Maternal, Child and Adolescent Health Program, Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia.
Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia.
BMC Pregnancy Childbirth. 2023 Jul 18;23(1):525. doi: 10.1186/s12884-023-05842-9.
There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.
Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.
The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.
This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.
目前用于治疗早产或预防自发性早产的临床药物较少。我们之前制定了预防自发性早产和管理早产的两种目标产品特性（TPP）。本研究的目的是 1）分析预防早产的药物研发管线，2）将这些药物与预防自发性早产的 TPP 进行比较，以确定最有前途的候选药物。
检索 Adis Insight、Pharmaprojects、世界卫生组织国际临床试验注册平台（ICTRP）、PubMed 和资助数据库，以确定候选药物（包括药物、膳食补充剂和生物制剂），并将其纳入加速母亲创新（AIM）数据库。该数据库筛选了所有用于早产研究的候选药物。处于临床开发阶段的候选药物根据 TPP 标准进行排名，并分为高、中、低潜力。临床前候选药物按产品类型、原型和药物亚类进行分类。
AIM 数据库确定了 178 种候选药物。在 71 种处于临床开发阶段的候选药物中，有 10 种被认为具有高潜力（预防：ω-3 脂肪酸、阿司匹林、阴道孕酮、口服孕酮、精氨酸和硒；治疗：尼可地尔、二硝酸异山梨酯、硝苯地平、塞来昔布），7 种具有中潜力（预防：普伐他汀和乳铁蛋白；治疗：甘油三硝酸酯、雷托昔芬、瑞科沙班、人绒毛膜促性腺激素和落地生根提取物）。有 107 种候选药物处于临床前开发阶段。
本分析提供了一种评估预防自发性早产候选药物潜力的无药物方法。应优先研究高潜力候选药物，这些药物最有可能满足妇女、婴儿和医疗保健专业人员的实际需求。
