- Key learnings from real-world data and retrospective studies from nine abstracts are presented at the 62^nd ASH Annual Meeting & Exposition, taking place virtually this year

- Takeda continues to gather and apply real-world evidence in the treatment of hemophilia, von Willebrand disease (VWD) and sickle cell disease (SCD) and advance personalized treatment in its ongoing commitment to people living with bleeding disorders

CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) (�Takeda�), today presented five hematology poster presentations and four abstracts at the 62^nd American Society of Hematology (ASH) Annual Meeting & Exposition that underscore its commitment to advancing treatments for rare bleeding disorders. Takeda will also be presenting data from its broader oncology portfolio and pipeline at the conference. Read more here.

Real-World Evidence Demonstrates Importance of Patient Centric Care

Real-world evidence (RWE) from studies across rare bleeding disorders demonstrate the crucial role understanding patterns of care and the patient�s holistic experience outside of rigorous clinical studies play in advancing patient-centric treatment in bleeding disorders. Several of Takeda�s studies presented at ASH generate real-world evidence to better understand clinical management of treatment and associated disease outcomes in hemophilia A and VWD.

�Real-world evidence allows healthcare professionals to understand how medications work in routine clinical practice and can advance patient-centric treatment in bleeding disorders,� said Dr. Michael Tarantino, CEO, Chief Medical Officer and President, The Bleeding and Clotting Disorders Institute and Professor of Pediatrics and Medicine at University of Illinois College of Medicine-Peoria. �For example, real world data presented at ASH describe patient satisfaction data with ADYNOVATE. This data help us better understand the true patient experience when using our products.�

Insights generating RWE at ASH 2020 are captured in the following posters:

• ADYNOVATE (Antihemophilic Factor (Recombinant), PEGylated) and Hemophilia A:
  • �ATHN-2: Dosing, Patient Satisfaction and Other Patient-Reported Outcomes after Switching to Rurioctocog Alfa Pegol in ATHN 2: A Longitudinal, Observational Study of Previously Treated Hemophilia Patients Switching Coagulation Replacement Factor Products,� (poster #870) highlights the findings of longitudinally observed patients previously treated with hemophilia A medication switching to rurioctocog alfa pegol to identify dosing regimens, patient satisfaction with the change in therapy, and impact on overall health and productivity.
• ADVATE^� (Antihemophilic Factor (Recombinant)) and Hemophilia A:
  • �Effectiveness and safety outcomes in patients with hemophilia A receiving antihemophilic factor (recombinant) for at least 5 years in a real-world setting: 6-year interim analysis of the AHEAD International and German studies,� (poster #2698) assesses the long-term effectiveness and safety in Hemophilia A (HA) patients treated with ADVATE for greater than five years in a real-world setting.
• FEIBA^� (Anti-Inhibitor Coagulant Complex):
  • �Real-world clinical management of patients with congenital hemophilia and inhibitors: interim analysis of the FEIBA Global Outcome study (FEIBA GO),� (Online publish only) assesses the long-term safety and real-world effectiveness of activated prothrombin complex concentrate as prophylaxis (aPCC) or on-demand treatment seen in FEIBA GO in patients with congenital hemophilia A or B with inhibitors (PwHI) across different clinical settings.
• von Willebrand Disease: Posters featuring data from two studies that aim to advance scientific knowledge and understanding of von Willebrand disease (VWD), including the following retrospective analyses:
  • �Characterization of Hysterectomy in Women with VWD Using Data from a US Medical Claims Database,� (poster #1794) uses medical claims data to assess rates of hysterectomy/UA in women before and after diagnosis of VWD and evaluate hysterectomy/UA (including age at procedure) in women with VWD compared to women without a bleeding disorder.
  • �Retrospective chart review of gastrointestinal bleeding in patients with von Willebrand Disease� (Online publish only) seeks to describe the natural history of treatment and management of GI bleeds in patients with VWD, comparing patients with a history of GI bleeding to those who experienced their first GI bleed within the five years of this chart review.
• Sickle Cell Disease:
  • �Prevalence of vaso-occlusive crises (VOCs) in patients with sickle cell disease: A retrospective US claims database analysis� (Online publish only) is a retrospective database analysis that characterizes the demographic and clinical characteristics of patients with sickle cell disease.

Advancing Personalized Treatment in Bleeding Disorders

In addition to a real-world evidence suite at ASH 2020, Takeda is highlighting its commitment to advancing individualized treatment in rare hematology, by highlighting the importance of a tailored dosing regimen of hemophilia based on patients� different pharmacokinetic (PK) profiles, patient preferences in hemophilia A treatment and patient clinical demographics in sickle cell disease (SCD). For VWD, we are a long way from advancing a PK-guided dosing regimen but are looking at a variety of personal characteristics, such as bodyweight, in order to advance pharmacokinetics in VWD treatment.

�Personalized treatments provide the potential to drive enhanced outcomes while improving both the patient and HCP experience,� comments Wolfhard Erdlenbruch, M.D., PhD, Vice President, Head Global Medical Affairs Hematology. �For rare bleeding disorders, there has been transformative steps around PK modelling to build a more personalized approach to factor therapy, but the journey towards personalization is still being defined, as indicated by this year�s data presented at ASH.�

Additional insights showcased at ASH 2020 include:

• von Willebrand Disease:
  • �Assessment of rVWF pharmacokinetics in overweight and obese VWD patients using a population pharmacokinetic model,� (poster #859) seeks to understand how the relationship between BMI and von Willebrand factor (VWF) pharmacokinetics (PK) in overweight and obese patients could contribute to optimization of dosing in these populations.
• Hemophilia A:
  • �Patient preferences for hemophilia A treatments: A discrete choice experiment,� (poster #1623) measured patients� preferences for different hemophilia A treatments, including emerging treatments such as gene therapy. Results from a survey of patients with moderate or severe hemophilia A and no history of FVIII inhibitors showed that the frequency, route and place of administration and as well as out-of-pocket costs were the treatment attributes with the greatest impact on patient preferences for hemophilia A treatment.
  • �Assessing Patient Experiences with Prophylactic Treatments for Hemophilia A: Concept Elicitation for Gene Therapy,� (Online publish only) attempts to better understand patients� experiences of living with hemophilia A, the impact of traditional hemophilia A treatments, and patients� perceptions of the potential value of gene therapy versus traditional prophylactic treatments.

About ADYNOVATE/ADYNOVI

ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] was first approved by the Food and Drug Administration (FDA) in the U.S. followed by approval in Japan, Canada, and Colombia, and is approved as ADYNOVI^� in the 28 Member States of the European Union (EU) as well as Iceland, Liechtenstein, Norway and Switzerland. In Europe ADYNOVI is approved for the treatment and prophylaxis of bleeding in patients 12 years and above with hemophilia A.

ADYNOVATE Important Information

ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] Important Information

Indications and Limitation of Use

ADYNOVATE is a human antihemophilic factor indicated in children and adults with hemophilia A (congenital factor VIII deficiency) for:

• On-demand treatment and control of bleeding episodes
• Perioperative management
• Routine prophylaxis to reduce the frequency of bleeding episodes

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS

Prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE [Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS

The most common adverse reactions (?1% of subjects) reported in the clinical studies were headache and nausea.

For more information, please refer to the ADYNOVI Summary of Product Characteristics here.

For US specific safety information, please refer to the ADYNOVATE US Prescribing Information here.

ABOUT ADVATE

ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives. ADVATE is approved in the EU for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency) in all age group.

ADVATE is currently approved in over 70 countries worldwide, including the United States, Canada, 28 countries in the European Union, Algeria, Argentina, Australia, Bahrain, Brazil, Brunei, Chile, China, Colombia, Ecuador, GCC, Hong Kong, Iceland, India, Iraq, Israel, Japan, Kazakhstan, Kuwait, Macau, Malaysia, Mexico, Morocco, New Zealand, Norway, Panama, Puerto Rico, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Thailand, Tunisia, Turkey, UAE, Ukraine, Uruguay, Venezuela, Vietnam.

ADVATE Important Information

ADVATE [Antihemophilic Factor (Recombinant)] Important Information

Indications

ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

• Control and prevention of bleeding episodes.
• Perioperative management
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS

Patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & PRECAUTIONS

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE.

Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting. Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies

Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS

• Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII.
• The most common adverse reactions observed in clinical trials (>5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

For more information, please refer to the ADVATE Summary of Product Characteristics here.

For US specific safety information, please refer to the ADVATE US Prescribing Information here.

About VEYVONDI/VONVENDI

VEYVONDI is indicated in adults (age 18 and older) with von Willebrand disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or not indicated for the treatment of hemorrhage and treatment/prevention of surgical bleeding. VEYVONDI should not be used in the treatment of hemophilia A.¹

For full EU Summary of Product Characteristics, including approved indication(s) and important safety information about marketed products, please visit here.

In the US the product has been approved under the trade name VONVENDI^� [von Willebrand factor (Recombinant)] and is indicated for use in adults (age 18 and older) diagnosed with VWD for on-demand treatment and control of bleeding episodes or perioperative management of bleeding.

VONVENDI Important Information

VONVENDI [von Willebrand factor (recombinant)] Important Information

Indications

VONVENDI [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for:

• On-demand treatment and control of bleeding episodes
• Perioperative management of bleeding

Detailed Important Risk Information

CONTRAINDICATIONS

Do not use in patients who have had life-threatening hypersensitivity reactions to VONVENDI or its components (tri-sodium citrate-dihydrate, glycine, mannitol, trehalosedihydrate, polysorbate 80, and hamster or mouse proteins).

WARNINGS AND PRECAUTIONS

Embolism and Thrombosis

Thromboembolic reactions, including disseminated intravascular coagulation, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, can occur, particularly in patients with known risk factors for thrombosis, including low ADAMTS13 levels. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope, and institute prophylaxis measures against thromboembolism based on current recommendations.

In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C activity because sustained excessive factor VIII plasma levels can increase the risk of thromboembolic events.

One out of 80 subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after total hip replacement surgery.

Hypersensitivity Reactions

Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies (Inhibitors)

Inhibitors to VWF and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or antifactory VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD or hemophilia A.

In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.

ADVERSE REACTIONS

In clinical trials, the most common adverse reactions observed in ?2% of subjects (n=80) were generalized pruritus, vomiting, nausea, dizziness, and vertigo. One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.

For more information, please refer to the VEYVONDI Summary of Product Characteristics here.

For US specific safety information, please refer to the VONVENDI US Prescribing Information here.

About FEIBA (Factor VIII Inhibitor Bypassing Activity)

FEIBA^� (factor VIII inhibitor bypassing activity) is indicated for the treatment of spontaneous bleeding and cover of surgical interventions in haemophilia A patients with factor VIII inhibitors and in non-haemophiliacs with acquired factor VIII inhibitors as well as for prophylaxis in haemophilia A patients with high responding inhibitors and frequent joint bleeding.

Please consult the FEIBA Summary of Product Characteristics (SmPC) here before prescribing, particularly in relation to dosing and treatment monitoring.

Contraindications are hypersensitivity to the product, disseminated intravascular coagulation (DIC) and acute thrombosis or embolism (including myocardial infarction).

The Adverse Drug Reactions (ADRs) occurring in the highest frequency (common, greater than or equal to 1/100 to <1/10) were hypersensitivity, headache, dizziness, hypotension, rash, hepatitis B surface antibody positive.

Other symptoms of hypersensitivity reactions to plasma-derived products include lethargy and restlessness.

FEIBA [Anti-Inhibitor Coagulant Complex] Indications and Detailed Important Risk Information

Indications for FEIBA

FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:

• Control and prevention of bleeding episodes
• Perioperative management
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX.

Detailed Important Risk Information for FEIBA

CONTRAINDICATIONS

FEIBA is contraindicated in patients with:

• History of anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system
• Disseminated intravascular coagulation (DIC)
• Acute thrombosis or embolism (including myocardial infarction)

WARNINGS AND PRECAUTIONS

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur, particularly following the administration of high doses (>200 units/kg/day) and/or in patients with thrombotic risk factors.

Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulopathy. Potential benefit of treatment should be weighed against potential risk of these thromboembolic events.

Infusion should not exceed a single dose of 100 units/kg and daily doses of 200 units/kg. Maximum injection or infusion rate must not exceed 2 units/kg/minute. Monitor patients receiving >100 units/kg for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue FEIBA and initiate appropriate diagnostic and therapeutic measures.

Safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established. Cases of thrombotic microangiopathy (TMA) were reported in a clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding following emicizumab treatment. Consider the benefits and risks with FEIBA if considered required for patients receiving emicizumab prophylaxis. If treatment with FEIBA is required for patients receiving emicizumab, the hemophilia treating physician should closely monitor for signs and symptoms of TMA. In FEIBA clinical studies TMA has not been reported.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur. Symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. Reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

FEIBA contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may interfere with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).

ADVERSE REACTIONS

Most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting.

Serious adverse reactions seen are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

DRUG INTERACTIONS

Consider possibility of thrombotic events when systemic antifibrinolytics such as tranexamic acid and aminocaproic acid are used with FEIBA. No adequate and well-controlled studies of combined or sequential use of FEIBA and recombinant factor VIIa, antifibrinolytics, or emicizumab, have been conducted. Use of antifibrinolytics within approximately 6 to 12 hours after FEIBA is not recommended.

Clinical experience from an emicizumab clinical trial suggests that a potential drug interaction may exist with emicizumab.

Contacts

Japanese Media
Kazumi Kobayashi

[email protected]
+81 (0) 3-3278-2095

Media outside Japan
David Murdoch

[email protected]
+1 781-421-1741

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