Entyvio (vedolizumab) is a maintenance treatment for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD), types of inflammatory bowel disease (IBD). Both the U.S. Food and Drug Administration (FDA) and the European Commission (EC) approved Entyvio for these patients.
How does Entyvio work?
In IBD, the immune response is excessive in the gastrointestinal (GI) tract. This results in the GI tract becoming inflamed, which can result in swelling, blockage, and infections.
An excess of white blood cells, gathering in the GI tract, can cause this inflammation. These white blood cells, also called leukocytes, enter the GI tract through an interaction between a protein on their surface and a protein on the walls of the blood vessels surrounding the GI tract. Like a key entering a lock, this highly specific interaction opens a “door” that allows white blood cells to enter the GI tract.
Entyvio works by blocking this interaction, meaning that white blood cell cannot access the GI tract, reducing the damage.
Entyvio in clinical trials
Takeda tested Entyvio in numerous clinical trials. The company sponsored four key Phase 3 trials worldwide to assess the safety and efficacy of Entyvio in patients with IBD: the GEMINI I (NCT00783718), GEMINI II (NCT00783692), GEMINI III (NCT01224171), and GEMINI-LTS (NCT00790933) trials. They measured patients’ clinical response to treatment — Entyvio given by intravenous (IV) infusion — using the Mayo score for ulcerative colitis and the Crohn’s disease activity index (CDAI) for Crohn’s.
GEMINI I assessed Entyvio’s efficacy in UC patients who had tried at least one conventional IBD therapy. By week 52 (one year), 42% of patients given Entyvio had maintained clinical disease remission. This percentage was 16% in the placebo group. Other measures such as mucosal healing were significantly higher in the Entyvio group (52%) than in those on a placebo (24%).
Both GEMINI II and III tested Entyvio in CD patients, over a 52-week (GEMINI II) and 10-week (GEMINI III) period. In GEMINI II, a significantly higher proportion of Crohn’s patients achieved clinical remission by week six in the Entyvio group compared to the placebo group (15% versus 7%). However, researchers saw no significant six-week difference in GEMINI III. At 52 weeks, a significant difference was seen, with 39% of Entyvio-treated patients in clinical remission compared to 22% of those in the placebo group.
GEMINI-LTS was a long-term open-label study to assess the safety, especially in terms of cancer risk, of Entyvio’s use over more than eight years in 1,785 people with UC and CD. Results, published in the journal Alimentary Pharmacology and Therapeutics, confirmed that the treatment appeared safe in the long term with the “number of malignancies … similar to that expected from an IBD population.”
Two other Phase 3 trials, VISIBLE 1 (NCT02611830) for ulcerative colitis and VISIBLE 2 (NCT02611817) for Crohn’s, evaluated the safety and efficacy of a subcutaneous (under-the-skin) formulation of Entyvio as a maintenance treatment in patients with moderate to severely active disease. Collectively, these studies enrolled more than 1,000 patients. The primary endpoint for both was clinical remission of symptoms. For UC, researchers defined remission as a drop in the Mayo score of more than three points and greater than 30% from baseline (starting measures), accompanied by a decrease in rectal bleeding. For CD, researchers defined remission as a CDAI score of less than 150.
Results showed remission rates of 46.2% for UC and 48% for CD after one year on subcutaneous Entyvio treatment. These remission rates were significantly higher than for participants who received a placebo, and were comparable to rates achieved with the IV formulation.
A ongoing and open-label extension study (NCT02620046) has enrolled UC and Crohn’s patients who completed the VISIBLE trials to continue testing the safety and effectiveness of subcutaneous Entyvio. It is expected to finish in February 2022.
Entyvio can cause side effects including upper respiratory infections, headache, and fatigue.
Last updated: May 15, 2020
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