OSAKA, Japan & CHENNAI, India & GENEVA, Switzerland & BOSTON--(BUSINESS WIRE)--A new agreement is poised to accelerate antibiotic access for tens of thousands of patients in regions with the highest rates of antimicrobial resistance (AMR). The Global Antibiotic Research & Development Partnership (GARDP) and India-based Orchid Pharma Ltd (Orchid) have signed a sublicense agreement to manufacture cefiderocol, an antibiotic to treat certain Gram-negative infections.

大阪，日本和钦奈，印度和日内瓦，瑞士和波士顿-（商业电线）-一项新协议有望加速抗菌药物耐药率（AMR）最高地区成千上万患者的抗生素使用。全球抗生素研究与开发合作伙伴关系（GARDP）和印度兰花制药有限公司（Orchid）签署了一份分许可协议，生产用于治疗某些革兰氏阴性菌感染的抗生素cefiderocol。

This agreement is a critical step in an ambitious project by Shionogi & Co. Ltd. (Shionogi), GARDP, and the Clinton Health Access Initiative (CHAI) that aims to provide access to cefiderocol in a number of predominantly low- and middle- income countries, pending local authorization or national regulatory approval..

该协议是Shionogi＆Co。Ltd.（Shionogi），GARDP和克林顿健康访问倡议（CHAI）雄心勃勃的项目中的关键一步，旨在提供许多主要中低收入国家的cefiderocol，等待当地授权或国家监管部门批准。。

Launched in June 2022, the project represents a new model for bridging global gaps in equitable access to important antibiotics. Even though populations in low- and middle-income countries face a high burden of death from drug-resistant bacterial infections, their access to antibiotics with activity against resistant bacteria is usually delayed by more than a decade.

该项目于2022年6月启动，代表了弥合公平获取重要抗生素的全球差距的新模式。尽管低收入和中等收入国家的人口面临着耐药性细菌感染的高死亡负担，但他们获得具有抗药性细菌活性的抗生素的机会通常会延迟十多年。

That situation may worsen given that the number of serious, potentially life-threatening, infections due to carbapenem-resistant bacteria has been growing across multiple regions, including South Asia and Latin America. By addressing barriers that have historically limited the availability of important antibiotics in low- and middle-income countries, this innovative project aims to accelerate appropriate access for an affordable, quality-assured antibiotic to treat drug-resistant Gram-negative infections..

鉴于碳青霉烯类耐药细菌引起的严重，可能危及生命的感染数量在包括南亚和拉丁美洲在内的多个地区不断增加，这种情况可能会恶化。通过解决历史上限制低收入和中等收入国家重要抗生素供应的障碍，该创新项目旨在加速适当获取负担得起，质量保证的抗生素，以治疗耐药性革兰氏阴性菌感染。。

“Access is one of the least talked about issues in the global AMR crisis. This is not just a global market failure but also a public health failure,” said Manica Balasegaram, Executive Director of GARDP. “We can effectively offset the burden of antibiotic resistance by reducing the access gap between high- and lower-income countries so that the right antibiotics are affordable and available for appropriate use.

GARDP执行董事Manica Balasegaram说：“获取是全球AMR危机中讨论最少的问题之一，这不仅是全球市场失败，也是公共卫生失败。”。“我们可以通过减少高收入和低收入国家之间的准入差距来有效抵消抗生素耐药性的负担，从而使正确的抗生素负担得起并可供适当使用。

We are proud to work with Orchid to help make this a reality for cefiderocol, and we hope that this project can help pave the way for access to additional antibiotics in the future.”.

我们很自豪能与兰花一起帮助实现头孢菌素的这一目标，我们希望该项目能够为将来获得额外抗生素铺平道路。”。

The licensing agreement signed between Shionogi and GARDP in June 2022 enables GARDP to make cefiderocol available in 135 countries (~70% of countries worldwide, including those with the highest AMR burden), none of which currently has access. Cefiderocol was approved by the US Food and Drug Administration in 2019 and the European Medicines Agency in 2020, and it is on the World Health Organization (WHO) Model List of Essential Medicines (please refer to the detailed US indications and Selected Important Safety Information for cefiderocol found below)..

Shionogi和GARDP于2022年6月签署的许可协议使GARDP能够在135个国家（约占全球70%的国家，包括AMR负担最高的国家）提供cefiderocol，目前这些国家都无法获得。Cefiderocol于2019年获得美国食品和药物管理局的批准，并于2020年获得欧洲药品管理局的批准，并列入世界卫生组织（WHO）基本药物标准清单（请参阅美国详细适应症和选定的重要安全信息）Cefiderocol见下文）。。

“We are proud to work with Shionogi, GARDP, and CHAI to provide a global solution to access an important antibiotic for areas of need,” said Manish Dhanuka, Managing Director of Orchid Pharma, one of the world’s leading manufacturers of cephalosporin antibiotics. “Our decades-long expertise in cephalosporins will be advantageous in manufacturing affordable and quality-assured cefiderocol.

兰花制药公司总经理Manish Dhanuka说：“我们很自豪地与Shionogi，GARDP和CHAI合作，为需要的地区提供获得重要抗生素的全球解决方案。”世界领先的头孢菌素抗生素制造商之一。“我们几十年来在头孢菌素方面的专业知识将有利于制造价格合理且质量可靠的头孢菌素。

This will address the unmet needs of patients across low- and middle-income countries where antimicrobial resistance is spreading.”.

这将解决抗菌素耐药性正在蔓延的低收入和中等收入国家患者未满足的需求“。

Orchid was selected following a rigorous vetting process led by CHAI with GARDP. The manufacturing sublicense agreement has important access, environmental, and stewardship provisions, including cost-plus pricing, with a commitment to lower the costs based on volumes to help keep the product affordable for patients and health systems in low-resource settings.

兰花是在CHAI和GARDP领导的严格审查过程中选出的。制造子许可协议具有重要的访问，环境和管理规定，包括成本加定价，承诺根据数量降低成本，以帮助在资源匮乏的环境中保持患者和卫生系统负担得起的产品。

The sublicense access plan, constituting a part of the sublicense agreement, also stipulates that Orchid will submit the product to the WHO medicines prequalification (PQ) programme. Products listed with WHO PQ are eligible for a collaborative procedure for accelerated registration that reduces the time for national regulatory approvals to 90 days in participating countries.

构成子许可协议一部分的子许可访问计划还规定，兰花将向WHO药品资格预审（PQ）计划提交产品。与WHO PQ一起列出的产品有资格获得加速注册的协作程序，从而将参与国的国家监管批准时间缩短至90天。

In March 2023, WHO PQ invited manufacturers of cefiderocol to submit expressions of interest, marking the first instance that WHO PQ opened eligibility to products that treat bacterial infections other than tuberculosis..

2023年3月，WHO PQ邀请cefiderocol制造商提交感兴趣的表达，标志着WHO PQ首次开放了治疗结核病以外细菌感染的产品的资格。。

The signing of the manufacturing sublicense agreement builds on the license agreement between Shionogi and GARDP and on the collaboration agreement between Shionogi, GARDP, and CHAI, both of which were signed in June 2022. Based on these agreements, CHAI will facilitate the technology transfer process between Shionogi and Orchid, and Shionogi will convey essential information for the manufacture of cefiderocol to Orchid, thus accelerating Orchid’s ability to manufacture the product and reducing costs that might otherwise be passed on to patients..

制造子许可协议的签署基于Shionogi和GARDP之间的许可协议以及Shionogi，GARDP和CHAI之间的合作协议，两者均于2022年6月签署。根据这些协议，柴将促进Shionogi和兰花之间的技术转让过程，Shionogi将向兰花传达头孢羟孕酮生产的基本信息，从而加速兰花生产产品的能力并降低可能传递给兰花的成本耐心。。

“Our work goes beyond researching and developing innovative new medicines to address significant unmet medical needs. We are also focused on developing sustainable programmes, including the critically important agreements with GARDP and CHAI, that focus on significant public health priorities, including access to and appropriate use of antibiotics,” said Takuko Sawada, Director and Vice Chairperson of the Board, Shionogi & Co.

“我们的工作不仅仅是研究和开发创新药物，以解决重大未满足的医疗需求。我们还致力于制定可持续计划，包括与GARDP和CHAI达成的至关重要的协议，重点关注重大的公共卫生优先事项，包括获得和适当使用抗生素，“Sawada Takuko说，Shionogi＆Co.董事会主任兼副主席。

Ltd. “We welcome Orchid to this programme and are confident that together we will continue to make strides toward increasing access to medications for people living in low- and middle-income countries.”.

“我们欢迎兰花参加这个项目，并相信我们将继续朝着为中低收入国家的人们增加药物获取的方向迈出一步。”。

“CHAI is deeply committed to access to appropriate diagnosis and treatment for bacterial infections in people living in low- and middle-income countries. We are excited to bring the tools of market shaping to AMR and to support our partners in delivering this unique project to improve patients' lives,” said Dr David Ripin, Executive Vice President, Infectious Diseases and Chief Science Officer, CHAI..

“柴深深地致力于为低收入和中等收入国家的人们提供适当的细菌感染诊断和治疗。我们很高兴将市场塑造工具带入AMR，并支持我们的合作伙伴提供这一独特的项目改善患者的生活，”执行副总裁David Ripin博士说，传染病和首席科学官柴。。

In the spirit of transparency and knowledge sharing, and as a baseline for similar agreements in the future, the license agreement and manufacturing sublicense agreement have been published online.

本着透明度和知识共享的精神，并作为未来类似协议的基准，许可协议和制造子许可协议已在线发布。

About GARDP

关于加德普

The Global Antibiotic Research & Development Partnership (GARDP) is a Swiss not-for-profit organization developing new treatments for drug-resistant infections that pose the greatest threat to health. GARDP was created by the World Health Organization and the Drugs for Neglected Diseases initiative (DNDi) in 2016 and legally founded in 2018 to ensure that everyone who needs antibiotics receives effective and affordable treatment.

全球抗生素研究与开发合作伙伴关系（GARDP）是一家瑞士非营利组织，为对抗药性感染构成最大威胁的抗药性感染开发新疗法。GARDP由世界卫生组织和被忽视疾病药物倡议（DNDi）于2016年创建，并于2018年合法成立，以确保需要抗生素的每个人都能得到有效和负担得起的治疗。

GARDP is funded by the governments of Australia, Germany, Japan, Monaco, the Netherlands, the Public Health Agency of Canada, South Africa, Switzerland, the United Kingdom, the Canton of Geneva, as well as the European Union, Wellcome Trust and private foundations. GARDP is registered under the legal name GARDP Foundation.

GARDP由澳大利亚，德国，日本，摩纳哥，荷兰，加拿大公共卫生署，南非，瑞士，英国，日内瓦州以及欧盟，惠康基金会和私人政府资助。基金会。GARDP以GARDP基金会的法定名称注册。

http://www.gardp.org/.

http://www.gardp.org/.

About Orchid

关于兰花

Established in 1992, Orchid Pharma Ltd. (Orchid) is a vertically integrated pharmaceutical company spanning the entire value chain with established credentials in research, manufacturing, and marketing. Orchid is the only Indian pharmaceutical company ever to have invented a New Chemical Entity (NCE, also colloquially called New Drug) which has cleared global clinical phase III trials..

Orchid Pharma Ltd.（Orchid）成立于1992年，是一家纵向一体化的制药公司，跨越整个价值链，在研究，制造和营销方面拥有成熟的证书。兰花是有史以来唯一发明了一种新的化学实体（NCE，俗称新药）的印度制药公司，该实体已经清除了全球临床III期临床试验。。

The molecule has been submitted for New Drug Approval in the US and Europe. Orchid is a pioneer in the production of quality cephalosporins, especially the sterile products, for which it is one out of few USFDA-approved facilities in the world, and the only one from India. Besides this, Orchid’s facilities are approved worldwide, including approvals like EUGMP, PMDA-Japan, and ANVISA-Brazil.

该分子已提交美国和欧洲的新药批准。兰花是优质头孢菌素生产的先驱，特别是无菌产品，它是世界上少数获得USFDA批准的设施之一，也是唯一来自印度的设施。除此之外，Orchid的设施在全球范围内获得批准，包括EUGMP，PMDA Japan和ANVISA Brazil等批准。

www.orchidpharma.com.

www.orchidpharma.com.

About Shionogi

关于Shionogi

Shionogi & Co., Ltd. is a leading global research-driven pharmaceutical company based in Japan dedicated to bringing benefits to patients based on its corporate philosophy of 'supplying the best possible medicine to protect the health and well-being of the patients we serve.' The company has discovered and developed novel medicines for HIV, influenza and antimicrobial resistance and currently markets products in several therapeutic areas including anti-infectives with the first siderophore cephalosporin.

Shionogi＆Co.，Ltd。是一家位于日本的领先全球研究驱动制药公司，致力于根据其“提供尽可能好的药物以保护我们服务的患者的健康和福祉”的公司理念为患者带来益处该公司已发现并开发出用于艾滋病毒，流感和抗菌素耐药性的新药，目前在几个治疗领域销售产品，包括第一种铁载体头孢菌素的抗感染药物。

We are working to solve healthcare social issues by identifying disease areas with great social needs as core areas for research and development, with a focus on infectious diseases. For more information on Shionogi & Co., Ltd., visit https://www.shionogi.com/global/en/..

我们正在努力解决医疗保健社会问题，将具有重大社会需求的疾病领域确定为研究和发展的核心领域，重点是传染病。有关Shionogi＆Co.，Ltd。的更多信息，请访问https://www.shionogi.com/global/en/..

About CHAI

关于柴

The Clinton Health Access Initiative, Inc. (CHAI) is a global health organization committed to saving lives and reducing the burden of disease in low- and middle-income countries, while strengthening the capabilities of governments and the private sector in those countries to create and sustain high-quality health systems that can succeed without our assistance.

克林顿健康准入倡议公司（CHAI）是一个全球卫生组织，致力于拯救低收入和中等收入国家的生命和减轻疾病负担，同时加强这些国家政府和私营部门的能力。创造和维持没有我们援助就可以成功的高质量卫生系统。

For more information, please visit: http://www.clintonhealthaccess.org..

欲了解更多信息，请访问：http://www.clintonhealthaccess.org..

Other collaborators

其他合作者

GSK

GSK

GSK collaborated with Shionogi to develop cefiderocol, and both companies are committed to support access to medicines for patients living in low- and middle-income countries (LMICs). To help make cefiderocol affordable and available to more people through the Shionogi collaboration with GARDP and CHAI, GSK will forego its royalties from sales in LMICs..

葛兰素史克与Shionogi合作开发了cefiderocol，两家公司都致力于支持生活在低收入和中等收入国家（LMICs）的患者获得药物。通过与GARDP和CHAI的Shionogi合作，帮助使cefiderocol负担得起并向更多人提供，葛兰素史克将放弃其在中低收入国家销售的版税。。

Ping An

平安

Ping An Insurance (Group) Company of China, Ltd. is collaborating with Shionogi to develop cefiderocol in Asia through their joint venture companies, and both companies are committed to supporting access to medicines for patients living in low- and middle-income countries (LMICs). To help make cefiderocol affordable and available to more people in Asia, Ping An Insurance (Group) Company of China, Ltd.

中国平安保险（集团）公司正在与Shionogi合作，通过合资公司在亚洲开发头孢菌素，两家公司都致力于支持中低收入国家患者获得药物（LMICs）。为帮助亚洲更多人负担得起并提供头孢菌素，中国平安保险（集团）有限公司。

supports the Shionogi collaboration with GARDP and CHAI..

支持Shionogi与GARDP和CHAI的合作。。

About cefiderocol

关于头孢菌素

Cefiderocol for injection is the first and only siderophore cephalosporin antibiotic for the treatment of serious Gram-negative infections. It has a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore. In addition to entering cells by passive diffusion through porin channels, cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane via the bacterial iron transporters, which function to incorporate this essential nutrient for bacteria.

注射用Cefiderocol是第一种也是唯一一种用于治疗严重革兰氏阴性菌感染的铁载体-头孢菌素抗生素。它具有作为铁载体穿透革兰氏阴性病原体外细胞膜的新机制。除了通过孔蛋白通道被动扩散进入细胞外，头孢菌素还与三价铁结合，并通过细菌铁转运蛋白通过外膜主动转运到细菌细胞中，细菌铁转运蛋白的功能是掺入这种细菌必需的营养素。

These mechanisms allow cefiderocol to achieve high concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells. Cefiderocol has also demonstrated in vitro activity against certain bacteria that contain problematic resistant enzymes such ESBLs, AmpC, and serine- and metallo-carbapenemases.

这些机制允许cefiderocol在周质空间中达到高浓度，在那里它可以结合青霉素结合蛋白并抑制细菌细胞中的细胞壁合成。Cefiderocol还证明了对某些细菌的体外活性，这些细菌含有有问题的抗性酶，如ESBLs，AmpC，以及丝氨酸和金属碳青霉烯酶。

Data from multinational surveillance studies for cefiderocol demonstrated potent in vitro activity against a wide spectrum of Gram-negative pathogens including carbapenem-resistant A. baumannii complex, P. aeruginosa, Enterobacterales, and S. maltophilia. The clinical significance of the in vitro data is unknown.

来自跨国监测研究的头孢菌素数据显示出对广谱革兰氏阴性病原体的有效体外活性，包括碳青霉烯抗性鲍曼不动杆菌复合物，铜绿假单胞菌，肠杆菌和嗜麦芽窄食单胞菌。体外数据的临床意义尚不清楚。

Cefiderocol has no clinically relevant in vitro activity against most Gram-positive bacteria and anaerobic bacteria..

Cefiderocol对大多数革兰氏阳性菌和厌氧菌没有临床相关的体外活性。。

US INDICATIONS

美国的适应症

Fetroja® (cefiderocol) is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex..

Fetroja®（cefiderocol）适用于18岁或以上的患者，用于治疗复杂的尿路感染（cUTIs），包括由以下易感革兰氏阴性微生物引起的肾盂肾炎：大肠杆菌，肺炎克雷伯菌，奇异变形杆菌，铜绿假单胞菌和阴沟肠杆菌复合体。。

Fetroja is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens..

Fetroja适用于18岁或以上的患者，用于治疗由以下易感革兰氏阴性微生物引起的医院获得性细菌性肺炎和呼吸机相关性细菌性肺炎：鲍曼不动杆菌复合体，大肠杆菌，阴沟肠杆菌复合体，肺炎克雷伯菌，铜绿假单胞菌和粘质沙雷氏菌。。

USAGE

用法

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Fetroja and other antibacterial drugs, Fetroja should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

为了减少耐药细菌的发展并保持Fetroja和其他抗菌药物的有效性，Fetroja只能用于治疗或预防被证实或强烈怀疑由易感细菌引起的感染。

SELECTED IMPORTANT SAFETY INFORMATION

选定的重要安全信息

CONTRAINDICATIONS

禁忌症

Fetroja is contraindicated in patients with a known history of severe hypersensitivity to cefiderocol or other beta-lactam antibacterial drugs, or any other component of Fetroja.

Fetroja禁用于已知对头孢菌素或其他β-内酰胺类抗菌药物或Fetroja任何其他成分有严重超敏反应史的患者。

WARNINGS AND PRECAUTIONS

警告和注意事项

Increase in All-Cause Mortality in Patients with Carbapenem-Resistant Gram-Negative Bacterial Infections

碳青霉烯耐药革兰氏阴性菌感染患者全因死亡率增加

An increase in all-cause mortality was observed in patients treated with Fetroja as compared to best available therapy (BAT) in a multinational, randomized, open-label trial in critically ill patients with carbapenem-resistant Gram-negative bacterial infections (NCT02714595). Patients with nosocomial pneumonia, bloodstream infections, sepsis, or cUTI were included in the trial.

在患有碳青霉烯类耐药革兰氏阴性细菌感染的重症患者（NCT02714595）中，与多国，随机，开放标签试验中的最佳可用疗法（BAT）相比，用Fetroja治疗的患者观察到全因死亡率增加。患有医院内肺炎，血流感染，败血症或cUTI的患者被纳入试验。

BAT regimens varied according to local practices and consisted of 1 to 3 antibacterial drugs with activity against Gram-negative bacteria. Most of the BAT regimens contained colistin..

BAT方案根据当地实践而变化，由1至3种具有抗革兰氏阴性菌活性的抗菌药物组成。大多数BAT方案含有粘菌素。。

The increase in all-cause mortality occurred in patients treated for nosocomial pneumonia, bloodstream infections, or sepsis. The 28-Day all-cause mortality was higher in patients treated with Fetroja than in patients treated with BAT [25/101 (24.8%) vs 9/49 (18.4%), treatment difference 6.4%, 95% CI (-8.6, 19.2)].

全因死亡率的增加发生在接受医院内肺炎，血流感染或败血症治疗的患者中。Fetroja治疗组28天全因死亡率高于BAT治疗组[25/101（24.8%）vs 9/49（18.4%），治疗差异6.4%，95%CI（-8.6，19.2）]。

All-cause mortality remained higher in patients treated with Fetroja than in patients treated with BAT through Day 49 [34/101 (33.7%) vs 10/49 (20.4%), treatment difference 13.3%, 95% CI (-2.5, 26.9)]. Generally, deaths were in patients with infections caused by Gram-negative organisms, including non-fermenters such as Acinetobacter baumannii complex, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, and were the result of worsening or complications of infection, or underlying comorbidities.

Fetroja治疗组患者的全因死亡率在第49天仍然高于BAT治疗组[34/101（33.7%）vs 10/49（20.4%），治疗差异13.3%，95%CI（-2.5,26.9）]。一般来说，死亡是由革兰氏阴性菌引起的感染患者，包括非发酵剂，如鲍曼不动杆菌复合物，嗜麦芽窄食单胞菌，和铜绿假单胞菌，是感染恶化或并发症或潜在合并症的结果。

The cause of the increase in mortality has not been established..

死亡率增加的原因尚未确定。。

Closely monitor the clinical response to therapy in patients with cUTI and HABP/VABP.

密切监测cUTI和HABP/VABP患者对治疗的临床反应。

Click here for Full U.S. Prescribing Information for Fetroja® (cefiderocol).

点击此处获取Fetroja®（cefiderocol）的完整美国处方信息。