Gepotidacin

According to the report, the race to create antibiotics and antifungals to conquer superbugs is falling perilously short, which the authors say is putting people across the world at risk. However, a shift in research and development (R&D), including investment in access and stewardship planning, can make a significant impact against antimicrobial resistance (AMR). As most large research-based pharmaceutical companies are no longer active in antimicrobial research and development (R&D), there are very few new treatments making it to market, leaving patients vulnerable to the rapid spread of AMR. Despite this reality, a handful of projects in late-stage clinical development could have a significant impact. Difficult-to-treat invasive, rare fungal mold infections The foundation is tracking five drugs which include gepotidacin, a small molecule commercialized by GSK with a leading phase 3 program in urinary tract infections and F2G’s olorofim, a first of the new orotomide class of antifungals in development for the treatment of difficult-to-treat invasive, rare fungal mold infections. Innoviva’s zoliflodacin is another treatment being tracked and is said to be one of the most promising new treatments for gonorrhoeae currently in phase 3 clinical trials. According to a report in Nature Scientific Reports, studies have found very little resistance to the drug currently circulating in strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. Venatorx’s cefepime-taniborbactam is also under the foundation’s radar. The beta-lactam/beta-lactamase inhibitor (BL/BLI) combination antibiotic is being developed for the treatment of complicated urinary tract infections and hospital acquired bacterial pneumonia. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Pfizer's recently approved aztreonam-avibactam (Emblaveo) is the first β-lactam/β-lactamase inhibitor antibiotic combination approved in the European Union for treating serious infections in adult patients caused by multidrug-resistant gram-negative bacteria, including metallo-β-lactamase-producing bacteria. Emblaveo was reviewed under European Medicines Agency accelerated assessment procedure, used when a pharmaceutical product is of major interest for public health and therapeutic innovation. People living on the frontlines of drug resistance Collectively, these projects could save at least 160,000 lives annually by providing much-needed medicines to treat drug-resistant gonorrhoea, urinary tract infections, intra-abdominal infections, respiratory infections, and invasive fungal infections. While these diseases affect a wide range of patients globally, women and children- especially those living in low-and middle-income countries (LMICs)- are disproportionately affected. Jayasree Iyer, CEO, at the Access to Medicine Foundation, said: “We have a small, but effective, arsenal in the race to combat drug-resistant infections. The difference between us winning or losing this race depends on how companies enable access to people living on the frontlines of drug resistance.” The foundation said that findings reveal that companies are employing diverse range of strategies within their access and stewardship plans but structured advance planning has not yet become standard. Encouragingly, it said, four of the five companies in scope, GSK, Pfizer, Innoviva, and Venatorx, are conducting or initiating clinical trials that directly target children, signalling progress in closing the gap between adult and paediatric access. Tackling the sheer scale and pace of drug resistance Commitments for registration were identified in five LMICs: China, India, Mexico, South Africa, and Thailand. However, for 108 of 113 LMICs in scope, where people also face high burdens of the diseases targeted by these projects, it is currently unclear whether any of them will be made available upon initial approval. The report identifies opportunities and recommendations for companies in focus and outlines actionable steps for global stakeholders in antimicrobial R&D to promote widespread adoption of advance access and stewardship planning. Marijn Verhoef, director of operations and research, at the Access to Medicine Foundation, said: “Tackling the sheer scale and pace of drug resistance is a complex global health issue that will require action from pharmaceutical companies across several areas. This includes providing appropriate access and implementing stewardship measures to safeguard the effectiveness of innovative antimicrobials. Failure to do this will limit efforts to tackle drug resistance.” The foundation added that as global health stakeholders prepare for 2024 UN General Assembly's High-level Meeting on AMR, this report comes at a crucial moment, emphasising the urgent gaps that need attention.

辉瑞（Pfizer）今天宣布，欧盟委员会（EC）批准其与艾伯维（AbbVie）联合开发的Emblaveo（aztreonam-avibactam）上市，用于治疗成人复杂性腹腔内感染（cIAI）、医院获得性肺炎（HAP，包括呼吸机相关性肺炎[VAP]），以及复杂性尿路感染（cUTI，包括肾盂肾炎）。该药物还适用于治疗由需氧革兰氏阴性菌引起感染的成人患者，这些患者的治疗选择有限。根据新闻稿，Emblaveo是首个在欧盟获批使用的β-内酰胺/β-内酰胺酶抑制剂组合，用于治疗由多重耐药革兰氏阴性菌引起的严重细菌感染成人患者。 抗菌素耐药性（AMR）是指细菌、病毒、真菌和寄生虫发生变异，产生抵抗抗菌药物的现象，这被认为是全球健康的最大威胁之一。如果抗菌素耐药性继续不受控制地增加，轻微感染便可能会危及生命，许多常规医疗程序（如剖腹产和髋关节置换术）可能会变得风险太大而无法进行。多重耐药革兰氏阴性菌尤其令人担忧，因为它们导致的发病率和死亡率很高。金属-β-内酰胺酶（MBL）是一种由某些细菌产生的酶，可导致抗生素耐药性，而产生MBL的革兰氏阴性菌在全球范围内呈上升趋势。由于革兰氏阴性菌的传播范围不断扩大，开发革兰氏阴性菌感染的新疗法已被世界卫生组织（WHO）列为重点关注领域。 此次Emblaveo的批准主要基于之前报告的3期研究的结果，该研究由REVISIT和ASSEMBLE试验所组成，旨在评估Emblaveo在治疗由革兰氏阴性菌引起的严重细菌感染（包括产生MBL的多重耐药病原体，对抗这些病原体的治疗选择有限或没有治疗选择）方面的疗效、安全性和耐受性。数据支持Emblaveo有效，之前公布数据显示，Emblaveo对cIAI患者的治愈率为76.4%，而使用活性对照药物治疗患者的治愈率为74.0%。对于HAP和VAP，Emblaveo和活性对照药物的治愈率分别为45.9%和41.7%。 安全性方面，Emblaveo耐受性良好，没有新的安全性发现，其安全性与aztreonam单独使用时相似。 Emblaveo是aztreonam和avibactam这两种抗生素的组合。Aztreonam是一种单环内酰胺抗生素，对需氧革兰氏阴性杆菌有特异性活性。Avibactam则是一种非β-内酰胺类β-内酰胺酶抑制剂，可抑制多种β-内酰胺酶。这些酶包括A类、C类和一些D类酶，它们会削弱铜绿假单胞菌和肠杆菌科细菌等多重耐药病原体中β-内酰胺药物的活性。这两种药物的组合可恢复aztreonam对同时产生MBL和其他β-内酰胺酶细菌的活性，并能够治疗多药耐药的革兰氏阴性菌。 Emblaveo由辉瑞与艾伯维联合开发。辉瑞拥有在美国和加拿大以外地区商业化该疗法的全球权利，而艾伯维则拥有Emblaveo在美国和加拿大的权利。 在2022年的药明康德健康产业论坛中，全球抗菌药生态圈中极具影响力的机构和专家针对AMR此一危机进行全面性的探讨，并指出解决AMR问题的机会首先在于建立强大的新型抗菌药物管线。近年来，WHO正在不断更新细菌和真菌病原体列表，以指导药物研发工作，并同时构建AMR的基础设施，包括疾病监测平台，快速诊断方法和诊断平台以对AMR进行全球范围的监测。全球监测使得科学家能够预测和发现突变、变异株和耐药性的形成，这对于未来管线开发尤其重要。第二个被探讨的机会则是需要构建AMR的新型商业模式，也就是激励处于发现阶段的AMR创新项目被推向临床。这些激励措施可能会弥补AMR市场的短板，起到吸引投资回归的作用，为该领域带来新的资金、创新和科学家。此外，亦有专家建议转向预防策略，从根本上减少抗菌药物的使用需求，将耐药感染控制为少数威胁，而不是越来越大。 针对AMR危机，近年来美国FDA也批准了多款相关项目。去年11月，美国FDA批准DefenCath（牛磺罗定和肝素）导管锁定溶液（CLS）上市，专门用于减少患有肾功能衰竭的成人患者通过中心静脉导管（CVC）接受长期血液透析时发生的与导管相关的血流感染（CRBSIs）。新闻稿指出，DefenCath是FDA批准的首款抗菌CLS，在关键性3期临床试验中，可将CRBSIs风险降低高达71%。今年2月，FDA批准Exblifep（头孢吡肟/enmetazobactam）上市，用于治疗18岁以上cUTI患者，包括治疗肾盂肾炎。这个月，美国FDA再次批准由Basilea Pharmaceutica所开发的Zevtera（ceftobiprole medocaril sodium，注射用）用于治疗金黄色葡萄球菌菌血症（SAB）、急性细菌性皮肤和皮肤结构感染（ABSSSI）以及社区获得性细菌性肺炎（CABP）患者。 近年来许多药企也纷纷加入对抗AMR的行列。除了辉瑞与艾伯维，GSK所开发的潜在“first-in-class”口服抗生素gepotidacin在针对青少年和成人非并发性尿生殖道淋病的关键性3期临床试验EAGLE-1也在这个月取得积极结果。Gepotidacin达到92.6%的微生物学治疗成功率，与活性治疗药物相比达到非劣效性标准。新闻稿指出，如果获批，它将成为20多年来非并发性尿路感染领域首款新类型口服抗生素。 参考资料： [1] European Commission Approves Pfizer’s EMBLAVEO® for Patients with Multidrug-Resistant Infections and Limited Treatment Options. Retrieved April 22, 2024 from https://www.businesswire.com/news/home/20240417715308/en [2] Lahiri SD, Johnstone MR, Ross PL, McLaughlin RE, Olivier NB, Alm RA. Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother. 2014 Oct;58(10):5704-13. doi: 10.1128/AAC.03057-14. Epub 2014 Jul 14. PMID: 25022578; PMCID: PMC4187909. [3] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Aztreonam. [Updated 2017 Aug 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548462/ [4] Phase 3 Studies of Pfizer’s Novel Antibiotic Combination Offer New Treatment Hope for Patients with Multidrug-Resistant Infections and Limited Treatment Options. Retrieved April 22, 2024 from https://www.pfizer.com/news/press-release/press-release-detail/phase-3-studies-pfizers-novel-antibiotic-combination-offer 内容来源于网络，如有侵权，请联系删除。