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

As previously reported on December 20, 2019, Takeda Pharmaceutical Company Limited (“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).

The communication from the FDA included queries related to the design and labeling of the SC device. The CRL was unrelated to the clinical safety and efficacy data and conclusions from the pivotal trial supporting the BLA for Entyvio SC. It was also 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 510,000 patient-years of exposure to date.

In August, Takeda had a productive meeting with the FDA to review the Company’s latest data and to seek guidance on additional data needs required to support the approval of Entyvio SC. During the meeting, we gained clarity on data needs for the device, and we are moving forward to address them.

Continued testing of the device will take time, and as a result, we expect to potentially launch Entyvio SC for moderate to severe UC in the United States in 2022, pending FDA approval.

Takeda maintains great confidence in the future of Entyvio SC in the U.S., and strongly believes in the benefit that Entyvio SC can bring to patients who live with moderate to severe UC, pending approval.  We remain committed to working with the FDA to meet patient needs with this important option. Entyvio SC has been approved in Australia, Canada, and Europe, where the product was launched in June 2020; regulatory review is ongoing in Japan, Switzerland and Israel.

 

U.S. INDICATIONS: ENTYVIO (vedolizumab) FOR INTRAVENOUS USE

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.

 

U.S. IMPORTANT SAFETY INFORMATION FOR ENTYVIO (VEDOLIZUMAB) FOR INTRAVENOUS USE

IMPORTANT SAFETY INFORMATION

• 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 cells/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.

 

In the U.S., please see the accompanying full Prescribing Information including Medication Guide for ENTYVIO IV.

More information about ENTYVIO IV is available in the U.S. at www.ENTYVIOHCP.com.

 

Media Contacts:
U.S. Media Amy McCarthy [email protected] +1 781-496-7761	Japanese Media Kazumi Kobayashi [email protected] +81 (0) 3-3278-2095	Media outside Japan Luke Willats [email protected] +41-44-555-1145

 

Important Notice

For the purposes of this notice, “release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws.

The companies in which Takeda directly and indirectly owns investments are separate entities. In this release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

 

Forward-Looking Statements

This release and any materials distributed in connection with this release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings-and-security-reports/ or at www.sec.gov. Takeda does not undertake to update any of the forward-looking statements contained in this release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

 

# # #