Okwu Dearie Glory, Zoleko Manego Rella, Duparc Stephan, Kremsner Peter Gottfried, Ramharter Michael, Mombo-Ngoma Ghyslain
Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon; Department of Implementation Research, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon; German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany; Centre for Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Clin Microbiol Infect. 2025 Jun;31(6):941-947. doi: 10.1016/j.cmi.2025.03.009. Epub 2025 Mar 20.
In 2022, malaria caused approximately 249 million cases and 608,000 deaths, primarily in Africa. Current treatments target asexual blood-stage parasites, gametocytes, and liver hypnozoites. Standard guidelines recommend a 3-day course of artemisinin-based combination therapies as a first-line treatment of uncomplicated malaria and parenteral artesunate for severe malaria. However, the emergence of partial resistance to artemisinin derivatives threatens the treatment efficacy, highlighting the urgent need for novel antimalarial drugs.
This review summarizes recent progress in the clinical development of antimalarials particularly non-artemisinin compounds under target product profile-1.
Data were gathered from Medicines for Malaria Venture (MMV)'s portfolio and clinical trial databases between 2020 and 2024.
Sixteen clinical trials were reviewed, including safety and efficacy studies involving healthy volunteers, experimentally infected volunteers, asymptomatic Plasmodium falciparum carriers and malaria patients. Six trials evaluated the safety and tolerability of MMV533, ZY19489, INE963, GSK701/MMV367 and intravenous KAE609 in healthy volunteers. Efficacy trials involving experimentally infected volunteers assessed ZY19489 and GSK701/MMV367, whereas studies on asymptomatic carriers tested ZY19489/ferroquine and cabamiquine/pyronaridine. Trials on malaria patients investigated combinations of ganaplacide/lumefantrine-SDF, cabamiquine/pyronaridine, both oral and intravenous cipargamin and INE963.
Although attrition remains a possibility, several promising candidate drugs with novel modes of action are advancing through clinical development. Many are expected to become available for treating uncomplicated and severe malaria within the next decade. These new antimalarials could significantly enhance malaria treatment, reduce resistance, and support global health efforts towards malaria control, elimination and, potentially, eradication.
2022年，疟疾导致约2.49亿例病例和60.8万人死亡，主要发生在非洲。目前的治疗方法针对无性血液期寄生虫、配子体和肝脏休眠子。标准指南推荐以青蒿素为基础的联合疗法进行为期3天的疗程作为非复杂性疟疾的一线治疗方法，对于重症疟疾则采用蒿甲醚注射液。然而，对青蒿素衍生物出现的部分耐药性威胁到治疗效果，凸显了对新型抗疟药物的迫切需求。
本综述总结了抗疟药物特别是符合目标产品概况-1的非青蒿素化合物临床开发的最新进展。
数据收集自疟疾药物事业（MMV）2020年至2024年的产品组合和临床试验数据库。
审查了16项临床试验，包括涉及健康志愿者、实验感染志愿者、无症状恶性疟原虫携带者和疟疾患者的安全性和有效性研究。六项试验评估了MMV533、ZY19489、INE963、GSK701/MMV367和静脉注射KAE609在健康志愿者中的安全性和耐受性。涉及实验感染志愿者的疗效试验评估了ZY19489和GSK701/MMV367，而对无症状携带者的研究测试了ZY19489/非诺喹和卡巴喹/咯萘啶。对疟疾患者的试验研究了甘氨酰胺醇/本芴醇-SDF、卡巴喹/咯萘啶、口服和静脉注射西帕加明以及INE963的组合。
尽管仍有可能被淘汰，但几种具有新作用模式的有前景的候选药物正在推进临床开发。预计许多药物将在未来十年内可用于治疗非复杂性和重症疟疾。这些新型抗疟药物可显著增强疟疾治疗效果、降低耐药性，并支持全球疟疾控制、消除乃至可能根除疟疾的卫生工作。
