Purpura, Thrombotic Thrombocytopenic

cTTP is an ultra-rare, life-threatening blood clotting disorder caused by the ADAMTS13 enzyme deficiency. Credit: Kateryna Kon/Shutterstock. The European Commission (EC) has granted approval to Takeda for ADZYNMA (recombinant ADAMTS13) – the first and only enzyme replacement therapy in the European Union (EU) for congenital thrombotic thrombocytopenic purpura (cTTP). cTTP is an ultra-rare, life-threatening blood clotting disorder caused by the ADAMTS13 enzyme deficiency. ADZYNMA is approved to treat ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) deficiency in children and cTTP in adults. The approval follows a positive opinion from the Committee for Medicinal Products for Human Use, announced on 31 May 2024. The EC’s decision was informed by comprehensive data from a Phase III trial and subsequent continuation study, demonstrating the efficacy and safety of ADZYNMA. See Also: Takeda’s ADZYNMA gains EU approval for cTTP treatment Amneal’s CREXONT gains FDA approval for Parkinson’s treatment In the pivotal Phase III trial, 45 patients treated with ADZYNMA did not experience any acute TTP events. One acute event was reported in 46 patients receiving plasma-based therapies. Additionally, one patient experienced a subacute TTP event when treated with ADZYNMA, compared to seven events in six subjects on plasma-based treatments. These findings were consistent in the continuation phase of the trial. ADZYNMA’s safety profile was also favourable when compared to plasma-based therapies, with the most common adverse reactions being diarrhoea, headache, dizziness, nausea, upper respiratory tract infection and migraine. Takeda is further evaluating recombinant ADAMTS13’s potential in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP) in an ongoing Phase IIb trial. ADZYNMA also received approval from the US Food and Drug Administration (FDA) and the Japanese Ministry of Health, Labour and Welfare (MHLW) for the prophylactic and on-demand treatment of cTTP patients. Takeda Europe and Canada Business Unit president Ricardo Marek stated: “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.” In March 2024, Takeda secured approval from the MHLW for ADZYNMA Intravenous Injection 1500 (apadamtase alfa/cinaxadamtase alfa) to treat cTTP.

− 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, MA, USA I August 07, 2024 I 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/million. 8 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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This press 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 press 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. ADZYNMA is a registered trademark of Takeda Pharmaceuticals International AG. References: SOURCE: Takeda Pharmaceutical Co

The European Commission on Tuesday approved Takeda’s ADAMTS13 enzyme replacement therapy (ERT) Adzynma to treat children and adults with congenital thrombotic thrombocytopenic purpura (cTTP), a rare disorder that causes blood clots. The EU clearance, which marks the region’s first ERT approval for cTTP, comes less than a year after the drug received a nod from the FDA.The approval also follows a positive recommendation from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) in May.According to Ricardo Marek, president of Takeda’s Europe and Canada business unit, Adzynma is designed “to address the root cause of the disease,” adding that patients with cTTP “continue to face life-threatening acute events and debilitating chronic symptoms.”Takeda’s ERT is a purified recombinant form of the ADAMTS13 enzyme that works by providing a replacement for low levels of the deficient enzyme in patients with cTTP. It is administered intravenously once every other week for prophylactic ERT to help reduce the risk of disease symptoms, or once daily for on-demand ERT when patients experience an acute event.The approval was based on data from a global Phase III trial during which no patients who received Adzynma experienced an acute TTP event, but one individual in the plasma-based therapy control arm did. Additionally, one patient in the experimental cohort had a subacute TTP event, compared with seven events in six patients who received plasma-based therapy.Adzynma also demonstrated a favourable safety profile versus the comparator, with the most common adverse reactions being mild, such as headache, diarrhoea, dizziness, nausea and migraine.