Takeda's Vedolizumab Receives NMPA Approval in China for Two Indications: Ulcerative Colitis and Crohn’s Disease

By Holly

On March 12, the National Medical Products Administration (NMPA) updated Takeda’s novel anti-inflammatory drug “vedolizumab for injection” (Entyvio^®, vedolizumab) has changed to “Approval Completed – Pending Certificate Issuance.” As early as June 2019, when the New Drug Application (NDA) for vedolizumab was accepted by the Center for Drug Evaluation (CDE), Sina Medicine confirmed with the company that indications for both ulcerative colitis (UC) and Crohn’s disease (CD) were submitted simultaneously.

Ulcerative colitis (UC) and Crohn’s disease (CD) are the two most common forms of inflammatory bowel disease (IBD). Both are chronic, relapsing, and spontaneously remitting inflammatory progressive disorders of the gastrointestinal tract. Currently, the etiology of IBD remains unclear, and a cure is difficult to achieve. With onset frequently occurring during adolescence, IBD is a persistent chronic intestinal inflammatory disease that can lead to complications and even life-threatening conditions. Consequently, IBD imposes a substantial burden on patients, their families, and society.

Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin, inhibiting its interaction with mucosal addressin cell adhesion molecule-1 (MAdCAM-1). This mechanism prevents lymphocytes from entering the intestinal mucosa, thereby effectively reducing intestinal inflammatory responses. Lymphocytes expressing the α4β7 integrin on their surface are specifically homing to intestinal tissues; consequently, vedolizumab does not affect immune function or inflammatory responses in other tissues and organs.

Vedolizumab is the first and currently the only drug specifically targeting the gut-selective inflammatory signaling pathway. Its intravenous (IV) formulation was approved in the United States and the European Union in May 2014. To date, vedolizumab has been approved in more than 60 countries and regions worldwide for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) who have had an inadequate response, lost response, or were intolerant to conventional therapy or a TNFα antagonist.

Despite being on the market for over five years, Takeda continues to explore the efficacy and safety of vedolizumab in inflammatory bowel disease (IBD) and has conducted the first head-to-head biologic study in the field of ulcerative colitis (UC). In September 2019, Takeda announced further results from the Phase III VARSITY clinical trial (NCT02497469) evaluating vedolizumab for the treatment of UC.

VARSITY is a randomized, double-blind, double-dummy, multicenter, active-controlled, Phase IIIb study designed to evaluate the efficacy and safety of intravenous (IV) Entyvio versus subcutaneous (SC) Humira over one year (52 weeks) in patients with moderately to severely active ulcerative colitis (UC).

The results showed that the study met its primary endpoint, with Entyvio demonstrating superiority over Humira in terms of clinical remission rates at Week 52. Exploratory analyses indicated that, at Week 52, Entyvio achieved higher clinical remission rates compared to Humira in both the anti-TNFα-naïve subgroup and the anti-TNFα-experienced subgroup. Clinically, it is crucial to achieve remission across multiple disease domains when treating chronic, debilitating intestinal diseases such as ulcerative colitis (UC).

Furthermore, Takeda is also seeking breakthroughs in the formulation of Entyvio. Although the intravenous (IV) formulation can provide patients with faster relief, surveys have found that many patients prefer subcutaneous injection. To better meet patient needs, Takeda has been continuously evaluating the efficacy and safety of the subcutaneous (SC) formulation of vedolizumab.

VISIBLE-1 is a study validating the efficacy and safety of the subcutaneous (SC) formulation of vedolizumab, which included an intravenous (IV) vedolizumab control group. The results showed that at Week 52, a statistically significantly higher proportion of patients in the vedolizumab SC treatment group achieved clinical remission compared with the placebo group (46.2% vs. 14.3%, p < 0.001), thereby meeting the primary endpoint of the study.

Based on the aforementioned clinical trial data, Takeda is seeking approval for the subcutaneous (SC) formulation of vedolizumab. In April 2019, the European Medicines Agency accepted the marketing authorization application for the SC formulation of vedolizumab as a maintenance therapy for adult patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD). This application includes the pre-filled syringe and autoinjector pen formulations of vedolizumab SC.

March 12 marked a double celebration for Crohn’s disease (CD) patients in China. Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced today the launch of its ustekinumab injection (Stelara).^®, ustekinumab) in two formulations (intravenous [IV] and subcutaneous [SC]) have been approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response, lost response, or intolerance to conventional therapy or tumor necrosis factor-alpha (TNFα) antagonists.