Business Wire

European Medicines Agency Accepts Takeda’s Marketing Authorization Application for a Subcutaneous Formulation of Vedolizumab for Maintenance Therapy in Moderately to Severely Active Ulcerative Colitis and Crohn’s Disease

Share

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the European Medicines Agency (EMA) has accepted a Marketing Authorization Line Extension Application for a subcutaneous (SC) formulation of the gut-selective biologic vedolizumab for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). Takeda proposes to make vedolizumab SC available in both pre-filled syringe and pen options.

“This regulatory application marks an important milestone in our continued commitment to delivering innovative medicines and treatment modalities that meet the diverse needs of patients living with ulcerative colitis and Crohn’s disease across Europe,” said Adam Zaeske, Head, GI Franchise, Europe and Canada Business Unit, Takeda. “If approved, a subcutaneous formulation of vedolizumab, together with the currently available intravenous option, will provide greater choice, enhancing the patient experience in line with their treatment preferences and lifestyle.”

The application is based on the pivotal VISIBLE 1 phase 3 study, which assessed the safety and efficacy of a SC formulation of vedolizumab as maintenance therapy in 216 adult patients with moderately to severely active UC who achieved clinical response* at week 6 following two doses of open-label vedolizumab intravenous (IV) induction therapy at weeks 0 and 2.1 Interim data from other ongoing VISIBLE studies involving patients with CD were also included in the application. The results of VISIBLE 1 were presented at the 2018 United European Gastroenterology (UEG) Week Congress in Vienna, Austria.

In evaluating the primary endpoint of VISIBLE 1, a statistically significant proportion of patients receiving vedolizumab SC 108 mg maintenance therapy administered every two weeks achieved clinical remission** compared to patients receiving placebo (46.2% vs. 14.3%; p<0.001) at week 52. A similar rate of clinical remission was observed in the vedolizumab IV 300 mg reference arm (42.6%) at week 52. Furthermore, adverse event rates, including severe adverse events and infections, were similar between the SC and IV groups at week 52. Injection-site reactions were mild and experienced by 10.4% of patients in the vedolizumab SC treatment arm (vs. 0% in the placebo group), with none leading to treatment discontinuation.1

* 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 point2
** Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore >1 point2

###

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.2,3,4

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).5 Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract that are often progressive in nature.6,7 UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus.8,9 CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine.8 UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus.8,10 CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.6 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. 8,11,12

About Entyvio ® (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.13 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).14 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.15 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.14 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).14,16,17 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.14

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.13 Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 260,000 patient years of exposure to date.18

Therapeutic Indications (vedolizumab IV)

Ulcerative colitis
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.

Crohn’s disease
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

Contraindications
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 prepared 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 patients during infusion and until the infusion is complete.

Infusion-related reactions
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.

Infections
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 specific to 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. 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.

Malignancies
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. 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.

Vaccinations
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, fatigue and anaphylaxis.

Please consult with your local regulatory agency for approved labeling in your country.

For U.S. audiences, please see the full  Prescribing Information  including  Medication Guide  for ENTYVIO ® .

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/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience, and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.

For more information, visit https://www.takeda.com

References

1 Sandborn WJ, Baert F, Danese S, et al. Efficacy and safety of a new vedolizumab subcutaneous formulation for ulcerative colitis: results of the VISIBLE 1 phase 3 trial. United European Gastroenterology J. 2018;6(Supplement 1).

2 Efficacy and safety of vedolizumab subcutaneously (SC) as maintenance therapy in ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02611830. Last updated: August 27, 2018. Last accessed March 2019.

3 Efficacy and safety of vedolizumab subcutaneous (SC) as maintenance therapy in Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02611817. Last updated: December 24, 2018. Last accessed March 2019.

4 Vedolizumab subcutaneous long-term open-label extension study. Available at: https://clinicaltrials.gov/ct2/show/NCT02620046. Last updated December 24, 2018. Last accessed March 2019.

5 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
6 Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590-1605.
7 Torres J, Billioud V, Sachar DB, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18:1356-1363.
8 Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380:1606-1619.

9 Feuerstein JD, Cheifetz AS. Crohn’s disease: Epidemiology, diagnosis and management. Mayo Clin Proc. 2017;92:1088-1103.

10 Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126:1518-1532.
11 Henckaerts L, Pierik M, Joossens M, et al. Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease. Gut. 2007;56:1536-1542.
12 Kaser A, Zeissig S, Blumberg RS. Genes and environment: How will our concepts on the pathophysiology of IBD develop in the future? Dig Dis. 2010;28:395-405.

13 European Medicines Agency. Entyvio EPAR product information. EMEA/H/C/002782 - IB/0030 ANNEX 1 Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/entyvio-epar-product-information_en.pdf. Last updated: December 12, 2018. Last accessed: March 2019.

14 Soler D, Chapman T, Yang LL, et al. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864-875.
15 Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151:97-110.
16 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298-1312.
17 Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis. 2016;10:1437-1444.
18 Takeda Data on File. 2019.

Contact information

Media Contacts:
Media outside Japan
Luke Willats
luke.willats@takeda.com
+41-44-555-1145

Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095

About Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

FDA Approves OTEZLA® (apremilast) for the Treatment of Oral Ulcers Associated with Behçet’s Disease19.7.2019 17:59:00 CESTPress release

Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has approved OTEZLA® (apremilast) 30 mg twice daily (BID) for the treatment of adult patients with oral ulcers associated with Behçet’s Disease. OTEZLA, an oral, selective inhibitor of phosphodiesterase 4 (PDE4), is the first and only approved treatment option for oral ulcers associated with Behçet’s Disease, a rare, chronic, multisystem inflammatory disease that is difficult to treat. “Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s Disease, and have an important negative impact on the quality of life for these patients,” said Yusuf Yazici, M.D., Clinical Associate Professor, Department of Medicine, New York University Langone Health. “In the clinical trial, OTEZLA demonstrated improvements in measures of oral ulcers at week 12. OTEZLA has the potential to be a needed treatment option for U.S. patients and their physicians, who

Abiraterone Acetate Included in World Health Organisation’s Essential Medicines List for the Treatment of Metastatic Castration-Resistant Prostate Cancer19.7.2019 13:05:00 CESTPress release

The Janssen Pharmaceutical Companies of Johnson & Johnson is delighted with the recent announcement from the World Health Organisation (WHO) to include abiraterone acetate (ZYTIGA ® ) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), in the updated Essential Medicines List, published on 9th July 2019.1,2 The WHO’s Essential Medicines List is a core guidance document that helps countries prioritise critical health products that are recommended to be widely available and affordable throughout health systems.1 “The inclusion of abiraterone acetate in the WHO Essential Medicines List highlights the critical role that this treatment can play in improving the lives of patients living with mCRPC and their families,” said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. “I am proud that we are working hard to impact survival and quality of life by developing and providing innovative medicines which ar

Gilead Sciences Licenses Respiratory and Herpes Antiviral Research Programs From Novartis19.7.2019 12:30:00 CESTPress release

Gilead Sciences, Inc. (NASDAQ: GILD) announced today that it has licensed three preclinical antiviral programs from Novartis, including investigational agents with the potential to treat human rhinovirus, influenza and herpes viruses. Under the agreement, Gilead will acquire exclusive global rights to develop and commercialize novel small molecules against three undisclosed targets. Novartis will receive an upfront payment and is eligible to receive up to an additional $291 million in potential milestone payments upon achievement of certain development and commercial milestones, as well as royalties on annual net sales. “Today’s announcement builds on Gilead’s heritage in antiviral research and development. We look forward to applying this expertise to advance the development of potential new treatments for viruses with limited therapeutic options,” said John McHutchison AO, MD, Gilead’s Chief Scientific Officer and Head of Research and Development. Gilead’s antiviral portfolio include

Schlumberger Announces Second-Quarter 2019 Results19.7.2019 11:00:00 CESTPress release

Schlumberger Limited (NYSE: SLB) today reported results for the second quarter of 2019. (Stated in millions, except per share amounts) Three Months Ended Change Jun. 30, 2019 Mar. 31, 2019 Jun. 30, 2018 Sequential Year-on-year Revenue $8,269 $7,879 $8,303 5% 0% Pretax segment operating income $968 $908 $1,094 7% -12% Pretax segment operating margin 11.7% 11.5% 13.2% 17 bps -148 bps Net income - GAAP basis $492 $421 $430 17% 14% Net income, excluding charges & credits* $492 $421 $594 17% -17% Diluted EPS - GAAP basis $0.35 $0.30 $0.31 17% 13% Diluted EPS, excluding charges & credits* $0.35 $0.30 $0.43 17% -19% North America revenue $2,801 $2,738 $3,139 2% -11% International revenue $5,463 $5,037 $5,065 8% 8% North America revenue, excluding Cameron $2,243 $2,178 $2,546 3% -12% International revenue, excluding Cameron $4,761 $4,469 $4,387 7% 9% *These are non-GAAP financial measures. See section titled "Charges & Credits" for details. Schlumberger Chairman and CEO Paal Kibsgaard commente

Schlumberger Appoints Olivier Le Peuch as CEO19.7.2019 10:46:00 CESTPress release

Schlumberger Limited (NYSE: SLB) announced today that its Board of Directors has appointed Olivier Le Peuch as its Chief Executive Officer and member of the Schlumberger Board, effective August 1, 2019. Mr. Le Peuch succeeds Paal Kibsgaard, who will retire as Chief Executive Officer effective that same date. Also effective August 1, Mr. Kibsgaard will step down as Chairman of the Board and retire as a member of the Board of Directors. Mr. Kibsgaard will retire after more than 22 years of service to the Company, including eight years as CEO and four years as Chairman. Effective the same date, Mark G. Papa, a current non-independent director, will become non-executive Chairman of the Board. Peter Currie will continue to serve as the Board’s Lead Independent Director. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190719005161/en/ Olivier Le Peuch is appointed Chief Executive Officer and a member of the Schlumberger Board, effe

Fluke Corporation Acquires Industrial Reliability Leader PRÜFTECHNIK19.7.2019 10:00:00 CESTPress release

Fluke Corp., the global leader in test and measurement instruments, has acquired Ismaning, Germany-based PRÜFTECHNIK, a market leader in precision laser shaft alignment, condition monitoring, and non-destructive testing. “Fluke’s acquisition of PRÜFTECHNIK reflects the growing importance our customers place on reliability systems to keep their equipment in optimum operating condition,” said Marc Tremblay, president of Fluke Corporation. “This business will help us usher in the next generation of solutions for our industrial customers.” Fluke Corporation For information on Fluke tools and applications, or to find the location of your nearest distributor, contact Fluke Corporation, P.O. Box 9090, Everett, WA USA 98206, call (800) 44-FLUKE (800-443-5853), fax (425) 446-5116, e-mail fluke-info@fluke.com or visit the Fluke Web site at http://www.fluke.com. About Fluke Founded in 1948, Fluke Corporation is the world leader in compact, professional electronic test tools and software for measu