Gut selective anti-inflammatory drugs! Takeda subcutaneous injection of entyvio in the treatment of active moderate to severe Crohn's disease (CD) phase III clinical success!

February 17, 2020 / BIOON / -- Takeda recently announced the results of the phase III visible 2 clinical trial to evaluate the treatment of Crohn's disease (CD) by subcutaneous injection (SC) of entyvio (vedolizumab) at the 2020 European Crohn and colitis Organization (Ecco) annual conference in Vienna, Austria This is a randomized, double-blind, placebo-controlled study conducted in adults with moderate to severe active CD to assess the efficacy and safety of entyvio SC in maintenance therapy 644 patients were enrolled in this study All patients did not respond to corticosteroids, immunomodulators or tumor necrosis factor - α (TNF - α) antagonists, or did not respond to them, or did not tolerate them In the study, all patients received two times of induction therapy with open label of entyvio 300mg intravenously (IV) at week 0 and week 2, and patients who reached clinical response at week 6 (n = 410) were randomly assigned to two groups and received subcutaneous injection of entyvio 108mg (SC) or placebo once every two weeks from week 6 to week 50 In this study, the clinical response was defined as a decrease in the Crohn's disease activity index (CDAI) score of ≥ 70 points from baseline (week 0) The primary end point was clinical remission, defined as a CDAI score of ≤ 150 at week 52 Secondary end points included: (1) enhanced clinical response, defined as a decrease of CDAI score by ≥ 100 points from baseline (week 0); (2) no corticosteroid remission, defined as patients taking oral corticosteroids at baseline, stopping oral corticosteroids and being in clinical remission at week 52 (CDAI score ≤ 150); (3) clinical remission at week 52 (CDAI score ≤ 150) The proportion of patients in the first treatment of anti TNF α The results showed that the study reached the primary end point: at week 52, a significantly higher proportion of patients in the entyvio SC treatment group achieved clinical remission compared to the placebo group (48.0% [n = 132 / 275] vs 34.4% [n = 46 / 134], P = 0.008) Secondary end point results showed that at week 52, the enhanced clinical response rate in the entyvio SC group was higher than that in the placebo group (52.0% [n = 143 / 275] vs 44.8% [n = 60 / 134]) Since the differences between the treatment groups were not statistically significant, the remaining secondary endpoints were not statistically tested Among the patients receiving corticosteroid treatment at baseline, the clinical remission rate without corticosteroid was 45.3% (n = 43 / 95) in the entyvio SC treatment group and 18.2% (n = 8 / 44) in the placebo group The study included patients who had not previously received anti TNF α therapy (primary treatment) and who had previously received anti TNF α therapy (treatment) The clinical remission rates of the entyvio SC group and the placebo group were 48.6% (n = 52 / 107) and 42.9% (n = 27 / 63) respectively at the 52nd week In this study, the safety results of entyvio SC were consistent with those of entyvio IV for CD patients Severe infection, second-line treatment and liver injury occurred in ≤ 5% of patients in the two treatment groups 2.5% of the patients in entyvio SC group detected anti vedolizumab antibody, and about half of them were neutralizing antibody Less than 3% of patients in the Entyvio SC treatment group reported injection site reactions According to s é verine vermeire, M.D., chairman of the Department of chronic diseases and metabolism of Ku Leuven and honorary member of Ecco, "the visible 2 study shows that after the first clinical response to induction therapy with intravenous injection of entyvio, entyvio SC can help patients with moderate to severe Crohn's disease to achieve clinical remission in the 52nd week These results suggest that enteric selective entyvio SC may provide a new treatment for patients who may prefer to self administer outside the hospital " Dr William sandborn, director of the center for inflammatory bowel disease at the University of California, said: "these data suggest that the safety of entyvio subcutaneous preparations appears to be similar to that of intravenous preparations If approved, the subcutaneous formulation, entyvio, along with the intravenous formulation, can provide patients with more treatment options to help meet their individual needs and preferences " Entyvio is a kind of intestinal selective biological preparation Its active ingredient is vedolizumab, which is a humanized monoclonal antibody It can specifically antagonize the α 4 β 7 integrin and inhibit the binding of α 4 β 7 integrin to the adhesion molecule MAdCAM-1 of intestinal mucosal cells 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 By inhibiting α 4 β 7 integrin, vedolizumab may limit the ability of some leukocytes to infiltrate intestinal tissue Entyvio intravenous preparation (IV) was approved by the United States and the European Union in May 2014 The product has been approved by more than 60 countries in the world for the treatment of adult patients with moderate to severe active ulcerative colitis (UC) and Crohn's disease (CD) Currently, Takeda is developing entyvio subcutaneous preparation (SC), which includes a pre filled syringe and a pre filled pen, and has been submitted to a number of major regulators around the world for regulatory review If approved, entyvio will be the only maintenance therapy for UC and CD that offers both intravenous (IV) and subcutaneous (SC) products It is worth mentioning that in December 2019, the US FDA issued a complete response letter (CRL) to entyvio SC's biological product licensing application (BLA), refusing to approve the preparation However, in CRL, FDA's questions have nothing to do with the data and conclusions supporting the key clinical trial visible-1 study 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 Original source: investigative subcutaneous formula of vedolizumab achievements clinical permission at week 52 in patients with moderate to severe active Crohn's disease