Two studies published this week in the New England Journal of Medicine could bring relief to people suffering from Crohn’s disease and ulcerative colitis.
They report two international phase 3 clinical trials called GEMINI I and GEMINI II that found the investigational drug vedolizumab is an effective treatment for patients with the inflammatory bowel conditions for whom other treatments have not worked.
Lead investigator Dr Brian Feagan, a professor of medicine, and epidemiology and biostatistics at the Schulich School of Medicine & Dentistry at Western University in London, Canada, said:
“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 previous treatments have failed.”
Crohn’s disease (CD) and ulcerative colitis (UC), the two most common types of inflammatory bowel disease, are chronic and debilitating conditions that affect millions of people worldwide. Symptoms can range from diarrhea and bleeding, to fatigue, weight loss and anemia.
CD can affect all areas of the digestive tract, while UC typically affects the colon and rectum. Both diseases result from white blood cells infiltrating the digestive tract and causing excessive inflammation of gut tissue.
The conditions can become so severe that they lead to bowel obstruction or colon cancer, to the point where patients may need to have part of their bowel removed.
In 2012, a study of mice suggests a reason inflammatory bowel may lead to colon cancer could be due to a particular type of DNA damage that occurs during inflammation.
Prof. Feagan, who is also director of Robarts clinical trials at the Robarts Research Institute, says:
“The data from the GEMINI program suggest that vedolizumab may provide people living with CD and UC an additional option for inducing and maintaining clinical remission.”
The two trials are part of the four-study GEMINI program that is investigating vedolizumab in 2,700 patients in nearly 40 countries.
The program is the largest phase 3 trial to evaluate both CD and UC together and has been going for 15 years.
GEMINI I evaluated vedolizumab in patients with UC and GEMINI II evaluated the drug in patients with CD.
Both trials found patients fared better on vedolizumab than on placebo.
To join the trials, participants must have failed at least one conventional treatment, including glucocorticoids, immunomodulators and/or a tumor necrosis factor-alpha (TNF-a) antagonist.
The molecule investigated in the trials, vedolizumab, is a monoclonal antibody being developed by a subsidiary of the Japanese giant Takeda Pharmaceutical Company Limited who funded the trials.
The researchers are excited by the results because, as Prof. Feagan explains, “this molecule has the potential to be something quite different than our existing therapies.”
CD and UC are conditions in which the immune system is not responding properly, presumably to bacteria in the gut, Prof. Feagan says. And because the cause of the disregulation is unknown, patients have to take powerful anti-inflammatories to suppress their immune system.
However, these broad spectrum drugs affect inflammation not only in the gut, but also in the lungs, skin and brain, leading to side effects such as pneumonia, skin infections and blood infections.
Vedolizumab has the advantage that it focuses on the gut, leaving other parts of the body alone. The molecule specifically targets the transport of white blood cells in the gut.
Prof. Feagan:
“It has the potential advantage of selective suppression of the immune system and perhaps avoiding the side effects which are a major detriment to patient care.”
Ulcerative colitis
Study results for GEMINI I show that in patients with UC the drug met its primary endpoints of improved clinical response and reduction in rectal bleeding at 6 weeks and clinical remission at 52 weeks.
Also, a significantly greater percentage of patients with UC receiving the active drug achieved mucosal healing at 6 and 52 weeks, and glucocorticoid-free remission at 52 weeks, compared with placebo.
Crohn’s disease
Results for GEMINI II showed that in patients with CD, vedolizumab had a statistically significant improvement in the primary endpoint of clinical remission at 6 and 52 weeks compared with placebo.
There was no difference in clinical response between active drug and placebo at 6 weeks, but a greater proportion of CD patients showed response and glucocorticoid-free remission at 52 weeks.
Dr Asit Parikh, vice president for general medicine at Takeda, says:
“These clinical studies suggest that vedolizumab may have the potential to maintain clinical remission in the appropriate patients.”
Takeda has applied to the US Food and Drug Administration (FDA) for vedolizumab to be licensed for the treatment of adults with moderately to severely active CD and UC. The company has also applied to the European Medicines Agency.
Written by Catharine Paddock PhD