =30 per cent from baseline, along with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1) at six weeks and clinical remission (Mayo score of 2 or lower and no subscore higher than 1) at 52 weeks. In addition, a significantly greater proportion of patients receiving vedolizumab achieved mucosal healing (Mayo endoscopic subscore of 0 or 1) at six and 52 weeks, and glucocorticoid-free remission at 52 weeks, compared with placebo.15 Discussed in a separate publication, results from GEMINI II, a placebo-controlled induction and maintenance study in patients with CD, showed that vedolizumab demonstrated statistically significant improvement in the primary endpoint of clinical remission (Crohn’s disease activity index [CDAI] score =150 points) at six weeks and at 52 weeks compared to placebo. At six weeks, no significant difference was observed in the co-primary endpoint of CDAI-100 response (=100-point decrease in the CDAI score) between the vedolizumab and placebo groups. A significantly greater proportion of patients showed CDAI-100 response and glucocorticoid-free remission at 52 weeks.

GEMINI I and GEMINI II are part of the four-study GEMINI Studies™, studying vedolizumab in 2,700 patients in nearly 40 countries, making it the largest phase 3 clinical trial programme conducted to date simultaneously evaluating both CD and UC. Enrolled patients had failed at least one conventional therapy, including glucocorticoids, immunomodulators and/or a tumor necrosis factor-alpha (TNF-a) antagonist. TNF-a antagonist failure patients included those with inadequate response (primary non-responders), loss of response (secondary non-responders) or those who were intolerant.

“These clinical studies suggest that vedolizumab may have the potential to maintain clinical remission in the appropriate patients,” said Asit Parikh, vice president, general medicine, Takeda. “Takeda has a strong legacy of researching and treating GI disorders globally, and vedolizumab represents our focus on and commitment to patient communities.”

Takeda submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) in June, 2013, as well as a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) in March, 2013, seeking approval for vedolizumab for the treatment of adults with moderately to severely active CD and UC.

CD and UC are chronic diseases of the digestive tract. CD can involve all areas of the digestive tract, while UC typically affects the colon and rectum.CD and UC can be both painful and debilitating and patients may have bleeding, diarrhea, fatigue, weight loss and anemia, among other symptoms. Both diseases involve excess inflammation in the gut tissue that occurs when white blood cells infiltrate the gastrointestinal tract and may lead to serious complications.

Announced in early 2009, the GEMINI Studies is a phase 3 programme evaluating the effect of vedolizumab on clinical response and remission (along with effect on mucosal healing in UC), and long-term safety in moderately to severely active CD and UC patients who had failed at least one conventional therapy or a TNFa antagonist. The GEMINI programme consists of four separate studies – a placebo-controlled induction and maintenance study in patients with UC (GEMINI I), a placebo-controlled induction and maintenance study in patients with CD (GEMINI II), a placebo-controlled induction study in patients with CD (GEMINI III) and an open-label long-term safety study in patients with either CD or UC (GEMINI LTS).

Vedolizumab, under development for the treatment of CD and UC, is a humanized monoclonal antibody that specifically antagonizes the alpha4beta7 (a4ß7) integrin, inhibiting the binding of a4ß7 integrin to intestinal mucosal cell adhesion molecule (MAdCAM-1).  MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. The a4ß7 integrin is expressed on a subset of circulating white blood cells. These cells have been shown to play a role in mediating the inflammatory process in CD and UC.