Gut reaction

OSAKA, Japan—Within a week in May, regulatory authorities in the United States and Europe gave Takeda’s Entyvio (vedolizumab) the green light for the two most common inflammatory bowel diseases, ulcerative colitis (UC) and Crohn’s disease (CD). In addition to the United States, the drug is now authorized for marketing in 28 European Union (EU) member states, along with Iceland, Norway and Liechtenstein.

Thus, Entyvio has become the first and only biologic therapy to be approved simultaneously for these two conditions, in patients who have had an inadequate response with, lost response to or were intolerant to either conventional therapy or a tumor necrosis factor-alpha antagonist. Standard therapies for UC and CD include corticosteroids, immunomodulators and tumor necrosis factor blocker medications.

Entyvio is a novel alpha-4 beta-7 integrin antagonist that blocks a key inflammatory marker on white blood cells. Takeda acquired the humanized monoclonal antibody drug with its $8.8-billion purchase of Millennium Pharmaceuticals in 2008. Because the two conditions affect more than four million people worldwide, many analysts believe the drug could attain blockbuster status, achieving sales of more than $1 billion by 2020.

U.S. Food and Drug Administration and EU approvals were based on the results obtained from a Phase 3 clinical trial program known as GEMINI. It involved four clinical studies that were conducted simultaneously by enrolling more than 2,700 UC and CD patients across 40 countries, making it the largest Phase 3 clinical trial program conducted to date evaluating both UC and CD patient populations in parallel. Patients in the study had failed at least one conventional therapy.

“Patients with moderately to severely active ulcerative colitis or Crohn’s disease, and the healthcare professionals who care for them, need additional new treatment options,” said Douglas Cole, president of Takeda Pharmaceuticals U.S.A. Inc.

“In clinical trials, vedolizumab demonstrated statistically significant efficacy on a range of endpoints and was well-tolerated in trials for both UC and CD,” added Trevor Smith, Takeda’s head of commercial operations in Europe and Canada.

The Entyvio dose regimen is 300 mg infused intravenously over approximately 30 minutes at zero, two and six weeks, then every eight weeks thereafter. Patients should be observed during infusion and until the infusion is complete, according to the approving agencies. The most common adverse reactions reported with Entyvio were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain and pain in extremities.

UC is a chronic disease that causes inflammation and ulcers in the inner lining of the large intestine, including the colon and the rectum. The inflammation can lead to abdominal discomfort, gastrointestinal bleeding or pus and diarrhea. Crohn’s disease is a chronic inflammatory condition that causes inflammation, or swelling, and irritation of any part of the gastrointestinal tract. Common symptoms may include abdominal pain, diarrhea, rectal bleeding, weight loss and fever.

There is no known cause for UC or CD, although many researchers believe that the interaction between genes, the body’s immune system and environmental factors may play a role. While there is also no cure for these diseases, new therapies can help patients failing to respond to standard treatment to manage the conditions and reduce symptoms.

As Dr. Paul Rutgeerts, emeritus professor of medicine at Catholic University of Leuven, Belgium, explained, “Ulcerative colitis and Crohn’s disease are serious conditions which can have a devastating impact on patients, many of whom are in early adulthood when they receive a diagnosis. As physicians, our aim is to help patients achieve and maintain remission and disease control. It provides us with a new therapeutic option to help us to tackle these challenging diseases.”

“Entyvio is a new option that works to block important contributors to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease,” said Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at the Northwestern University Feinberg School of Medicine. “The clinical trial program evaluated the efficacy and safety profile of Entyvio and demonstrated that Entyvio has the potential to help adult patients with moderately to severely active UC or CD successfully manage their disease.”