New Phase 3 Data Show Investigational Subcutaneous Formulation of Vedolizumab Meets Primary Endpoint in Achieving Clinical Remission at Week 52 in Patients with Moderately to Severely Active Ulcerative Colitis
Takeda Pharmaceutical Company Limited [TSE:4502] (“Takeda”) today announced top-line results from the VISIBLE 1 clinical trial evaluating the efficacy and safety of an investigational subcutaneous (SC) formulation of vedolizumab for maintenance therapy in adult patients with moderately to severely active ulcerative colitis (UC) who achieved clinical response* at week 6 following two doses of open-label vedolizumab intravenous (IV) induction therapy. In the primary endpoint of the trial, a statistically significant proportion of patients receiving vedolizumab SC beginning at week 6 and every two weeks following achieved clinical remission** at week 52 compared to placebo. The safety data were consistent with the known safety profile of vedolizumab, and no new safety signals were identified. Further data from the trial will be presented at a future scientific congress.
“Meeting the primary endpoint of the VISIBLE 1 trial marks an exciting milestone in our approach to developing new ways to meet the needs of the ulcerative colitis patient community,” said Asit Parikh, MD PhD, Head of Takeda’s Gastroenterology Therapeutic Area Unit. “These results are encouraging and build on vedolizumab’s robust clinical profile with more than 200,000 patient years of exposure. We plan to discuss these data with health authorities with the aim of bringing this innovative treatment option to patients.”
VISIBLE 1 is a pivotal phase 3, randomized, double-dummy, double-blind, placebo-controlled study, with a vedolizumab IV reference arm, to evaluate the safety and efficacy of an investigational SC formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active UC who have achieved clinical response at week 6 following two doses of open-label vedolizumab IV therapy at weeks 0 and 2. The study enrolled 384 patients, all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or tumor necrosis factor-alpha (TNFα)-antagonist therapy prior to being enrolled. Patients who achieved clinical response at week 6 were randomized into one of three treatment groups, vedolizumab SC 108 mg and placebo IV, vedolizumab IV 300 mg and placebo SC, or placebo SC and placebo IV. Subcutaneous doses were administered every two weeks and intravenous doses were administered every eight weeks.
Additional endpoints assessed in VISIBLE 1 include the proportion of subjects achieving mucosal healing at week 52,*** durable clinical response,ǂ durable clinical remissionǂǂ and corticosteroid-free clinical remission at week 52.ǂǂǂ
|* Clinical response is defined as a reduction in Mayo score of ≥3 points and ≥30% from baseline (week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.|
|** Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.|
|*** Mucosal healing is defined as a Mayo endoscopic subscore of ≤1 point.|
|ǂ Durable clinical response is defined as clinical response at weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from baseline (week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.|
|ǂǂ Durable clinical remission is defined as clinical remission at weeks 6 and 52.|
|ǂǂǂ Corticosteroid-free clinical remission is defined as participants using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52. Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.|
About the VISIBLE clinical trial program
The VISIBLE clinical trial program aims to assess the efficacy and safety of an investigational subcutaneous (SC) formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD).
VISIBLE consists of three phase 3 studies involving over 1,000 patients which includes two randomized, double-blind, placebo-controlled studies examining the percentage of participants achieving clinical remission at week 52 in UC and CD respectively, and an open-label extension study to determine the long-term safety and efficacy of vedolizumab SC consisting of patients who have completed one of the randomized clinical trials.
About Ulcerative Colitis and Crohn’s Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are two of the most common forms of inflammatory bowel disease (IBD). Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal (GI) tract that are often progressive in nature. UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus. CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine. UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus. CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss. The cause of UC or CD is not fully understood; however, recent research suggests hereditary, genetics, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC or CD.
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation. It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. The alpha4beta7 integrin is expressed on a subset of circulating white blood cells. These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD). By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.
Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist. Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with over 200,000 patient years of exposure to date.
Vedolizumab is indicated 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 tumor necrosis factor-alpha (TNFα) antagonist.
Vedolizumab is indicated for the treatment of 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 tumor necrosis factor-alpha (TNFα) antagonist.
Important Safety Information
Hypersensitivity to the active substance or to any of the excipients.
Special warnings and special precautions for use
Vedolizumab should be administered by a healthcare professional equipped to manage hypersensitivity reactions, including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab. Observe all patients during infusion and until the infusion is complete.
In clinical studies, infusion-related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity. If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines). If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated (e.g., epinephrine and antihistamines). Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their risks.
Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity. Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Vedolizumab treatment is not to be initiated in patients with active, severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with vedolizumab. Caution should be exercised when considering the use of vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment. Before starting treatment with vedolizumab, screening for tuberculosis may be considered according to local practice. Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect on the gut. Although no systemic immunosuppressive effect was noted in healthy subjects, the effects on systemic immune system function in patients with inflammatory bowel disease are not known. No cases of PML were reported in clinical studies of vedolizumab however, healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of neurological signs and symptoms, and consider neurological referral if they occur. If PML is suspected, treatment with vedolizumab must be withheld; if confirmed, treatment must be permanently discontinued. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months.
The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. Immunomodulatory medicinal products may increase the risk of malignancy.
Prior and concurrent use of biological products
No vedolizumab clinical trial data are available for patients previously treated with natalizumab. Caution should be exercised when considering the use of vedolizumab in these patients. No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of vedolizumab in such patients is not recommended.
Prior to initiating treatment with vedolizumab all patients should be brought up to date with all recommended immunizations. Patients receiving vedolizumab may receive non-live vaccines (e.g., subunit or inactivated vaccines) and may receive live vaccines only if the benefits outweigh the risks.
Adverse reactions include: nasopharyngitis, headache, arthralgia, upper respiratory tract infection, bronchitis, influenza, sinusitis, cough, oropharyngeal pain, nausea, rash, pruritus, back pain, pain in extremities, pyrexia, and fatigue.
Please consult with your local regulatory agency for approved labeling in your country.
For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO ® .
Takeda’s Commitment to Gastroenterology
Gastrointestinal (GI) diseases can be complex, debilitating and life-changing. Recognizing this unmet need, Takeda and our collaboration partners have focused on improving the lives of patients through the delivery of innovative medicines and dedicated patient disease support programs for over 25 years. Takeda aspires to advance how patients manage their disease. Additionally, Takeda is leading in areas of gastroenterology associated with high unmet need, such as inflammatory bowel disease, acid-related diseases and motility disorders. Our GI Research & Development team is also exploring solutions in celiac disease and liver diseases, as well as scientific advancements through microbiome therapies.
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Around 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries.
For more information, visit https://www.takeda.com/newsroom/.
Takeda Pharmaceutical Company Limited
For media outside Japan:
For Japanese media:
Om Business Wire
(c) 2018 Business Wire, Inc., All rights reserved.
Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.
Følg saker fra Business Wire
Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.
Siste saker fra Business Wire
Gilead and Carna Biosciences Announce Research and Development Collaboration to Develop Novel Immuno-Oncology Therapies24.6.2019 23:00:00 CEST | Pressemelding
Gilead Sciences, Inc. (NASDAQ: GILD) and Carna Biosciences Inc. (JASDAQ: 4572) today announced that the companies have entered into a research and development collaboration to develop and commercialize small molecule compounds in immuno-oncology and to access Carna’s proprietary lipid kinase drug discovery platform. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190624005487/en/ Under the terms of the license agreement, Gilead will license from Carna worldwide rights to develop and commercialize inhibitors against an undisclosed immuno-oncology target. In connection with this agreement, Carna will receive an upfront payment of $20 million and is eligible to receive up to an additional $450 million in potential milestone payments upon achievement of certain development and commercial milestones. Carna will also receive royalties on future net sales. "We are delighted to partner with Gilead on our immuno-oncology pipeline targ
iMarketKorea Switches to Rimini Street Support for its SAP Application24.6.2019 22:00:00 CEST | Pressemelding
Rimini Street, Inc. (Nasdaq: RMNI), a global provider of enterprise software products and services, the leading third-party support provider for Oracle and SAP software products and a Salesforce partner, today announced that iMarketKorea, the country’s leading B2B e-commerce company, has switched from SAP to Rimini Street support for their SAP ECC system. By switching to Rimini Street, iMarketKorea was able to reduce its annual support fees by 50 percent and are now able to run their current stable ERP system for a minimum of 15 years from the time they moved to Rimini Street, without being forced to upgrade by SAP’s published 2025 end of mainstream maintenance window for ECC 6. Because of the premium level of ERP support the company now receives, iMarketKorea’s IT staff have been relieved of the day to day back office system maintenance, which is now entirely handled by Rimini Street, and are able to focus on and support more strategic projects within their company. This press release
IFF and ISIPCA Celebrate First Master of Scent Design Graduating Class24.6.2019 20:15:00 CEST | Pressemelding
Regulatory News: IFF (NYSE:IFF) (Euronext Paris:IFF) (TASE:IFF), a leading innovator of taste, scent, and nutrition & ingredients, and ISIPCA, a prestigious higher education institution in the field of perfume, cosmetics, and flavoring, today celebrate the first Master of Scent Design and Creation graduating class of their collaborative program, established in 2016. “This is an historic day with many reasons to celebrate,” said Nicolas Mirzayantz, Scent Division CEO, IFF. “This is the first Masters of Scent Design & Creation graduating class from the first collaboration of its kind in the industry. We are thrilled at the sheer quality and passion of the well-trained and talented class, who are poised and ready to contribute to the world of fragrance. And we are happy to see such a diverse and inclusive group, reflecting the consumers for whom they will create.” The three-year program, based in Versailles, France, offers students a strong foundation in the art of perfumery, including an
3,900-Acre Wyoming “Holy Cow Ranch” Neighboring Bighorn National Forest to Auction via Concierge Auctions24.6.2019 19:58:00 CEST | Pressemelding
A 3,900-acre property located halfway between Yellowstone Park and Mount Rushmore in Sheridan, Wyoming – affectionately known as Holy Cow Ranch – will auction next month via leading global firm Concierge Auctions. The property features five structures including a guest lodge and owner’s residence, a pool with pool house, tennis courts, and miles of Bighorn National Forest frontage. Previously listed for $23.5 million, 43 Rapid Creek Road will auction Without Reserve in cooperation with Bruce Garber, Joe Steger, and Roger St Clair of Century 21 BHJ Realty, Inc. Bidding, which will be held via Concierge Auctions’ online marketplace, will open July 23rd and close July 26th. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190624005652/en/ Holy Cow Ranch – Sheridan, WY (Photo: Business Wire) “The auction of Holy Cow Ranch presents the opportunity to own a truly impressive range of some of North America’s most beautiful landscapes,
Avioq Announces CE Mark and European Launch of VioOne HIV Profile Supplemental Assay24.6.2019 15:11:00 CEST | Pressemelding
Avioq, Inc. has received CE Marking (Conformité Européenne) and has begun marketing their VioOne™ HIV Profile™ Supplemental Assay in the European Union and other CE Mark countries. The product has also been submitted for FDA approval. “We are pleased to provide the CE Mark HIV Profile™ assay to countries outside the U.S.,” said Chamroen Chetty, CEO of Avioq. Dr. Chetty continues, “We are also looking for distribution partners to expand the global availability.” The HIV Profile™ is an enzyme-linked immunosorbent assay (ELISA) for confirmation and differentiation of individual antibodies directed to various gene products of HIV-1 (Group M & Group O) and HIV-2 in human serum or plasma that were repeatedly reactive in diagnostic screening procedures. Results can also be used to distinguish recent from longstanding HIV-1 infection for HIV-1 incidence estimation. About Confirmatory Testing In 2014, the CDC released a new algorithm for HIV testing. The second step of the algorithm includes a
Global Launch of S BLOCK, Kicked Off in Singapore on June 22nd24.6.2019 12:29:00 CEST | Pressemelding
The globally renowned 2019 WBF Singapore Technology Conference was held in Marina Bay Sands Hotel on June 22nd, 2019. S BLOCK, the conference co-host, unveiled itself and announce its mission to “Unleash your digital assets” for the first time. The conference brought together numerous industry elites and blockchain enthusiasts from all around the world, including more than 500 industry veterans from over 30 countries, such as Switzerland, Germany, France, Russia, Japan, Korea, Brazil, Australia, Argentina and Canada. Insiders shared profound global industry insights. This conference draws great attention from across the global blockchain industry. S BLOCK Kicked Off in Singapore In the morning of June 22nd, Ivan - President of S BLOCK Global Foundation, was invited to deliver a keynote speech, “Next Generation Digital Currency Wallet”. At this conference, S BLOCK was officially launched in more than 30 countries around the world, and opened up the way to a global future without borders