Zoliflodacin

阿姆斯特丹 2024年5月23日 /美通社/ -- 开发替代抗生素和抗真菌药物来对 抗超级细菌的竞赛严重不足，使世界各地的人们处于危险之中。但是，研发（R&D）的转变，包括对准入和管理规划的投资，可以对抗微生物药物耐药性（AMR）产生重大影响。 由于大多数以研究为基础的大型制药公司不再活跃于抗微生物药物研发，因此上市的新疗法很少，这使得患者容易受到抗微生物药物耐药性快速传播的影响。尽管存在这种现实，但少数处于后期临床开发阶段的项目可能会产生重大影响。 A ccess to Medicine Foundation的新报告 追踪了葛兰素史克、F2G、Innoviva、Venatorx（分别为gepotidacin、olorofim、zoliflodacin和cefepime-taniborbactam）和辉瑞最近批准的阿曲南阿维巴坦（Emblaveo®）管道中的五个此类项目。通过提供急需的药物来治疗耐药性淋病、尿路感染、腹腔内感染、呼吸道感染和侵入性真菌感染，这些项目每年总共可以挽救至少16万人的生命。 尽管这些疾病影响着全球范围广泛的患者，但妇女和儿童，尤其是生活在低收入和中等收入国家（LMIC）的妇女和儿童，受到的影响尤其严重。 "在抗击耐药感染的竞赛中，我们的武器规模虽小但有效。 我们在这场竞赛中获胜与失败的区别取决于公司如何为生活在耐药前线的人们提供机会 。" — 医学准入基金会首席执行官贾亚斯里•艾耶。 调查结果显示，各公司在其准入和管理计划中采用了多种策略，但结构化的预先计划尚未成为标准。令人鼓舞的是，在范围内的五家公司中，有四家——葛兰素史克、辉瑞、Innoviva和Venatorx——正在进行或启动直接针对儿童的临床试验，这表明在缩小成人和儿科准入差距方面取得了进展。五个低收入国家确定了注册承诺：中国、印度、墨西哥、南非和泰国。但是，对于范围内的113个中低收入国家中的108个，人们也面临着这些项目针对的疾病的沉重负担，目前尚不清楚在初步批准后是否会提供这些项目。 该报告为重点公司确定了机遇和建议，并概述了全球利益相关者在抗微生物药物研发领域的可行措施，以促进广泛采用预先准入和管理规划。 "应对耐药性的巨大规模和速度是一个复杂的全球健康问题，需要制药公司在多个领域采取行动。这包括提供适当的准入和实施管理措施，以保障创新抗微生物药物的有效性。不这样做将限制解决耐药性的努力。"——准入医学基金会运营与研究总监 玛丽恩•维尔霍夫。 在全球卫生利益相关者 为2024年联合国大会抗菌素耐药性 高级别会议做准备之际，本报告是在关键时刻发布的，强调了需要注意的紧迫差距。在这里阅读 报告 。

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 As most large research-based pharmaceutical companies are no longer active in antimicrobial research and development (R&D), there are very few new treatments making it to market, leaving patients vulnerable to the rapid spread of AMR.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.