Entyvio (vedolizumab) is a human monoclonal antibody indicated for treating adult patients with moderate to severe ulcerative colitis (UC) and those with moderate to severe Crohn’s disease (CD).

Takeda Pharmaceuticals received approval for Entyvio from the US Food and Drug Administration (FDA) for the treatment of adult patients with moderate to severely active ulcerative colitis and Crohn’s disease in May 2014.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) also gave a positive opinion for Entyvio for the treatment of active UC and CD in March 2014. Takeda received marketing authorisation approval for Entyvio in Europe from the European Commission (EC) in May 2014.

Adult ulcerative colitis (UC) and Crohn’s disease (CD)

A subcutaneous injection for treatment of adult patients living with ulcerative colitis (UC).

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the inner lining of the large intestine, which includes the colon and rectum. The disease leads to abdominal discomfort, diarrhoea and gastrointestinal bleeding. It is estimated that 620,000 people in the US alone are affected by UC.

Crohn’s disease (CD) is a UC-related condition, which causes swelling and irritation to any part of the gastrointestinal tract and mainly affects the ileum. It has been diagnosed by an estimated half a million people in the US.

Entyvio’s mechanism of action

Entyvio contains humanised monoclonal antibody that works as antagonist to α4β7 integrin. The drug binds to α4β7 integrin, a mediator of gastrointestinal inflammation. Integrin receptors are proteins that function as mediators for cell-cell interactions.

The drug decreases inflammation in the gastrointestinal tract by blocking the entry of inflammation-stimulating lymphocytes. It is available in 300mg / IV dose, which can be injected intravenously.

Clinical trials on Entyvio

Takeda conducted two phase II clinical trials on Entyvio to evaluate the drug’s safety and efficacy in the treatment of ulcerative colitis. Studies enrolled around 900 patients who had not responded adequately to corticosteroids, immunomodulators, or tumour necrosis factor blocker medications. Subjects were observed through endoscopy for the purpose of evaluation.

Results demonstrated that patients treated with Entyvio achieved and maintained greater clinical response and a greater clinical remission, as well as achieved corticosteroid-free clinical remission when compared with placebo.

“Results demonstrated that patients treated with Entyvio achieved and maintained greater clinical response and a greater clinical remission.”

Takeda conducted three clinical trials to establish the efficacy and safety of Entyvio in treating Crohn’s disease. The studies enrolled more than 1,500 patients who had failed to respond adequately to corticosteroids, immunomodulators or TNF blocker medications.

Results demonstrated that patients treated with Entyvio achieved greater clinical response, clinical remission and corticosteroid-free clinical remission compared to placebo.

FDA and EU approvals were based on the results obtained from a Phase III clinical trial programme known as GEMINITM that involved four clinical studies conducted simultaneously by enrolling more than 2,700 UC and CD patients across 40 countries.

Three of the four studies were randomised, double-blind, placebo-controlled trials, GEMINI I (UC Trials I and II), GEMINI II (CD Trials I and III) and GEMINI III (CD Trial II). GEMINI I, II and III involved adult patients with moderate to severely active UC and CD, who had an inadequate response to immunomodulator therapy, loss of response, or intolerance to a TNF blocker and corticosteroids, or were corticosteroid dependant.

The results demonstrated that around 52% of patients treated with Entyvio reported adverse reactions compared with 45% of those treated with placebo. Serious adverse reactions were reported in 7% of patients treated with Entyvio compared with 4% of placebo-treated patients.

The drug’s side-effects as observed in the patients treated with Entyvio were headache, nasopharyngitis, arthralgia, nausea, pyrexia, fatigue, upper respiratory tract infection, cough, bronchitis, influenza, rash, back pain, pruritus, sinusitis, pain in extremities and oropharyngeal pain.

Marketing commentary

Entyvio is marketed by Takeda Pharmaceuticals in the US. Some other medications available for the treatment of UC include Sulfasalazine (Azulfidine) developed by Pfizer, Uceris (Budesonide) developed by Santarus and Cosmo Technologies and Remicade (Infliximab) discovered and developed by Janssen Biotech.

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