Entyvio by Takeda Pharmaceuticals

BACKGROUND^1,2

Entyvio (vedolizumab), manufactured by Takeda Pharmaceuticals, was approved in May 2014 for the treatment of adult patients with moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD) refractory to therapy with tumor necrosis factor (TNF)-blocking agents, immunomodulators, or corticosteroids. With a novel mechanism of action, this biologic agent provides a viable secondline option in the treatment of these gastrointestinal (GI) disorders.

PHARMACOLOGY/PHARMACOKINETICS^1,2

The interaction of the alpha 4 beta 7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) contributes to the chronic inflammation implicated in UC and CD. Entyvio is a humanized monoclonal antibody and, as an integrin receptor antagonist, it specifically binds to the alpha 4 beta 7 integrin on certain memory T cells to block its interaction with MAdCAM-1, which is expressed on gut endothelial cells. This prevents these T cells from migrating across the endothelium into inflamed GI tissue. With the recommended dosing regimen, Entyvio exhibits a volume of distribution of 5 L, a linear clearance of 0.157 L/day, and a half-life of 25 days.

DOSING^1,2

The recommended dose of Entyvio is 300 mg administered as a 30-minute intravenous (IV) infusion at 0, 2, and 6 weeks, and then every 8 weeks thereafter. If the patient does not show clinical improvement by week 14, therapy should be discontinued. Prior to administration, Entyvio must be reconstituted with 4.8 mL of sterile water for injection and diluted in 250 mL of normal saline; after the infusion, the line should be flushed with 30 mL of normal saline. Due to the risk of anaphylaxis or other hypersensitivity reactions that may occur, patients should be observed throughout the infusion with appropriate monitoring and support measures readily available.

CLINICAL EFFICACY^3,4

The approval of Entyvio was obtained based on results of the GEMINI 1 study for UC and GEMINI 2 study for CD, both of which included patients who had not adequately responded to treatment with corticosteroids, immunomodulators, or TNF-blocking medications.

The GEMINI 1 study group conducted 2 integrated, double-blind, randomized, placebo-controlled trials for both induction and maintenance treatment of moderate to severe UC. For induction therapy, 374 patients (cohort 1) were randomized in a 3:2 ratio to IV treatment with Entyvio 300 mg or placebo at weeks 0 and 2 and 521 patients (cohort 2) received open-label Entyvio, also at weeks 0 and 2.

Patients receiving Entyvio from either cohort who had a clinical response at week 6 were randomized in a 1:1:1 ratio to be maintained on Entyvio every 4 or 8 weeks or switched to placebo for up to 52 weeks. At week 52, 44.8% of patients receiving Entyvio every 4 weeks, 41.8% of patients receiving Entyvio every 8 weeks, and 15.9% of patients receiving placebo went into clinical remission (P <.001 for each Entyvio group compared with placebo).

With a similar study design, the GEMINI 2 study group conducted 2 integrated, double-blind, randomized placebo-controlled trials for both induction and maintenance treatment of moderate to severe CD. For induction therapy, 368 patients (cohort 1) were randomized 3:2 to IV treatment with Entyvio 300 mg or placebo at weeks 0 and 2 and 747 patients (cohort 2) received open-label Entyvio, also at weeks 0 and 2.

Disease status, measured by CD Activity Index (CDAI), was assessed at week 6. Patients receiving Entyvio from either cohort who had a clinical response, deemed as a >70-point decrease in CDAI score, at week 6 were randomized in a 1:1:1 ratio to be maintained on Entyvio every 4 or 8 weeks or switched to placebo for up to 52 weeks. Among those patients who had a clinical response in the induction phase, 39.0% of those assigned to Entyvio every 8 weeks and 36.4% of those assigned to Entyvio every 4 weeks (P <.001 and P = .004, respectively) were in clinical remission at Week 52, compared with 21.6% of those assigned to placebo.

MEDICATION SAFETY^1,2,5

The most common (>10% incidence) adverse effects observed in both GEMINI trials were headache, arthralgia, and nasopharyngitis. Rare, serious adverse events have occurred with use of Entyvio, including hypersensitivity and infusion-related reactions, severe infections, and hepatic injury.

AVAILABILITY AND COST^1,6

Entyvio is supplied as a 300-mg lyophilized cake in a sterile 20-mL single-dose vial. Entyvio has an acquisition cost of $5782 per vial.

Ashley L. Pappas, PharmD, BCPS, is a drug information specialist at University of North Carolina (UNC) Hospitals and an adjunct assistant professor at the UNC Eshelman School of Pharmacy.Sandra Hanna, PharmD candidate, is a fourth-year pharmacy student at the UNC Eshelman School of Pharmacy and an intern at the UNC Hospital Drug Information Center in Chapel Hill, North Carolina.

References

• Entyvio [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2014.
• Vedolizumab. DrugPoints Summary. Micromedex 2.0. Greenwood Village, CO: Truven Health Analytics, Inc. www.micromedexsolutions.com. Accessed April 21, 2015.
• Feagan BG, Rutgeerts P, Sands BE, et al; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710. doi: 10.1056/NEJMoa1215734.
• Sandborn WJ, Feagan BG, Rutgeerts P, et al; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8):711-721. doi: 10.1056/NEJMoa1215739.
• Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151(1):97-110.
• Pricing obtained from AmerisourceBergen.