{"title":"Investigational drugs in early phase trials for myelofibrosis.","authors":"Sankalp Arora, Pankit Vachhani, Prithviraj Bose","doi":"10.1080/13543784.2024.2434696","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation. Therefore, there is a strong need for newer therapies to further advance the field and improve the outcomes of MF. In this review, we cover novel therapies for MF currently in early stages of development.</p><p><strong>Areas covered: </strong>We present the latest data from early phase clinical trials in MF using drugs with diverse therapeutic mechanisms, including novel JAK-STAT pathway inhibitors, epigenetic therapies, antifibrotic agents, and immunotherapeutic strategies. Additionally, we cover drugs targeted toward anemia improvement in MF.</p><p><strong>Expert opinion: </strong>Numerous agents representing diverse drug classes are in clinical development for MF. While deeper and durable improvements in splenomegaly, symptoms, and anemia are the main clinical objectives, a number of putative biomarkers are being assessed as measures of potential 'disease modification.' Although JAK inhibitor monotherapy represents the current standard, it is hoped that JAK inhibitor-based rational combinations and driver mutation-specific therapies will soon usher in a new era.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1231-1244"},"PeriodicalIF":4.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2024.2434696","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation. Therefore, there is a strong need for newer therapies to further advance the field and improve the outcomes of MF. In this review, we cover novel therapies for MF currently in early stages of development.
Areas covered: We present the latest data from early phase clinical trials in MF using drugs with diverse therapeutic mechanisms, including novel JAK-STAT pathway inhibitors, epigenetic therapies, antifibrotic agents, and immunotherapeutic strategies. Additionally, we cover drugs targeted toward anemia improvement in MF.
Expert opinion: Numerous agents representing diverse drug classes are in clinical development for MF. While deeper and durable improvements in splenomegaly, symptoms, and anemia are the main clinical objectives, a number of putative biomarkers are being assessed as measures of potential 'disease modification.' Although JAK inhibitor monotherapy represents the current standard, it is hoped that JAK inhibitor-based rational combinations and driver mutation-specific therapies will soon usher in a new era.
简介骨髓纤维化(MF)是一种慢性骨髓增生性肿瘤,以骨髓纤维化、细胞减少和器官肿大为特征。美国 FDA 批准了四种 JAK 抑制剂用于治疗骨髓纤维化。虽然这些药物在不同程度上减轻了症状负担和脾脏大小,但它们不会影响疾病的自然病程,也不会降低白血病转化的风险。因此,我们亟需更新的疗法来进一步推动该领域的发展并改善 MF 的治疗效果。在这篇综述中,我们将介绍目前处于早期开发阶段的MF新型疗法:我们介绍了使用具有不同治疗机制的药物进行 MF 早期临床试验的最新数据,包括新型 JAK-STAT 通路抑制剂、表观遗传疗法、抗纤维化药物和免疫治疗策略。此外,我们还介绍了针对改善 MF 贫血的药物:针对骨髓纤维化的众多药物正处于临床开发阶段。虽然脾肿大、症状和贫血的深入和持久改善是主要的临床目标,但许多假定的生物标志物正被评估为潜在的 "疾病改变 "指标。虽然 JAK 抑制剂单药疗法是目前的标准疗法,但基于 JAK 抑制剂的合理组合疗法和驱动基因突变特异性疗法有望很快开创一个新时代。
期刊介绍:
Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development.
The Editors welcome:
Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies
Drug Evaluations reviewing the clinical and pharmacological data on a particular drug
Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials
The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.