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抗真菌药物研发进程:隧道尽头有曙光吗?

Antifungal pipeline: Is there light at the end of the tunnel?

作者信息

Schinas Georgios, Spernovasilis Nikolaos, Akinosoglou Karolina

机构信息

Department of Medicine, University of Patras, Patras 26504, Greece.

Department of Infectious Diseases, German Oncology Center, Limassol 4108, Cyprus.

出版信息

World J Clin Cases. 2024 Jun 6;12(16):2686-2691. doi: 10.12998/wjcc.v12.i16.2686.

Abstract

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms, diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets. Despite this pressing need for new treatments, the antifungal drug pipeline has been largely stagnant for the past three decades, primarily due to the high risks and costs associated with antifungal drug development, compounded by uncertain market returns. Extensive research durations, special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to market. In response, the "push-pull" incentive model has emerged as a vital strategy to invigorate the pipeline and encourage innovation. This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents, such as Fosmanogepix, Ibrexafungerp, and Olorofim, while also unraveling the multifaceted challenges faced in new antifungal drug development. The generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance, but it is premature to declare them as definitive solutions. Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges.

摘要

经典抗真菌药物的滥用和过度使用加速了耐药机制的发展,降低了既定治疗途径的疗效,因此有必要转向其他靶点。尽管迫切需要新的治疗方法,但在过去三十年里,抗真菌药物研发渠道基本停滞不前,主要原因是抗真菌药物研发存在高风险和高成本,再加上市场回报不确定。漫长的研究周期、特殊的患者群体以及严格的监管要求,都给新型抗真菌药物推向市场带来了重大障碍。作为回应,“推-拉”激励模式已成为振兴研发渠道和鼓励创新的重要战略。这篇社论批判性地审视了当前的临床形势,并聚焦于新型抗真菌药物,如福沙那韦、依布拉芬净和奥洛罗芬,同时也揭示了新型抗真菌药物研发面临的多方面挑战。新型抗真菌药物的出现为对抗抗菌药物耐药性的斗争带来了一线希望,但宣称它们是终极解决方案还为时过早。它们未来的作用取决于全面的临床验证、成本效益评估以及持续的上市后监测。只有通过战略实施并与市场策略相结合,我们才能改变抗真菌药物研发的局面,应对耐药危机和治疗挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4c8/11185321/0bd208bfafd6/WJCC-12-2686-g001.jpg

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