Takeda's Vedolizumab Nears Approval in China for Ulcerative Colitis and Crohn’s Disease

On March 4, the marketing application for Takeda Pharmaceutical’s novel anti-inflammatory drug “vedolizumab for injection” (acceptance numbers JXSS1900032 and 33) had its status updated to “under review” by the National Medical Products Administration (NMPA). The indicated indications reportedly include ulcerative colitis and Crohn’s disease.

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

Vedolizumab is the first and only drug specifically targeting the gut-selective inflammatory signaling pathway. Its intravenous formulation was approved in the United States and the European Union in May 2014. To date, the drug has been approved in more than 60 countries and regions worldwide for the treatment of 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 TNF-α antagonists.

Takeda Announces Results from VARSITY, the First Head-to-Head Phase IIIb Study Evaluating Vedolizumab for the Treatment of Moderate-to-Severe Ulcerative Colitis (UC)The results showed that at Week 52, a significantly higher proportion of patients in the vedolizumab group achieved clinical remission (31.3% [n=120/383] vs. 22.5% [n=87/386], p=0.0061) and mucosal healing (39.7% vs. 27.7%, p=0.0005) compared with the Humira group, thereby meeting the primary endpoint and one secondary endpoint. However, the difference in the other secondary endpoint, corticosteroid-free clinical remission, was not statistically significant. Regarding safety, the overall incidence of adverse events, infections, and serious adverse events was lower in the vedolizumab group than in the Humira group.

The aforementioned study is the first to directly compare two commonly used biologic therapies (selective α4β7 integrin inhibitor and anti-TNFα therapy) in patients with ulcerative colitis, and its findings can guide clinicians’ therapeutic decision-making regarding the use of biologics. Furthermore, to better meet patient needs, Takeda has been actively evaluating the efficacy and safety of the subcutaneous (SC) formulation of vedolizumab. A study designed to assess the efficacy and safety of vedolizumab SC has already yielded positive results, and in April 2019, the European Medicines Agency (EMA) accepted the marketing authorization application for vedolizumab SC as a maintenance therapy for adult patients with moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD).

Vedolizumab, owing to its excellent clinical performance, has seen its sales rise year by year since its market launch, exceeding 200 billion yen (approximately RMB 12 billion) in 2017. Furthermore, given its favorable efficacy and safety profile, vedolizumab was included in the first batch of the List of Overseas New Drugs in Urgent Clinical Need in November 2018.

In June 2019, the Center for Drug Evaluation (CDE) accepted the marketing application for vedolizumab. Given that the Phase III clinical trials of vedolizumab for ulcerative colitis and Crohn’s disease in China were both in the recruitment phase, the author speculates that this marketing application was submitted directly under the “Review and Approval Procedures for Overseas New Drugs in Urgent Clinical Need.” We sincerely hope that vedolizumab will be officially approved in China as soon as possible, thereby benefiting patients with ulcerative colitis and Crohn’s disease.

About Ulcerative Colitis and Crohn's Disease

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 conditions of the gastrointestinal tract; however, UC typically involves only the large intestine, whereas CD can affect any part of the gastrointestinal tract from the mouth to the anus. Furthermore, the clinical manifestations of UC and CD differ: UC typically presents with abdominal discomfort and altered bowel habits (such as bloody or purulent stools), while CD commonly presents with abdominal pain, diarrhea, and weight loss.

In recent years, with advancements in drug development, the therapeutic agents for ulcerative colitis (UC) and Crohn’s disease (CD) have gradually shifted from traditional immunomodulators (glucocorticoids, sulfasalazine, thiopurines) and nonsteroidal anti-inflammatory drugs (NSAIDs) to novel biologics and new pharmacological agents. Currently, the biologics and novel drugs used to treat these diseases primarily include anti-TNF agents, anti-integrin agents, anti-interleukin agents, and JAK inhibitors.

Original Title: Vedolizumab, a Head-to-Head Competitor to Humira, Is Set for Approval in China for the Treatment of Ulcerative Colitis and Crohn's Disease