Takeda's Vedolizumab Submits NDA in China, Showing Superiority Over Humira in Head-to-Head UC Trial

Today (June 20), the official website of the Center for Drug Evaluation of the National Medical Products Administration showed that Takeda Pharmaceutical's new anti-inflammatory drug "Vedolizumab for Injection" (Entyvio®, vedolizumab) has had its marketing application accepted in China, with the acceptance number JXSS1900032.

Robust Efficacy: Head-to-Head Phase IIIb Results in UC Superior to Humira

Vedolizumab is a humanized monoclonal antibody that specifically antagonizes the α4β7 integrin, inhibiting its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) but not to vascular cell adhesion molecule-1 (VCAM-1). At the 14th Congress of the European Crohn’s and Colitis Organisation (ECCO) held in March 2019, Takeda announced the results of VARSITY, the first head-to-head Phase IIIb study evaluating vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC). The study aimed to assess the efficacy and safety of intravenous vedolizumab compared with subcutaneous Humira.

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 (favoring Humira).

In terms of safety, vedolizumab also demonstrated a better profile; during the 52-week treatment period, the overall incidence of adverse events in the vedolizumab group,Incidence of infection,Incidence rates of serious adverse events were alllower, at 62.7% vs. 69.2%, 33.5% vs. 43.5%, and 11.0% vs. 13.7%, respectively.

This is the first study to directly compare two commonly used biologic therapies (selective anti-α4β7 integrin therapy and anti-TNFα therapy) in patients with ulcerative colitis (UC). These positive results are exciting for Takeda and can guide physicians’ treatment decisions regarding the use of biologic therapies.

Breakthrough in Dosage Forms: Providing More Options for Patients

The intravenous (IV) formulation of vedolizumab was first approved for marketing in the United States and the European Union in May 2014. It has since received approval 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 intolerance to conventional therapies or TNF-α antagonists.

Although the intravenous (IV) formulation can provide patients with rapid relief, surveys have found that many patients prefer the subcutaneous injection route. To better meet patient needs, Takeda has been actively validating the efficacy and safety of the subcutaneous (SC) formulation of vedolizumab.

VISIBLE-1 is a study conducted to validate 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. A similar clinical remission rate was observed in the vedolizumab IV treatment group (42.6%). Furthermore, the vedolizumab SC treatment group demonstrated statistical superiority over the placebo group in key secondary endpoints, including mucosal healing (56.6% vs. 21.4%, p<0.001) and durable clinical remission (64.2% vs. 28.6%, p<0.001). Although the rates of durable clinical remission (15.1% vs. 5.4%, p=0.076) and corticosteroid-free clinical remission (28.9% vs. 8.3%, p=0.067) were higher in the vedolizumab SC group than in the placebo group, these differences were not statistically significant. Similar results were observed in the vedolizumab IV treatment group. Regarding safety, the incidence of adverse events was similar between the vedolizumab SC and vedolizumab IV treatment groups.

Based on the aforementioned research data, Takeda is also actively seeking approval for the subcutaneous (SC) formulation of vedolizumab. In early April 2019, Takeda announced that the European Medicines Agency (EMA) had accepted its 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). The application includes both pre-filled syringes and injection pens for the SC formulation of vedolizumab. If approved, vedolizumab will become the only maintenance therapy offering both intravenous (IV) and SC products for UC and CD.

We look forward to the expedited approval of the new vedolizumab formulation, providing more treatment options for patients with ulcerative colitis (UC) and Crohn’s disease (CD).