LONDON & PLEASANTON, Calif.--(BUSINESS WIRE)--Otsuka Pharmaceutical Europe Ltd. (Otsuka) and Astex Pharmaceuticals, Inc. (Astex) today announce that the European Commission (EC) has approved INAQOVI® (oral decitabine and cedazuridine) as monotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for standard induction chemotherapy.

伦敦和普莱森顿，加利福尼亚州-（商业线）-大冢制药欧洲有限公司（大冢）和Astex制药公司（Astex）今天宣布欧盟委员会（EC）已批准INAQOVI®（口服地西他滨和头孢唑啉）作为单一疗法，用于治疗不符合标准诱导化疗条件的新诊断急性髓性白血病（AML）成人患者。

The EC decision applies to the European Economic Area (EEA), which includes the EU member states, Iceland, Liechtenstein and Norway. INAQOVI® is the first and only oral hypomethylating agent licensed in the EEA in this patient population..

EC决定适用于欧洲经济区（EEA），其中包括欧盟成员国冰岛，列支敦士登和挪威。INAQOVI®是EEA在该患者群体中许可的第一个也是唯一的口服低甲基化剂。。

The EC approval is based on the results from the Phase 3 ASCERTAIN clinical trial investigating the pharmacokinetic exposure equivalence of the novel oral fixed-dose combination versus intravenous (IV) decitabine in AML patients1. The ASCERTAIN study met its primary endpoint, with the orally administered decitabine and cedazuridine fixed-dose combination showing pharmacokinetic exposure equivalence to a standard 5-day regimen of IV decitabine using a two-cycle, cross-over study design.

EC批准基于第3阶段INDEMINE临床试验的结果，该试验研究了AML患者中新型口服固定剂量组合与静脉注射（IV）地西他滨的药代动力学暴露等效性1。INDEMINE研究符合其主要终点，口服地西他滨和头孢噻嗪固定剂量组合显示药代动力学暴露相当于使用双周期交叉研究设计的标准5天IV地西他滨方案。

Safety findings for the fixed-dose combination of decitabine and cedazuridine were generally consistent with those anticipated for IV decitabine1..

地西他滨和头孢唑啶固定剂量组合的安全性结果与IV地西他滨1的预期结果基本一致。。

The current treatment options for adults with AML range from hospital-administered IV chemotherapy infusions or, for those patients not eligible for chemotherapy, regimens based on parenterally administered hypomethylating agents, with treatment cycles typically extending for 5-7 days2. Fatigue can significantly restrict daily activities and impact a patient’s quality of life3.

AML成人目前的治疗方案包括医院给予IV化疗输注，或者对于那些不符合化疗条件的患者，基于肠胃外给予低甲基化剂的方案，治疗周期通常延长5-7天2。疲劳会严重限制日常活动并影响患者的生活质量3。

INAQOVI® may provide both patients and physicians with an oral treatment option in this patient population..

INAQOVI®可为患者和医生提供口服治疗选择。。

On 10th June 2022, the European Medicines Agency (EMA) agreed to a Paediatric Investigation Plan for the oral decitabine and cedazuridine fixed-dose combination, representing an important milestone for the prospect of furthering clinical studies in children with AML.

2022年6月10日，欧洲药品管理局（EMA）同意口服地西他滨和头孢噻吩固定剂量组合的儿科调查计划，这是促进AML儿童临床研究前景的重要里程碑。

About decitabine and cedazuridine fixed-dose combination (INAQOVI®)

关于地西他滨和cedazuridine固定剂量组合（INAQOVI®）

INAQOVI® is an orally administered, fixed-dose combination of the approved hypomethylating agent (HMA), decitabine (35 mg), together with cedazuridine (100 mg), an inhibitor of cytidine deaminase4-6. By inhibiting cytidine deaminase in the gut and liver, the fixed-dose combination is designed to allow for oral daily administration of decitabine over 5 days in a given cycle to achieve comparable systemic exposure to IV decitabine administered with the same dosing regimen7..

INAQOVI®是经批准的低甲基化剂（HMA），地西他滨（35 mg）和胞苷脱氨酶抑制剂cedazuridine（100 mg）4-6的口服固定剂量组合。通过抑制肠道和肝脏中的胞苷脱氨酶，固定剂量组合被设计为允许在给定的周期中在5天内口服地西他滨以实现与用相同给药方案给药的IV地西他滨相当的全身暴露7。。

In the Phase 3 ASCERTAIN study, a total of 89 AML patients were randomised 1:1 to receive INAQOVI® (35 mg decitabine and 100 mg cedazuridine) orally in Cycle 1 and decitabine (20 mg/m2) intravenously in Cycle 2 (n=44) or the reverse sequence (n=45). Both INAQOVI® and IV decitabine were administered once daily on Days 1 through 5 of the 28-day cycle.

在3期DEFINE研究中，共有89名AML患者以1:1的比例随机接受第1周期口服INAQOVI®（35 mg地西他滨和100 mg cedazuridine），第2周期静脉注射地西他滨（20 mg/m2）（n=44）或相反的顺序（n=45）。INAQOVI®和IV地西他滨均在28天周期的第1天至第5天每天给药一次。

Starting with Cycle 3, all patients received INAQOVI® orally once daily on Days 1 through 5 of each 28-day cycle until disease progression, death, or unacceptable toxicity6..

从第3周期开始，所有患者在每个28天周期的第1天至第5天每天口服一次INAQOVI®，直至疾病进展，死亡或不可接受的毒性6。。

Primary endpoint results showed that patients receiving INAQOVI® achieved pharmacokinetic exposure equivalence of 99.64% (90% CI: 91.23, 108.8) to IV decitabine given at 20 mg/m2 for 5-days with a similar pharmacodynamic activity. Secondary findings showed a Median Overall Survival of 7.9 months (95% CI: 5.9, 13.0) and a Complete Response rate of 21.8% at 7.95 months median follow up1..

主要终点结果显示，接受INAQOVI®治疗的患者的药代动力学暴露当量为99.64%（90%CI:91.23108.8），静脉注射地西他滨20 mg/m2，持续5天，具有相似的药效学活性。次要研究结果显示中位随访7.95个月时中位总生存期为7.9个月（95%CI:5.9,13.0），完全缓解率为21.8%。。

The most common adverse drug reaction (≥ 20%) was thrombocytopenia. The most common serious adverse reactions (≥ 20%) were febrile neutropenia and pneumonia. Permanent discontinuation occurred in 14% of patients while on treatment. The most frequent adverse reaction resulting in permanent discontinuation was pneumonia (5%)6..

最常见的药物不良反应（≥20%）是血小板减少症。最常见的严重不良反应（≥20%）是发热性中性粒细胞减少症和肺炎。治疗期间14%的患者永久停药。导致永久停药的最常见不良反应是肺炎（5%）6。。

About acute myeloid leukaemia (AML)

关于急性骨髓性白血病（AML）

AML is the most common form of acute leukaemia in adults8. The median age at diagnosis is approximately 70 years2. Within Europe, the incidence of AML is increasing, this may be attributed to the ageing population; AML incidence in Europe has risen from 3.48 in 1976 to 5.06 patients per 100,000 population in 20132.

AML是成人急性白血病最常见的形式8。诊断的中位年龄约为70岁2。在欧洲，反洗钱的发病率正在上升，这可能归因于人口老龄化；欧洲的AML发病率从1976年的3.48上升到20132年的每10万人5.06例。

Across Europe and all age groups, AML is notably more common in males than in females2. The outlook for patients diagnosed with AML has improved over time due to improved care and treatment, however between the years of 2000 and 2007, 5-year survival for patients was just 17%2..

在欧洲和所有年龄组中，AML在男性中明显多于女性2。由于护理和治疗的改善，诊断为AML的患者的前景随着时间的推移有所改善，但是在2000年至2007年之间，患者的5年生存率仅为17%2。。

About Otsuka

关于大冢

Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy “Otsuka-people creating new products for better health worldwide”. Otsuka researches, develops, manufactures, and markets innovative products, focusing on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

大冢制药是一家全球性的医疗保健公司，其公司理念是“大冢人民创造新产品以促进全球健康”。大冢研究，开发，制造和销售创新产品，专注于满足未满足医疗需求的药品和用于维持日常健康的营养保健品。

In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and has research programmes in several under-addressed diseases including tuberculosis, a significant global public health issue..

在制药领域，大冢是精神卫生领域具有挑战性的领域的领导者，并在包括结核病在内的一些未得到充分解决的疾病方面开展了研究计划，这是一个重要的全球公共卫生问题。。

Otsuka Europe employs around 550 people and focuses on psychiatric and neurologic disorders, infectious disease, nephrology, oncology, and digital medicines. Otsuka Pharmaceutical Europe Ltd. is a part of Otsuka Pharmaceutical Company, Ltd., a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan..

大冢欧洲雇用约550人，专注于精神和神经疾病，传染病，肾脏病，肿瘤学和数字药物。大冢制药欧洲有限公司是大冢制药有限公司的一部分，大冢制药有限公司是大冢控股有限公司的子公司，总部设在日本东京。。

The Otsuka group of companies employed 47,000 people worldwide with consolidated sales of approximately €12.4 billion and a spend of €1.67 billion on research and development in 2022. For further information on Otsuka, please visit www.otsuka-europe.com.

大冢集团在全球雇用了47000人，合并销售额约为124亿欧元，2022年研发支出为16.7亿欧元。有关大冢的更多信息，请访问www.Otsuka-europe.com。

About Astex

关于Astex

Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumours and haematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc.

Astex Pharmaceuticals，Inc。致力于抗癌。Astex正在开发一种专有的新型治疗方法，用于治疗实体瘤和血液系统恶性肿瘤。Astex是大冢集团公司的成员。该集团还包括大冢制药有限公司，太和制药有限公司和太和肿瘤学有限公司。

Subject to regulatory approvals, Astex’s products will be commercialised in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries..

经监管部门批准，Astex的产品将由太和子公司在美国和加拿大商业化，大冢子公司在世界其他地区商业化。。

Otsuka, the Otsuka logo, Astex, the Astex logo, and INAQOVI are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.

大冢，大冢徽标，Astex，Astex徽标和INAQOVI是大冢控股有限公司或其子公司的注册商标。

References

工具书类

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Geissler K，Koristek Z，Bernal del Castillo T等人。口服低甲基化剂ASTX727（DEC-C）与AML中IV地西他滨相比的随机交叉3期研究的药代动力学暴露等效性和初步疗效和安全性耐心。在欧洲血液学协会大会上展示的海报；2022年6月9日至12日；维也纳，奥地利。

Abstract P573..

摘要P573。。

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No authors listed. Benefits of AML Maintenance Therapy Extend to Quality of Life and Hospitalization. Oncologist. 2021;26 (Suppl 1):S11–S12.

没有作者列出。AML维持治疗的益处延伸到生活质量和住院治疗。肿瘤科。2021;26（增补1）：S11–S12。

Oganesian A, Redkar S, Taverna P, et al. Preclinical Data in Cynomolgus Monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel Cytidine Deaminase Inhibitor (CDAi) E7727. Poster presented at the American Society of Hematology Annual Meeting; 7–10 December 2013; New Orleans, LA.

Oganesian A，Redkar S，Taverna P等人。ASTX727食蟹猴的临床前数据，ASTX727是一种新型口服低甲基化剂（HMA），由低剂量口服地西他滨和新型胞苷脱氨酶抑制剂（CDAi）E7727组成。海报在美国血液学会年会上发表；2013年12月7日至10日；新奥尔良，洛杉矶。

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摘要2526。。

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INAQOVI Summary of Product Characteristics (Europe), September 2023.

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