Gut selective anti-inflammatory drugs! Takeda subcutaneous injection type entyvio treatment of inflammatory bowel disease in the United States has been refused approval by the FDA!

December 23, 2019 / BIOON / -- Takeda, a Japanese pharmaceutical giant, recently announced that the U.S Food and Drug Administration (FDA) has issued a complete response letter (CRL) to a biological product licensing application (BLA) of hypodermic injection type entryvio (vedolizumab) The BLA applied for approval of subcutaneous injection (SC) of entyvio as a maintenance therapy for adult patients with moderate to severe ulcerative colitis (UC) Currently, the application for marketing authorization (MAA) of entyvio SC preparation for the treatment of adult patients with moderate and severe UC and CD is also under review by the European Drug Administration (EMA) In the United States and the European Union, BLA and MAA applications include prefilled syringes and syringes for the SC preparation entyvio, and additional administration methods will provide more options for patients If approved, entyvio will be the only maintenance therapy available for both IV and SC products for UC and CD Entyvio is an intestinal selective biological agent Its IV preparation product was approved by FDA in 2014 to treat patients with moderate and severe UC and Crohn's disease (CD) In the United States, more than 150000 patients have been treated so far At present, entyvio IV has been marketed in more than 60 countries around the world Takeda said details in the CRL were being evaluated to gather the information needed to resolve the FDA's problems The company will work closely with the FDA It should be noted that in CRL, the questions raised by FD have nothing to do with the clinical data and conclusions supporting the key trials of BLA Takeda firmly believes that entyvio SC preparation will bring potential benefits to patients with moderate or severe UC The company is still committed to working with FDA to meet the needs of patients through this important route of administration, and to enhance patients' experience according to their treatment preferences and lifestyle The BLA and MAA submissions for the entyvio SC formulation were based on data from the critical phase III visible-1 study The study was a randomized, double dummy, double-blind, placebo-controlled study that included an IV entyvio control group A total of 383 patients with moderate to severe active UC were included in this study These patients did not respond to glucocorticoids, immunomodulators or tumor necrosis factor - α (TNF - α) antagonists or lost response or tolerance before the study In the study, patients received two doses of open label IV entyvio treatment in the first and second weeks, and patients with clinical remission were randomly assigned to three treatment groups in the sixth week: entyvio SC (108mg) + placebo IV treatment group (n = 106), entyvio IV (300mg) + placebo SC treatment group (n = 54), and placebo SC + placebo IV treatment group (n = 56) Subcutaneous injection is carried out every 2 weeks and intravenous infusion is carried out every 8 weeks The main purpose of the study was to evaluate the efficacy and safety of entyvio SC as a maintenance therapy Data showed that in the 52nd week of treatment, compared with the placebo group, there was a significantly higher proportion of patients in the entyvio SC treatment group achieved clinical remission (46.2% vs 14.3%, P < 0.001; clinical remission was defined as: Mayo score ≤ 2, and no single sub score > 1), reaching the main end point of the study Similar clinical remission rates were observed in the entyvio IV control group (42.6%) In addition, the entyvio SC treatment group also showed statistical advantages over the placebo group in terms of key secondary endpoints, including mucosal healing (56.6% vs 21.4%, P < 0.001) and persistent clinical remission (64.2% vs 28.6%, P < 0.001) The treatment group of entyvio SC was also higher than the placebo group in terms of the persistent clinical remission rate (15.1% vs 5.4%, P = 0.076) and the corticosteroid free clinical remission rate (28.9% vs 8.3%, P = 0.067), but there was no statistical significance Similar results were observed in the entyvio IV treatment group Further subgroup analysis showed that the clinical remission rate of entyvio SC was significantly higher than that of placebo (53.7% vs 18.9%, P < 0.001; 33.3% vs 5.3%, P = 0.023) In terms of safety, the incidence of adverse events (including serious adverse events and infection) was similar in the treatment group of entyvio SC and entyvio IV, with slight reaction at the injection site The incidence in the treatment group of entyvio SC was 9.4% (0% in the placebo group), and no patient stopped treatment The detection rate of anti entovio antibody (AVAs) was similar in entovio SC group and IV group (5.7% and 5.6%, respectively) Entyvio is an intestinal selective humanized monoclonal antibody, which was approved by the United States and the European Union in May 2014 At present, entyvio intravenous infusion has been approved by more than 60 countries in the world for the treatment of moderate to severe active ulcerative colitis (UC) or Crohn's disease (CD) in adult patients The active component of entyvio is vedolizumab, which is a humanized monoclonal antibody It can specifically antagonize the binding of α 4 β 7 integrin and inhibit the binding of α 4 β 7 integrin to MAdCAM-1 MAdCAM-1 was selectively expressed in gastrointestinal vessels and lymph nodes α 4 β 7 integrin is expressed in a group of circulating leukocytes, which have been proved to play an important role in mediating inflammation in CD and UC diseases It is worth mentioning that on March 9 this year, Takeda announced the results of varsity, the first phase IIIB study to evaluate entyvio (vedolizumab) in the treatment of moderate and severe UC, at the 14th European Organization for Crohn's disease and colitis (Ecco) conference held in Copenhagen, the capital of Denmark The results showed that, at the 52nd week of treatment, entyvio performed better in the primary end point of clinical remission compared with the flagship product of aimira (adalimumab, adalimumab) Original source: Takeda receives complete response letter from U.S FDA for the investigative subcutaneous formula of entryvio ® (vedolizumab) as a maintenance therapy in results with moderate to severe ultative colors