Date: 2017-08-22
Type of information: Submission of an NDA
Product name: Entyvio®
Compound: vedolizumab
Therapeutic area: Autoimmune diseases - Inflammatory diseases - Digestive diseases
Action mechanism:
- monoclonal antibody. Vedolizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody directed against the human lymphocyte integrin alpha4beta7. The alpha4beta7 integrin is expressed on the surface of a discrete subset of memory T lymphocytes that preferentially migrate into the gastrointestinal tract and cause the inflammation that is characteristic of ulcerative colitis and Crohn’s disease. By binding to the alpha4beta7 integrin, vedolizumab selectively inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing their transmigration into inflamed parenchymal tissue.
Company: Takeda Pharmaceutical (Japan)
Disease:
- treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFalpha) antagonist
- Crohn's disease
Latest news:
- • On August 22, 2017, Takeda Pharmaceutical announced today that it has submitted a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare in Japan for the vedolizumab for the treatment of adults with moderately to severely active ulcerative colitis. The NDA filing included data from Study CCT-101, a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study investigating the efficacy, safety and pharmacokinetics of vedolizumab induction and maintenance treatment involving 292 Japanese patients with moderate or severe ulcerative colitis. The NDA filing also included data from the international, randomized, double blind, placebo-controlled GEMINI I pivotal Phase 3 study of vedolizumab induction and maintenance treatment involving 895 patients with moderate to severe UC.
- Vedolizumab is already approved in the European Union and the U.S. in May 2014 for this indication (See below)
- • On May 27, 2014, Takeda Pharmaceutical announced that the European Commission has granted Marketing Authorisation for Entyvio® (vedolizumab), first and only biologic therapy to be approved simultaneously for the treatment of adults with moderately to severely active ulcerative colitis and adults with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNF?) antagonist. The Marketing Authorisation Application submission is supported by the GEMINI™ Studies, a clinical program investigating vedolizumab in 2,700 patients across nearly 40 countries. It is the largest Phase 3 clinical trial program conducted to date evaluating both UC and CD patient populations in parallel. Enrolled patients had failed at least one conventional therapy, including corticosteroids, immunomodulators and/or a tumor necrosis factor-alpha (TNF?) antagonist. TNF? antagonist and conventional therapy failure patients included those with inadequate response (primary non-responders), loss of response (secondary non-responders) or those who were intolerant.
- • On May 20, 2014, the FDA approved Entyvio® (vedolizumab) injection to treat adult patients with moderate to severe ulcerative colitis and adult patients with moderate to severe Crohn‘s disease. Entyvio® is approved to treat those conditions when one or more standard therapies (corticosteroids, immunomodulators, or tumor necrosis factor blocker medications) have not resulted in an adequate response. The safety and effectiveness of Entyvio® for ulcerative colitis were established in two clinical trials involving approximately 900 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Evaluations of patients included measures of stool frequency, rectal bleeding, endoscopic findings and a physician‘s overall assessment. Results showed that a greater percentage of participants treated with Entyvio® compared to a placebo achieved and maintained clinical response, achieved and maintained clinical remission, achieved corticosteroid-free clinical remission, and as seen during endoscopy, had improved appearance of the colon.
- The safety and effectiveness of Entyvio® for Crohn‘s disease were established in three clinical trials involving approximately 1,500 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved clinical response, achieved clinical remission, and achieved corticosteroid-free clinical remission. The most serious risks associated with Entyvio® include serious infections, hypersensitivity and infusion-related reactions; and hepatotoxicity. Another type of integrin receptor antagonist has been associated with progressive multifocal leukoencephalopathy, a rare and often fatal opportunistic infection of the central nervous system. PML is caused by a virus and typically only occurs in patients whose immune systems are compromised. There were no cases of PML identified among Entyvio clinical trial participants.
- In Entyvio® clinical trials, participants were actively monitored for PML with frequent and regular screenings, and evaluations of any new, unexplained neurological symptoms, as necessary. Because clinical trials are conducted under tightly controlled conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates that might be observed in practice. Therefore, while there were no cases of PML seen among patients participating in Entyvio clinical trials, there remains uncertainty regarding the risk of PML in patients taking Entyvio®. Health care professionals should monitor patients on Entyvio® for any new onset, or worsening, of neurological signs and symptoms. The FDA will continue to work with the sponsor to further investigate the risk of PML through a required post-marketing study and enhanced, expedited adverse event reporting.
- • On March 20, 2014, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a marketing authorisation for Entyvio®, 300 mg powder for concentrate for solution for infusion intended for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNF alpha) antagonist and adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNF alpha) antagonist. The benefits of Entyvio® in ulcerative colitis are its ability to induce clinical response, remission and mucosal healing in patients with no prior TNF alpha antagonist exposure as well as in those who have failed prior TNF alpha antagonist therapy. The most common side effects are nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache, cough and Infusion-related reactions. A pharmacovigilance plan for Entyvio®will be implemented as part of the marketing authorisation.
- • On March 7, 2013, Takeda Pharmaceutical has announced that a Marketing Authorisation Application (MAA) has been submitted to the European Medicines Agency (EMA) for vedolizumab, an investigational, gut-selective humanized monoclonal antibody for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease, the two most common types of inflammatory bowel disease (IBD). The MAA submission was supported by Phase 3 clinical studies, GEMINI I, GEMINI II, GEMINI III and GEMINI LTS (Long-term Safety), which are part of the GEMINI Studies™, a four-study clinical research program to investigate the efficacy and safety of vedolizumab on clinical response and remission in moderately to severely active Crohn’s disease and ulcerative colitis patients, who had failed at least one conventional or anti-TNFalpha therapy.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE: 2013-03-07
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-05-20
UE authorization: 2014-05-27
Favourable opinion UE: 2014-03-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
