U.S. FDA Accepts Takeda's Application for Intravenous ENTYVIO® (vedolizumab) in Pediatric Ulcerative Colitis and Crohn's Disease

• If approved, ENTYVIO would be the only gut-focused treatment for patients two years and older with moderately to severely active ulcerative colitis (UC) or Crohn's disease
• Potential for ENTYVIO to address pediatric treatment gaps, reflecting Takeda's commitment to advancing options where unmet treatment needs remain

Takeda ((TAK) today announced the U.S. Food and Drug Administration (FDA) has accepted for review its supplemental Biologics License Application (sBLA) for intravenous (IV) ENTYVIO^® (vedolizumab) for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn's disease in pediatric patients ages 2 years and older. If approved, ENTYVIO would be the only gut-focused treatment option for these patients. This milestone reflects Takeda's deep commitment to this patient community and its role in advancing care and addressing unmet needs in UC and Crohn's. The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date in the first quarter of calendar year 2027.

"A child or teen diagnosed today with UC or Crohn's disease has decades of medical treatment ahead and represents one of the most challenging to treat patient populations in pediatric gastroenterology. Yet, historically, therapeutic options for this age group have been limited," said Chinwe Ukomadu, MD, PhD, senior vice president and head, Gastrointestinal & Inflammation Therapeutic Area Unit. "There is a need for additional treatments that can achieve clinical remission. The efficacy and safety profile of ENTYVIO is well-established in adults with more than a dozen years of scientific study and clinical data. We're confident that, if approved, ENTYVIO IV would contribute to addressing the unmet needs in the treatment of pediatric UC and Crohn's disease."

UC and Crohn's disease, the two most common forms of inflammatory bowel disease (IBD),¹ are lifelong, relapsing, remitting, inflammatory diseases of the gastrointestinal tract.^2,3 In approximately 25 percent of patients, IBD is diagnosed before age 20, and its prevalence among children and adolescents around the world continues to rise.^4,5 Children with IBD often develop more extensive disease compared to their adult counterparts.⁶ Takeda is committed to supporting this vulnerable patient population with evidence-based therapies.

Takeda has also submitted a marketing authorization application (MAA) to the European Medicines Agency for ENTYVIO IV for the treatment of moderately to severely active UC and Crohn's disease in pediatric patients ages 2 years and older, and plans to submit applications in additional markets later this year. The sBLA and MAA are supported by data from two randomized, double-blind, multicenter Phase 3 pediatric trials in patients ages 2 to 17 years—the KEPLER study (NCT: 04779307; EudraCT: 2020-004300-34) in UC and the ongoing WEBB study (NCT: 04779320; EudraCT: 2020-004301-31) in Crohn's disease. The primary endpoint for KEPLER was clinical remission at Week 54 among patients who achieved a clinical response following vedolizumab IV induction, while WEBB had co-primary endpoints of clinical remission and endoscopic response at Week 54.^7,8

ENTYVIO is currently approved for the treatment of moderately to severely active UC and Crohn's disease in adults.

About ENTYVIO^® (vedolizumab)

ENTYVIO, a biologic therapy, is the only gut-focused treatment available for ulcerative colitis and Crohn's disease in adults. It specifically binds to the α4β7 integrin and blocks its interaction with MAdCAM-1, which is mainly expressed on the gut endothelial cells.⁹ ENTYVIO is approved for IV and subcutaneous (SC) administration in adults with moderately to severely active ulcerative colitis and 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 (approvals vary by market).^10,11 Marketing authorization has been granted in more than 80 countries for ENTYVIO IV and in more than 50 countries for ENTYVIO SC. Globally, ENTYVIO IV and SC have more than 1.9 million patient years of exposure to date.¹²

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.

WARNINGS AND PRECAUTIONS

• Infusion-Related and Hypersensitivity Reactions: 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.
  
  
  
  
• Infections: ENTYVIO increases the risk for developing infections. Serious infections in clinical trials included anal abscess, sepsis (some fatal), tuberculosis (TB), salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. Postmarketing reports include systemic bacterial, fungal, viral, and parasitic opportunistic infections.
  
  
  
  Do not start ENTYVIO in patients with a clinically important active infection until resolved or adequately treated. In patients with chronic infection or history of recurrent infection, consider risks and benefits prior to ENTYVIO. Instruct patients to seek medical advice if signs or symptoms of acute or chronic infection occur. If a serious infection develops or does not respond to therapy, monitor closely and do not administer ENTYVIO until resolved.
  
  
  
  Tuberculosis: Consider evaluating for TB prior to ENTYVIO. Do not administer ENTYVIO to patients with active TB. Before starting ENTYVIO, treat latent TB and consider anti-TB therapy in patients with a history of TB if adequate course of treatment cannot be confirmed. Monitor for active TB during and after ENTYVIO.

• Progressive Multifocal Leukoencephalopathy (PML): 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 typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported. Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms that may 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 neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
  
  
  
  
• Liver Injury: 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.
  
  
  
  
• Immunizations: 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.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥3% and ≥1% higher than placebo) were: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, pain in extremities, and injection site reactions with subcutaneous administration.

DRUG INTERACTIONS

Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab products and with TNF blockers. Upon initiation or discontinuation of ENTYVIO in patients treated with CYP450 substrates, monitor drug concentrations or other therapeutic parameters, and adjust the dosage of the CYP substrate as needed.

INDICATIONS

ENTYVIO is indicated in adults for the treatment of:

• Moderately to severely active ulcerative colitis (UC)
• Moderately to severely active Crohn's disease (CD)

DOSAGE FORMS & STRENGTHS:

• ENTYVIO Intravenous (IV) Infusion: 300 mg vedolizumab
• ENTYVIO Subcutaneous (SC) Injection: 108 mg vedolizumab

Please click for Full U.S. Prescribing Information.

About Takeda

Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

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