Update on the U.S. Development Program for the Investigational Subcutaneous Formulation of ENTYVIO® (vedolizumab) as a Maintenance Therapy in Adults with Moderate to Severe Ulcerative Colitis

October 28, 2021

CAMBRIDGE, Massachusetts, October 28, 2021 – As previously reported on December 20, 2019 and updated on September 1, 2020, Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) in response to the submission of a Biologics License Application (BLA) for an investigational subcutaneous (SC) formulation of Entyvio^® (vedolizumab) for maintenance therapy in adults with moderate to severe ulcerative colitis (UC).

Through our ongoing interactions with the FDA, Takeda has received feedback which has provided clarity on the regulatory package and critical elements for the resubmission of the BLA for Entyvio SC as maintenance therapy in adults with moderate to severe ulcerative colitis, and we are moving forward accordingly. We are reviewing our development program timelines and currently anticipate potential approval in FY 2023.

Communications with the FDA have been related to the design and labeling of the SC device and are not related to the clinical safety and efficacy data and conclusions from the pivotal trial supporting the BLA for Entyvio SC. They have also been unrelated to the intravenous (IV) formulation of Entyvio, which has been granted marketing authorization in 71 countries, including the United States and European Union, with more than 740,000 patient-years of exposure to date.¹

Takeda maintains great confidence in the future of Entyvio SC in the U.S. and strongly believes in the benefit it can bring to patients who live with moderate to severe UC. We remain committed to working with the FDA throughout the review and approval process to meet patient needs with this important option. Entyvio SC has been approved in Argentina, Australia, Canada, Kazakhstan, Switzerland, the United Arab Emirates, and Europe, where the product was launched in June 2020.

IMPORTANT SAFETY INFORMATION ENTYVIO Intravenous

ENTYVIO (vedolizumab) for injection is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have been reported. These reactions may occur with the first or subsequent infusions and may vary in their time of onset from during infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice.
Progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported in the post marketing setting (e.g., human immunodeficiency virus [HIV] infection with a CD4 count of 300 cell/mm3 and prior and concomitant immunosuppression). Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.
Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.
Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

Please see accompanying full Prescribing Information, including Medication Guide.

INDICATIONS IV

Adult Ulcerative Colitis (UC)

ENTYVIO (vedolizumab) is indicated in adults for the treatment of moderately to severely active UC.

Adult Crohn’s Disease (CD)

ENTYVIO (vedolizumab) is indicated in adults for the treatment of moderately to severely active CD.

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 discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). 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.

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Media Outside the U.S.
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¹ Takeda data on file (VV-SUP-91507): Vedolizumab Patient Exposure from Marketing Experience. 2021.