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Takeda Announces Approval of ADZYNMA® Intravenous Injection 1500 (apadamtase alfa /cinaxadamtase alfa) in Japan for Patients with Congenital Thrombotic Thrombocytopenic Purpura (cTTP)

  • cTTP is an Ultra-rare Blood Clotting Disorder Associated with Life-Threatening Acute Events and Debilitating Chronic Symptoms
  • ADZYNMA (apadamtase alfa /cinaxadamtase alfa) is the First and Only Recombinant ADAMTS13 Enzyme Replacement Therapy for People with cTTP

Takeda (TSE: 4502/NYSE:TAK) today announced that the Japanese Ministry of Health, Labour and Welfare has approved the use of ADZYNMA (apadamtase alfa /cinaxadamtase alfa) for the treatment of congenital thrombotic thrombocytopenic purpura (cTTP) for individuals 12 years of age and older.1 ADZYNMA is the first and only approved recombinant ADAMTS13 protein designed to address an unmet medical need in people with cTTP by replacing the deficient ADAMTS13 enzyme.

cTTP is an ultra-rare, chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme.2 It is associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations, which can include thrombocytopenia, microangiopathic hemolytic anemia, headache and abdominal pain.2,3,4 When left untreated, acute TTP events have a mortality rate of >90%.2,4

“The approval of ADZYNMA is an important milestone for people living with cTTP in Japan, who had limited treatment options and now have the first treatment option specifically approved to treat this ultra-rare condition,” said Yasushi Kajii, Head, R&D Japan Region at Takeda. “Developing innovative treatments that make a difference in the lives of patients is at the heart of what we do. With this approval, we are proud to support the cTTP community with new possibilities and continue our 70-plus year commitment to the rare disease community.”

The approval is supported by the totality of the evidence provided from an interim analysis of efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled, open-label, crossover Phase 3 trial in cTTP patients ages 12-68, (281102 NCT03393975) which includes five Japanese patients and supported by long-term safety and efficacy data from a continuation study (TAK-755-3002 NCT04683003).5 At the time of interim analysis, no patient experienced an acute TTP event while receiving ADZYNMA prophylactic treatment (n=37), while there was one acute TTP event in a patient receiving plasma-based therapies (n=38) during the Phase 3 study-controlled comparison periods 1 and 2.6

Treatment-emergent adverse events (TEAEs) assessed as treatment-related during periods 1 and 2 were reported in 10.3% of patients receiving ADZYNMA compared to 50% of patients receiving plasma-based therapy.6 TEAEs observed in ADZYNMA group were constipation, ADAMTS13 activity abnormal, headache, pruritus, and hypertension (1 subject each). In Period 3, the incidence of TEAEs was 2.8% (1/36) in this drug group: nausea and headache (1 subject each).6

This approval does not result in any changes to Takeda’s consolidated forecast for the fiscal year ending March 31, 2024 (FY2023).

ABOUT ADZYNMA (apadamtase alfa /cinaxadamtase alfa)

ADZYNMA (apadamtase alfa /cinaxadamtase alfa) is a human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” ADAMTS13 (rADAMTS13) indicated for congenital thrombotic thrombocytopenic purpura (cTTP) in Japan.1 ADZYNMA can be used for prophylactic or on-demand enzyme replacement therapy (ERT) in patients 12 years of age and older.

ADZYNMA is also approved by the U.S. Food and Drug Administration (FDA) for the prophylactic and on-demand treatment of adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).7

ADZYNMA was previously granted Orphan Drug Designation (ODD) by the U.S. FDA for the treatment and prevention of TTP, including its acquired idiopathic and secondary forms, and by the European Medicines Agency (EMA) and Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of TTP.

ADZYNMA (apadamtase alfa /cinaxadamtase alfa) Product Overview in Japan

Brand Name

ADZYNMA Intravenous Injection 1500

Generic Name

apadamtase alfa /cinaxadamtase alfa


Congenital thrombotic thrombocytopenic purpura (cTTP)

Dosage and Administration

This drug should be reconstituted with 5 mL of the supplied solvent, and the reconstituted solution should be slowly injected intravenously at a rate of 2~4 mL/min.

For prophylactic treatment

The usual dosage for adults and children aged ≥ 12 years is 40 IU/kg (body weight) every other week. A dose of 40 IU/kg (body weight) may be administered once weekly depending on the dose and regimen of prior therapy or clinical response.

For on-demand treatment

The usual initial dosage for adults and children aged ≥ 12 years is 40 IU/kg (body weight) on Day 1 as the initial dose for measures such as management of thrombotic thrombocytopenic purpura symptoms. Patients will receive 20 IU/kg (body weight) daily on Day 2 and 15 IU/kg (body weight) daily from Day 3 until Day 2 after resolution of symptoms.


cTTP is an ultra-rare, chronic and debilitating clotting disorder associated with life-threatening acute events and debilitating chronic symptoms, or TTP manifestations, which can include thrombocytopenia, microangiopathic hemolytic anemia, headache and abdominal pain.8,9 TTP has an estimated prevalence of 2-6 cases/million, though the true prevalence is unknown. The inherited form of the disease, cTTP, accounts for ≤5% of TTP patients.9,10,11 It develops due to deficiency in ADAMTS13, a von Willebrand factor (VWF) cleaving protease, which results in the accumulation of ultra-large VWF multimers in the blood.8 The accumulation of ultra-large VWF multimers leads to uncontrolled platelet aggregation and adhesion.3,9 This can lead to abnormal clotting in the small blood vessels of the body and is associated with microangiopathic hemolytic anemia and low platelet levels (thrombocytopenia).3

cTTP has both acute and chronic manifestations (including stroke and cardiovascular disease) and when left untreated, acute TTP events have a mortality rate of >90%.3,11 cTTP can also cause ongoing widespread organ damage and other co-morbidities resulting from an ADAMTS13-deficient state.4,9,12,13

Important Safety Information

Apadamtase alfa /cinaxadamtase alfa is contraindicated in patients with a history of hypersensitivity to any of the ingredients of this drug.

Hypersensitivity Reactions: Allergic-type hypersensitivity, including anaphylactic reactions, may occur with apadamtase alfa /cinaxadamtase alfa. Patients should be educated about early signs of hypersensitivity such as tachycardia, chest tightness, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of apadamtase alfa /cinaxadamtase alfa and provide appropriate supportive care.

Immunogenicity: There is a potential for immunogenicity with apadamtase alfa /cinaxadamtase alfa. Patients may develop neutralizing antibodies to ADAMTS13, which could potentially result in a decreased or lack of response to ADAMTS13. Patients may develop antibodies to host cell proteins which could potentially result in adverse reactions. There are no data on immunogenicity with apadamtase alfa /cinaxadamtase alfa or to host cell proteins in previously untreated patients (subjects naïve to plasma-based products).

Adverse Reactions: The most commonly observed adverse reactions (>5% of subjects) associated with apadamtase alfa /cinaxadamtase alfa are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting.

Use in Specific Populations: This drug should be administered to pregnant women or possibly pregnant women only if the expected therapeutic benefits outweigh the possible risks associated with treatment.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or

Please see full Prescribing Information, including information for patients.


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

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Medical information

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  1. ADZYNMA Package Insert in Japan.
  2. Van Dorland H et al. Haematologica. 2019;104:2107-16.
  3. Chiasakul T and Cuker A. Am Soc Hematol. 2018;2018(1):530–538.
  4. Joly BS et al., Blood. 2017;129(21):2836–2846.
  5. A Study of TAK-755 in Participants with Congenital Thrombotic Thrombocytopenic Purpura Available at: Accessed March 2024.
  6. Scully M, et al. Phase 3 prospective, randomized, controlled, open-label, multicenter, crossover study of recombinant ADAMTS13 in patients with congenital thrombotic thrombocytopenic purpura. ISTH 2023 Congress; June 24-28, 2023. Abstract OC 14.1.
  7. ADZYNMA (ADAMTS13, recombinant-krhn) Prescribing Information; 2023.
  8. Alwan F, et al., Blood. 2019;133:1644-51.
  9. Kremer Hovinga JA, et al. Nat Rev Dis Primers. 2017;3:17020.
  10. Kremer Hovinga JA, George JN. Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019;381(17):1653-1662.
  11. Congenital thrombotic thrombocytopenic purpura. Available at: Accessed March 2024.
  12. Zheng XL et al. J Thromb Haemost. 2020;18(10):2486-95.
  13. Sukumar S, et al. J Clin Med. 2021;10:536.


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