OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved ADZYNMA (ADAMTS13, recombinant-krhn) for the prophylactic and on-demand treatment of adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).

大阪，日本和剑桥，马萨诸塞州-（商业电线）-武田（TSE:4502/NYSE:TAK）今天宣布美国食品和药物管理局（FDA）已批准ADZYNMA（ADAMTS13，重组krhn）用于预防和按需治疗成人和儿童先天性血栓性血小板减少性紫癜（cTTP）患者。

ADZYNMA is the first and only FDA-approved recombinant ADAMTS13 (rADAMTS13) protein designed to address an unmet medical need in people with cTTP by replacing the deficient ADAMTS13 enzyme.1,2.

ADZYNMA是第一个也是唯一一个FDA批准的重组ADAMTS13（rADAMTS13）蛋白，旨在通过替换缺陷的ADAMTS13酶来解决cTTP患者未满足的医疗需求。

“People living with cTTP face serious, life-threatening health challenges, and until today, were without any approved treatment specifically indicated for their disease,” said Julie Kim, president, U.S. Business Unit and U.S. country head at Takeda. “As we strive to help patients with limited or no treatment options, developing innovative treatments in rare diseases is an inspiring challenge and one we have taken on for 70-plus years as a leader in hematology.

美国商业部门总裁兼美国武田县国家主管朱丽叶·金（Julie Kim）说：“患有cTTP的人面临严重的威胁生命的健康挑战，直到今天，还没有任何针对其疾病的明确治疗。“当我们努力帮助治疗方案有限或没有治疗方案的患者时，开发罕见疾病的创新治疗方法是一个鼓舞人心的挑战，我们已经在血液学领域占据了70多年的领先地位。

Today, we are proud to further support the rare disease community by delivering ADZYNMA as the first FDA-approved therapeutic option for people with cTTP.”.

今天，我们很自豪通过提供ADZYNMA作为FDA批准的cTTP患者的首个治疗选择，进一步支持罕见疾病社区。

cTTP is an ultra-rare, chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme.3 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.3,4,5 When left untreated, acute TTP events have a mortality rate of >90%.3,5.

cTTP是由ADAMTS13酶缺乏引起的超罕见的慢性凝血障碍[3]。它与急性事件和使人衰弱的慢性症状或血栓性血小板减少性紫癜（TTP）表现相关，其可包括血小板减少症，微血管病性溶血性贫血，头痛和腹痛3,4,5如果不及时治疗，急性TTP事件的死亡率>90%.3,5。

“In recent decades, significant progress has been made to better understand the link between ADAMTS13 deficiency and cTTP, ultimately leading to this moment where we finally have an FDA-approved treatment option for patients living with this rare disease,” said Spero R. Cataland, M.D., professor of internal medicine at the Wexner Medical Center at The Ohio State University, co-director at the U.S.

俄亥俄州立大学韦克斯纳医学中心内科教授Spero R.Cataland博士说：“近几十年来，为了更好地理解ADAMTS13缺乏症和cTTP之间的联系，取得了重大进展，最终导致了这一时刻，我们最终得到了FDA批准的治疗选择，美国联合董事。

Thrombotic Microangiopathy Alliance (USTMA) and ADZYNMA clinical trial investigator. “ADZYNMA provides patients with a treatment option that replaces their deficient ADAMTS13 enzyme and offers a favorable efficacy and safety profile and reduced administration time and volume compared to current plasma-based therapies.

血栓性微血管病联盟（USTMA）和ADZYNMA临床试验研究员。“与目前基于血浆的疗法相比，ADZYNMA为患者提供了一种治疗选择，可替代其不足的ADAMTS13酶，并提供良好的疗效和安全性，并减少给药时间和体积。

Today marks a significant achievement, providing new possibilities for the cTTP patient community.”.

今天标志着重大成就，为cTTP患者社区提供了新的可能性。”。

The FDA approval of ADZYNMA was supported by the totality of the evidence provided by the analysis of efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled, open-label, crossover Phase 3 trial in cTTP as well as by data from the continuation trial. 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).1.

FDA批准ADZYNMA得到了cTTP第一个随机，对照，开放标签，交叉3期试验的疗效，药代动力学，安全性和耐受性数据分析所提供的全部证据以及来自延续审判。在3期试验中，患者每隔一周或每周接受40 IU/kg ADZYNMA IV或基于血浆的治疗，基于入组时的方案1-6个月（第1期），转换为替代治疗7-12个月（第2期），所有患者在第13-18个月（第3期）接受ADZYNMA治疗。

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).1 No subacute TTP events were reported in patients receiving ADZYNMA during the Phase 3 study-controlled comparison periods 1 and 2, compared to five subacute TTP events in four patients receiving plasma-based therapies.

没有患者在接受ADZYNMA预防性治疗时发生急性TTP事件（n=37），而接受基于血浆的治疗的患者发生一次急性TTP事件（n=38）.1接受ADZYNMA的患者未报告亚急性TTP事件在第3阶段研究控制的比较阶段1和2期间，与接受基于血浆的疗法的四名患者中的五个亚急性TTP事件相比。

In the continuation period (period 3), two patients receiving ADZYNMA prophylaxis had two subacute events.1.

在持续期间（第3阶段），两名接受ADZYNMA预防的患者发生了两次亚急性事件。

The mean annualized event rate (SD) of thrombocytopenia manifestations was 2.0 (4.706) for patients receiving ADZYNMA (9/37 patients experienced a manifestation) compared to 4.44 (6.312) in patients receiving plasma-based therapies (19/38 patients experienced a manifestation).1 While the clinical significance of the comparison is unknown, thrombocytopenia is a manifestation of TTP, and as such is an important biomarker of disease activity..

接受ADZYNMA治疗的患者（9/37患者有表现）血小板减少症表现的平均年化事件发生率（SD）为2.0（4.706），而接受血浆治疗的患者（19/38患者有表现）为4.44（6.312）。虽然比较的临床意义尚不清楚，但血小板减少症是TTP的一种表现，因此是疾病活动的重要生物标志物。。

ADZYNMA is a recombinant form of the ADAMTS13 protein. In a pharmacokinetic assessment, patients receiving 40 IU/kg ADZYNMA IV (n=23) achieved a four- to five-fold increase in ADAMTS13 activity following a single infusion compared to plasma-based therapies.1

ADZYNMA是ADAMTS13蛋白的重组形式。在药代动力学评估中，与基于血浆的疗法相比，单次输注后接受40 IU/kg ADZYNMA IV（n=23）的患者ADAMTS13活性增加了4至5倍

ADZYNMA demonstrated a favorable safety profile compared to plasma-based therapies. The most common adverse reactions (incidence >5%) were headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting.1 No patients receiving ADZYNMA developed neutralizing antibodies.1.

与基于血浆的疗法相比，ADZYNMA表现出有利的安全性。最常见的不良反应（发生率>5%）为头痛，腹泻，偏头痛，腹痛，恶心，上呼吸道感染，头晕和呕吐.1没有接受ADZYNMA治疗的患者出现中和抗体。

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

本批准不会导致截至2024年3月31日（2023财年）的武田综合预测发生任何变化。

ABOUT ADZYNMA

关于ADZYNMA

ADZYNMA (ADAMTS13, recombinant-krhn) is a human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” ADAMTS13 (rADAMTS13) indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).1.

ADZYNMA（ADAMTS13，重组krhn）是一种人重组“a解聚素和金属蛋白酶与血小板反应蛋白基序13”ADAMTS13（rADAMTS13），适用于成人和儿童先天性血栓性血小板减少性紫癜患者的预防性或按需酶替代疗法（ERT）（cTTP）.1。

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, 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先前被美国FDA授予孤儿药名称（ODD），用于治疗和预防TTP，包括其获得性特发性和继发性形式，以及快速和罕见的儿科疾病名称。美国FDA授予武田罕见的儿科疾病凭证，以批准ADZYNMA。

ADZYNMA has also been granted ODD by the European Medicines Agency (EMA) and Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of TTP..

欧洲药品管理局（EMA）和日本厚生劳动省（MHLW）也批准ADZYNMA用于治疗TTP。。

Important Safety Information

重要的安全信息

ADZYNMA is contraindicated in patients who have experienced life-threatening hypersensitivity reactions to ADZYNMA or its components.

ADZYNMA禁用于对ADZYNMA或其成分发生危及生命的超敏反应的患者。

Hypersensitivity Reactions: Allergic-type hypersensitivity, including anaphylactic reactions, may occur with ADZYNMA. 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.

超敏反应：ADZYNMA可能发生过敏型超敏反应，包括过敏反应。应教育患者有关过敏的早期迹象，如心动过速，胸闷，喘息和/或急性呼吸窘迫，低血压，全身性荨麻疹，瘙痒，鼻结膜炎，血管性水肿，嗜睡，恶心，呕吐，感觉异常和烦躁不安。

If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care..

如果出现严重过敏反应的体征和症状，立即停止给予ADZYNMA并提供适当的支持治疗。。

Immunogenicity: There is a potential for immunogenicity with ADZYNMA. 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.

免疫原性：ADZYNMA具有免疫原性的潜力。患者可能会产生针对ADAMTS13的中和抗体，这可能会导致对ADAMTS13的反应降低或缺乏。患者可能会产生针对宿主细胞蛋白的抗体，这可能会导致不良反应。

There are no data on immunogenicity with ADZYNMA or to host cell proteins in previously untreated patients (subjects naïve to plasma-based products)..

没有关于ADZYNMA或宿主细胞蛋白在先前未治疗的患者中的免疫原性的数据（对基于血浆的产品幼稚的受试者）。。

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

不良反应：与ADZYNMA相关的最常见不良反应（>5%的受试者）是头痛，腹泻，偏头痛，腹痛，恶心，上呼吸道感染，头晕和呕吐。

Use in Specific Populations: The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data are insufficient to inform a drug associated risk of adverse developmental outcomes. There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production, or the breastfed infant..

在特定人群中使用：ADZYNMA在妊娠期间使用的安全性尚未在对照临床试验中确定。有限的数据不足以告知药物相关的不良发育结果风险。没有关于人乳中ADZYNMA的存在，其对产奶量或母乳喂养婴儿的影响的信息。。

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 www.fda.gov/medwatch.

要报告疑似不良反应，请致电1-877-Takeda-7（1-877-825-3327）联系Takeda Pharmaceuticals U.S.A，Inc。或致电1-800-FDA-1088或www.FDA.gov/medwatch联系FDA。

Please see full Prescribing Information, including information for patients.

请参阅完整的处方信息，包括患者信息。

ABOUT cTTP

关于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 TTP has an estimated prevalence of 2-6 cases/million. The inherited form of the disease, cTTP, accounts for ≤5% of TTP patients.7,8,9 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.4,7 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).4.

cTTP是一种极其罕见的慢性和衰弱性凝血障碍，与危及生命的急性事件和衰弱的慢性症状或TTP表现相关.6,7 TTP估计患病率为2-6例/百万。该病的遗传形式cTTP占TTP患者的≤5%。7,8,9由于缺乏von Willebrand因子（VWF）裂解蛋白酶ADAMTS13而发展，这导致超大VWF多聚体在血液中积聚[6]。超大VWF多聚体的积聚导致血小板聚集和粘附不受控制[4,7]。这可能导致身体小血管凝血异常，与微血管性溶血性贫血和低血小板水平（血小板减少症）有关。

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%.3,10 cTTP can also cause ongoing widespread organ damage and other co-morbidities resulting from an ADAMTS13-deficient state.5,7,10,11

cTTP具有急性和慢性表现（包括中风和心血管疾病），如果不及时治疗，急性TTP事件的死亡率>90%[3,10].cTTP还可能导致持续广泛的器官损伤和其他合并症ADAMTS13缺陷状态5,7,10,11

About Takeda

关于武田

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.

武田专注于为人们创造更好的健康和更光明的世界未来。我们的目标是在我们的核心治疗和商业领域发现并提供改变生命的治疗方法，包括胃肠道和炎症，罕见疾病，血浆衍生疗法，肿瘤学，神经科学和疫苗。

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.

与我们的合作伙伴一起，我们的目标是通过我们动态多样的渠道改善患者体验并推进治疗方案的新前沿。作为总部设在日本的领先价值型研发型生物制药公司，我们以对患者，人民和地球的承诺为指导。

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..

我们在大约80个国家和地区的员工都是以我们的目标为动力，并以定义我们两个多世纪的价值观为基础。欲了解更多信息，请访问www.takeda.com。。

For the purposes of this notice, “press release” means this document, any oral presentation, any question-and-answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction.

就本通知而言，“新闻稿”是指本文档，任何口头陈述，任何问答会议以及武田制药有限公司（“Takeda”）就本版本讨论或分发的任何书面或口头材料。本新闻稿（包括任何口头简报以及与之相关的任何问答）并非旨在，也不构成，代表或构成任何报价，邀请或征求任何购买，以其他方式获取，订阅的报价的一部分。，交换，出售或以其他方式处置任何证券或在任何司法管辖区征集任何投票或批准。

No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. 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).

本新闻稿不会向公众提供股份或其他证券。除非根据1933年“美国证券法”（经修订）进行注册或免除，否则不得在美国提供证券。本新闻稿正在提供（连同可能提供给收件人的任何进一步信息），前提是收件人仅用于信息目的（而不是用于评估任何投资，收购，处置或任何其他交易）。

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.

任何不遵守这些限制可能构成违反适用证券法。武田直接和间接拥有投资的公司是独立的实体。在本新闻稿中，为了方便起见，有时会使用“武田”来引用武田及其子公司。

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..

同样，“我们”，“我们”和“我们”这两个词也被用来指一般的子公司或为其工作的子公司。这些表达式也用于通过识别特定公司或公司而无法达到有用目的的情况。。

Forward-Looking Statements

前瞻性声明

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”, “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof.

本新闻稿和与本新闻稿相关的任何材料可能包含有关武田未来业务，未来立场和运营结果的前瞻性陈述，信念或意见，包括武田的估计，预测，目标和计划。不受限制，前瞻性陈述通常包括诸如“目标”，“计划”，“相信”，“希望”，“继续”，“期望”，“目标”，“意图”，“确保”，“将会”，“可能”，“应该”，“将会”，“可以”，“预期”，“估计”，“项目”或其负面表达。

These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to div.

这些前瞻性声明基于对许多重要因素的假设，包括以下因素，这可能导致实际结果与前瞻性声明所表达或暗示的结果大不相同：武田全球业务的经济状况，包括一般经济状况在日本和美国；竞争压力和发展；适用法律法规的变化，包括全球卫生保健改革；新产品开发固有的挑战，包括临床成功的不确定性和监管机构的决定及其时机；新产品和现有产品商业成功的不确定性；制造困难或延误；利息和货币汇率波动；关于市售产品或候选产品的安全性或有效性的声明或担忧；像新型冠状病毒大流行这样的健康危机对武田及其客户和供应商（包括武田经营国家的外国政府）或其业务其他方面的影响；合并后整合工作与收购公司的时机和影响；div的能力。

Medical Information

医学情报室

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..

本新闻稿包含有关产品的信息，这些产品可能并非在所有国家/地区提供，或可能以不同商标，不同适应症，不同剂量或不同优势提供。这里所包含的任何内容都不应被视为任何处方药（包括正在开发的处方药）的征求，促销或广告。。

ADZYNMA is a trademark of Takeda Pharmaceuticals International AG.

ADZYNMA是武田制药国际公司的商标。

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1 ADZYNMA (ADAMTS13, recombinant-krhn) Prescribing Information; 2023.

1 ADZYNMA（ADAMTS13，重组krhn）处方信息；2023.

2Scully M et al. Blood. 2017; 130:2055-63

2Scully M等人，Blood。2017年；130:2055-63

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