306Takeda FlypaperVedolizumab, a new drug, initially developed by Millennium Pharmaceuticals that was taken over by Takeda Pharmaceuticals, is a monoclonal antibody, and has been under trial for use in ulcerative colitis (UC) and Crohn’s disease (CD), that are part of Inflammatory Bowel Disease (IBD) This antibody has been found to be more effective than a placebo in treating ulcerative colitis as it has shown to offer significant relief and even remission. For CD the results are not as effective as the clinical response percentage was much lower.

The latest research study shows positive results

The Phase 3, GEMINI I studied patients with UC and the GEMINI II one studied patients with Crohn’s. The GEMINI I study was conducted by Brian G. Feagan, MD, from the University of Western Ontario in London, Canada, and colleagues. They investigated nearly 900 patients with active UC who were divided into two groups one of which received Vedolizumab, while the other received a placebo. The drugs were given intravenously at an interval of two weeks.

After six weeks the 47 percent of the patients who received Vedolizumab had met significant end points of the trial. These patients were then randomly assigned to receive further Vedolizumab or a placebo every four or every eight weeks for a year. After a year 42-45 percent of the patients on the drug were in remission whereas only 16 percent of the placebo group experienced remission.

The GEMINI II trial was conducted by William J. Sandborn, MD, from the University of California in San Diego and colleagues and featured 1,100 patients with Crohn’s disease. This group was also divided and some were given Vedolizumab while others received a placebo. After six weeks, 31 percent had given a positive response to the drug. After a year’s further treatment, 36-39 percent of the patients were in remission when compared to 22 percent of the placebo group that were also in remission.

How the drug works

Vedolizumab works by antagonizing the alpha4beta7 (α4β7) integrin, which is part of the leukocytes or white blood cells in the body responsible for the inflammation that gives rise to inflammatory bowel disease (IBD). ‘This is a completely new mechanism in the ulcerative colitis space and offers the promise of improvement over the existing leukocyte trafficking inhibitor because it does not involve the brain,’ observed David T. Rubin, MD, co-director of the Inflammatory Bowel Disease Center at the University of Chicago. Other drugs that are taken for the treatment of IBD may result in some cases of progressive multifocal leukoencephalopathy (PML). In the study, none of the patients developed this disorder.

What this means that Vedolizumab, thanks to its greater efficacy and fewer associated side effects, may be the first line of treatment for ulcerative colitis after steroids. For Crohn’s it may be used only after drugs like anti-TNFs have been tried.

Other treatment for IBD

According to CDC, 1.4 million people in the U.S.A. alone suffer from some form or the other of Inflammatory Bowel Disease (IBD). However, these are conservative estimates as there is no gold standard to diagnose this disease. And this figure does not take into account global statistics on the disease. CD and UC are two forms of IBD, with Crohn’s being significantly worse since it affects both the small and large intestine, occurring anywhere. It also causes blockages, ulcers and increases colon cancer risk. UC occurs in the large intestine and affects the top layers of the colon unlike CD. It is also more evenly distributed though patients are also at risk of developing colon cancer.

The four major classes of medication used today to treat ulcerative colitis are aminosalicylates (5-ASA), steroids, immune modifiers (azathioprine, 6-MP, and methotrexate), and antibiotics (metronidazole, ampicillin, ciprofloxacin, others). The first line of treatment is usually an aminosalicyclate and then, depending on patient response the severity of the disease, further drugs are given. Antibiotics can often cause colitis so are used with caution in patients of IBD. Steroids are usually given during a severe flare-up. Again steroid drugs also cause acidity and other digestive problems.

Other drugs given to patients of IBD include tumor necrosis factor inhibitors, monoclonal antibodies, H2-receptor antagonists (like ranitidine or cimetidine), proton pump inhibitors, anti diarrheal agents and more. Both Crohn’s and UC are diseases that do not simply go away – they have to be managed and there are times when patients are in remission and times when they have flare-ups. In severe cases of UC, the colon is surgically removed (colectomy).
Takeda has already filed for market authorization application with the F.D.A. in June this year and in the European Union in March. This study has boosted the company’s likelihood of getting the approval. If approved, it may hit the market some time in 2104.

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