cTTP is an Ultra-rare, Potentially Fatal Blood-Clotting Disorder with Limited Treatment Options; Untreated, Acute TTP Events Have a Mortality Rate of >90%1,2

Approval Based on Totality of Evidence, Including Results from the First Randomized, Controlled, Open-label, Crossover Phase 3 cTTP Trial

OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) approved ADZYNMA®▼ (recombinant ADAMTS13) for the treatment of ADAMTS13 deficiency in children and adult patients with congenital thrombotic thrombocytopenic purpura (cTTP).3 ADZYNMA is now the first and only enzyme replacement therapy in the European Union (EU) specifically for the treatment of cTTP.3,4 This approval includes confirmation of orphan medicinal product designation and follows a positive opinion from the Committee for Medicinal Products for Human Use, as announced by the company on May 31, 2024.

cTTP is an ultra-rare, chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme.1 It is associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations, which can include thrombocytopenia, microangiopathic hemolytic anemia, renal manifestations, stroke and abdominal pain.1,2,5 If left untreated, acute TTP events have a mortality rate of >90%.1,2

“A century after the scientific discovery of cTTP, significant unmet needs remain for patients who continue to face life-threatening acute events and debilitating chronic symptoms with limited treatment options,” said Ricardo Marek, President, Europe and Canada Business Unit at Takeda. “This approval marks the first treatment specifically indicated to address the root cause of the disease – ADAMTS13 deficiency. Building on our 70-year legacy of innovation in rare blood disorders, we’re proud to offer ADZYNMA to cTTP patients in the EU and remain committed to bringing innovative medicines to rare disease patients with high unmet need.”

The EC approval was supported by the totality of evidence provided by the interim analysis of efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled open-label, crossover Phase 3 trial in cTTP, as well as safety and efficacy data from the continuation trial. Data from the Phase 3 trial (NCT03393975) were published in The New England Journal of Medicine in May 2024.

In the Phase 3 trial, patients received 40 IU/kg ADZYNMA IV or plasma-based therapy every other week or weekly, based on regimen at enrollment for months 1-6 (period 1), crossing over to the alternate treatment for months 7-12 (period 2), and all patients received ADZYNMA for months 13-18 (period 3).3

No patient experienced an acute TTP event while receiving ADZYNMA prophylactic treatment (n=45), while there was one acute TTP event in a patient receiving plasma-based therapies (n=46).3 One subacute TTP event was reported in one patient receiving ADZYNMA during the controlled comparison periods 1 and 2, compared to seven subacute TTP events in six patients receiving plasma-based therapies.3 In the continuation phase (period 3), efficacy results – incidence rates of acute and subacute TTP events – were consistent with the results from periods 1 and 2.3

ADZYNMA demonstrated a favorable safety profile compared to plasma-based therapies. The most common adverse reactions (incidence >10%) were headache, diarrhea, dizziness, upper respiratory tract infection, nausea and migraine.3

Takeda is investigating recombinant ADAMTS13 in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP), the acquired form of TTP, in an ongoing Phase 2b trial (NCT05714969).

This approval does not result in any changes to Takeda’s consolidated forecast for the fiscal year ending March 31, 2025 (FY2024).

About ADZYNMA
ADZYNMA (recombinant ADAMTS13) is the first and only recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (ADAMTS13) enzyme replacement therapy approved for the treatment of ADAMTS13 deficiency in children and adult patients with cTTP. ADZYNMA is also approved by the U.S. Food and Drug Administration (FDA) and by the Japanese Ministry of Health, Labour, and Welfare (MHLW) for the prophylactic and on-demand treatment of patients with cTTP.

ADZYNMA was granted Orphan Drug Designation (ODD) by the U.S. FDA for the treatment and prevention of TTP, including its acquired idiopathic and secondary forms, as well as Fast Track and Rare Pediatric Disease Designation. The U.S. FDA granted Takeda a Rare Pediatric Disease Voucher for the approval of ADZYNMA. ADZYNMA was also granted ODD by the European Medicines Agency (EMA) and Japanese MHLW for the treatment of TTP.

For the full list of side effects and restrictions with ADZYNMA, see the Product Information.

About cTTP
cTTP is an ultra-rare, chronic and debilitating clotting disorder associated with life-threatening acute events and debilitating chronic symptoms, or TTP manifestations.6,7 Although the exact prevalence of cTTP is unknown, estimates suggest a prevalence of 0.5-2 diagnosed cases/million8 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.6 The accumulation of ultra-large VWF multimers leads to uncontrolled platelet aggregation and adhesion.5,7 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).5

cTTP has both acute and chronic manifestations (including stroke, renal and cardiovascular disease) and when left untreated, acute TTP events have a mortality rate of >90%.1,2,5 cTTP can also cause ongoing widespread organ damage and other co-morbidities resulting from an ADAMTS13-deficient state.2,7,9,10

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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Medical Information
This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

ADZYNMA is a registered trademark of Takeda Pharmaceuticals International AG.

References:

1. Van Dorland H et al. Haematologica. 2019;104:2107-16.
2. Joly BS et al. Blood. 2017;129(21):2836–2846.
3. ADZYNMA (recombinant ADAMTS13) Summary of Product Characteristics; 2024.
4. Scully M et al. Blood. 2017; 130:2055-63.
5. Chiasakul T and Cuker A. Am Soc Hematol. 2018;2018(1):530–538.
6. Alwan F et al. Blood. 2019;133:1644-51.
7. Kremer Hovinga JA et al. Nat Rev Dis Primers. 2017;3:17020.
8. Kremer Hovinga JA and George JN. Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019;381(17):1653-1662.
9. Zheng XL et al. J Thromb Haemost. 2020;18(10):2486-95.
10. Sukumar S et al. J Clin Med. 2021;10:536.