Expert opinion on investigational drugs最新文献_第5页

Developing targeted therapeutics for hepatocellular carcinoma: a critical assessment of promising phase II agents. 开发肝细胞癌靶向治疗药物：对前景看好的第二阶段药物进行关键评估。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-22 DOI: 10.1080/13543784.2024.2377321

Elisabeth Amadeo, Silvia Foti, Silvia Camera, Federico Rossari, Mara Persano, Federica Lo Prinzi, Francesco Vitiello, Andrea Casadei-Gardini, Margherita Rimini

{"title":"Developing targeted therapeutics for hepatocellular carcinoma: a critical assessment of promising phase II agents.","authors":"Elisabeth Amadeo, Silvia Foti, Silvia Camera, Federico Rossari, Mara Persano, Federica Lo Prinzi, Francesco Vitiello, Andrea Casadei-Gardini, Margherita Rimini","doi":"10.1080/13543784.2024.2377321","DOIUrl":"10.1080/13543784.2024.2377321","url":null,"abstract":"Introduction: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the first for primary liver tumors. In recent years greater therapeutic advancement was represented by employment of tyrosine kinase inhibitors (TKIs) either in monotherapy or in combination with immune checkpoint inhibitors (ICIs).Areas covered: Major attention was given to target therapies in the last couple of years, especially in those currently under phase II trials. Priority was given either to combinations of novel ICI and TKIs or those targeting alternative mutations of major carcinogenic pathways.Expert opinion: As TKIs are playing a more crucial role in HCC therapeutic strategies, it is fundamental to further expand molecular testing and monitoring of acquired resistances. Despite the recent advancement in both laboratory and clinical studies, further research is necessary to face the discrepancy in clinical practice.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"839-849"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Secondary hyperparathyroidism in chronic kidney disease: pathophysiology, current treatments and investigational drugs. 慢性肾病继发性甲状旁腺功能亢进症：病理生理学、当前治疗方法和研究药物。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-06-19 DOI: 10.1080/13543784.2024.2369307

Lorenza Magagnoli, Paola Ciceri, Mario Cozzolino

{"title":"Secondary hyperparathyroidism in chronic kidney disease: pathophysiology, current treatments and investigational drugs.","authors":"Lorenza Magagnoli, Paola Ciceri, Mario Cozzolino","doi":"10.1080/13543784.2024.2369307","DOIUrl":"10.1080/13543784.2024.2369307","url":null,"abstract":"Introduction: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). It begins as an adaptive increase in parathyroid hormone levels to prevent calcium and phosphate derangements. Over time, this condition becomes maladaptive and is associated with increased morbidity and mortality. Current therapies encompass phosphate-lowering strategies, vitamin D analogues, calcimimetics and parathyroidectomy. These approaches harbor inherent limitations, stimulating interest in the development of new drugs for SHPT to overcome these limitations and improve survival and quality of life among CKD patients.Areas covered: This review delves into the main pathophysiological mechanisms involved in SHPT, alongside the treatment options that are currently available and under active investigation. Data presented herein stem from a comprehensive search conducted across PubMed, Web of Science, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) spanning from 2000 onwards.Expert opinion: The advancements in investigational drugs for SHPT hold significant promise for enhancing treatment efficacy while minimizing side effects associated with conventional therapies. Although several challenges still hinder their adoption in clinical practice, ongoing research will likely continue to expand the available therapeutic options, refine treatment strategies, and tailor them to individual patient profiles.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"775-789"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rheumatoid arthritis extra-articular lung disease: new insights on pathogenesis and experimental drugs. 类风湿性关节炎关节外肺病：发病机制和实验药物的新见解。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.1080/13543784.2024.2376567

Marco Sebastiani, Andreina Manfredi, Stefania Croci, Paola Faverio, Giulia Cassone, Caterina Vacchi, Carlo Salvarani, Fabrizio Luppi

{"title":"Rheumatoid arthritis extra-articular lung disease: new insights on pathogenesis and experimental drugs.","authors":"Marco Sebastiani, Andreina Manfredi, Stefania Croci, Paola Faverio, Giulia Cassone, Caterina Vacchi, Carlo Salvarani, Fabrizio Luppi","doi":"10.1080/13543784.2024.2376567","DOIUrl":"10.1080/13543784.2024.2376567","url":null,"abstract":"Introduction: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature.Areas covered: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients.Expert opinion: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"815-827"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature. 治疗类固醇难治性急性移植物抗宿主病的新研究药物：文献综述。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-09 DOI: 10.1080/13543784.2024.2377322

Na Hyun Kim, Mehdi Hamadani, Sameem Abedin

{"title":"New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature.","authors":"Na Hyun Kim, Mehdi Hamadani, Sameem Abedin","doi":"10.1080/13543784.2024.2377322","DOIUrl":"10.1080/13543784.2024.2377322","url":null,"abstract":"Introduction: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments.Areas covered: In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research.Expert opinion: Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"791-799"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety, tolerability and pharmacokinetics of ASC10, a novel oral double prodrug of a broad-spectrum antiviral agent, β-d-N4-hydroxycytidine: results from a randomized, double-blind, placebo-controlled phase 1 study in Chinese healthy subjects. 广谱抗病毒药物β-d-N4-羟基胞嘧啶的新型口服双原药ASC10的安全性、耐受性和药代动力学：针对中国健康受试者的随机、双盲、安慰剂对照1期研究结果。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-12 DOI: 10.1080/13543784.2024.2377318

Jian Liu, Qingwei Zhao, You Zhai, Xia Wu, Jiejing Kai, Jie Ruan, Minglan Wu, Meijia Wu, Zhuojun Zhou, Yuemei Yan, Jinzi J Wu, Yunqing Qiu

{"title":"Safety, tolerability and pharmacokinetics of ASC10, a novel oral double prodrug of a broad-spectrum antiviral agent, β-d-N4-hydroxycytidine: results from a randomized, double-blind, placebo-controlled phase 1 study in Chinese healthy subjects.","authors":"Jian Liu, Qingwei Zhao, You Zhai, Xia Wu, Jiejing Kai, Jie Ruan, Minglan Wu, Meijia Wu, Zhuojun Zhou, Yuemei Yan, Jinzi J Wu, Yunqing Qiu","doi":"10.1080/13543784.2024.2377318","DOIUrl":"10.1080/13543784.2024.2377318","url":null,"abstract":"Background: Considering the rise of new SARS-CoV-2 variants that have reduced the efficacy of COVID-19 vaccines, the development of new antiviral medications for the disease has become increasingly necessary. In this study, ASC10, a novel antiviral prodrug, was studied in a phase 1 trial in healthy Chinese participants.Research design and methods: Part 1 involved 60 participants, receiving 50-800 mg ASC10 or placebo twice daily for 5.5 days. Part 2, with 12 participants, explored ASC10 dosing in the fed/fasting states.Results: ASC10-A, the main pharmacologically active metabolite, rapidly appeared in plasma (Tmax: 1.00-2.00 h) and decreased (t1/2: 1.10-3.04 h) without accumulation. The Cmax and area under the plasma concentration - time curve (AUC) of ASC10-A increased dose-dependently (50-800 mg BID) over 5.5 days, with no accumulation. The Tmax was slightly delayed in the fed state; however, the Cmax and AUC were similar between the fed and fasting states. Adverse events (AEs) were comparable (ASC10/placebo, 66.7%) and mostly mild (95%).Conclusion: ASC10 was demonstrated to be safe and well tolerated and exhibited dose-proportional exposure and minimal food effects.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05523141.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"867-876"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate. 曲妥珠单抗-德鲁司康用于治疗 HER2 改变的实体瘤：从早期研发到抗体药物共轭物首次获得不可知论批准。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-09 DOI: 10.1080/13543784.2024.2376573

Crimini Edoardo, Curigliano Giuseppe

{"title":"Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate.","authors":"Crimini Edoardo, Curigliano Giuseppe","doi":"10.1080/13543784.2024.2376573","DOIUrl":"10.1080/13543784.2024.2376573","url":null,"abstract":"Introduction: Antibody-drug conjugates (ADCs) represent a revolutionary approach in the systemic treatment for both solid and hematologic tumors. Constituted by an antibody, a cytotoxic payload, and a linker, ADCs aim to selectively deliver cytotoxic agents to tumors while sparing normal tissues. Various ADCs have been tested and approved for multiple solid tumors so far, but if there is one that had a major impact on clinical practice, this is Trastuzumab-deruxtecan (T-DXd). Notably, T-DXd was approved for HER2-positive and HER2-low metastatic breast cancer (MBC), HER2-positive gastric cancer (GC), HER2-mutant non-small cell lung cancer (NSCLC) and HER2 3+ solid tumors. Moreover, it received Breakthrough Therapy Designation for HER2-positive colorectal cancer (CRC).Areas covered: We review preclinical and clinical data of T-DXd, focusing on early-phase ongoing trials exploring combination therapies to enhance the activity of T-DXd in HER2-expressing solid tumors.Expert opinion: The clinical use of T-DXd still raises questions about selection of patients, treatment duration, prioritization over other approved ADCs, and management of resistance. Concerns regarding the toxicity of T-DXd remain, particularly with combinations involving potentially toxic drugs. Advancements in biomarker identification and combination therapies offer promising avenues to enhance efficacy and overcome resistance to T-DXd, ultimately improving outcomes for patients with cancer.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"851-865"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigational and emerging gastric inhibitory polypeptide (GIP) receptor-based therapies for the treatment of obesity. 用于治疗肥胖症的基于胃抑制多肽 (GIP) 受体的在研和新兴疗法。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-08-01 Epub Date: 2024-07-17 DOI: 10.1080/13543784.2024.2377319

Robert H Gaffey, Afua K Takyi, Alpana Shukla

{"title":"Investigational and emerging gastric inhibitory polypeptide (GIP) receptor-based therapies for the treatment of obesity.","authors":"Robert H Gaffey, Afua K Takyi, Alpana Shukla","doi":"10.1080/13543784.2024.2377319","DOIUrl":"10.1080/13543784.2024.2377319","url":null,"abstract":"Introduction: One billion people live with obesity. The most promising medications for its treatment are incretin-based therapies, based on enteroendocrine peptides released in response to oral nutrients, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The mechanisms by which GLP-1 receptor agonism cause weight reduction are becoming increasingly understood. However, the mechanisms by which GIP receptor-modulating medications cause weight loss remain to be clarified.Areas covered: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of 'biased agonism' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction.Expert opinion: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"757-773"},"PeriodicalIF":4.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigational bispecific antibodies for the treatment of rheumatoid arthritis. 用于治疗类风湿性关节炎的双特异性抗体研究。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1080/13543784.2024.2351507

Aliki I Venetsanopoulou, Paraskevi V Voulgari, Alexandros A Drosos

{"title":"Investigational bispecific antibodies for the treatment of rheumatoid arthritis.","authors":"Aliki I Venetsanopoulou, Paraskevi V Voulgari, Alexandros A Drosos","doi":"10.1080/13543784.2024.2351507","DOIUrl":"10.1080/13543784.2024.2351507","url":null,"abstract":"Introduction: Rheumatoid arthritis (RA) is an autoimmune disorder with a characteristic chronic inflammation of the synovium that may lead to the destruction of the joints in untreated patients. Interestingly, despite the availability of several effective treatments, many patients do not achieve remission or low disease activity or may experience disease relapse.Following the above unmet needs, bispecific antibodies (BsAbs) have emerged as a new approach to improve the disease's treatment. BsAbs are designed to simultaneously target two different proteins involved in RA pathogenesis, leading to enhanced efficacy and reduced side effects compared to traditional monoclonal antibodies (mAbs).Areas covered: In this review, we discuss the development of BsAbs for RA treatment, including their mechanism of action, efficacy, and safety profile. We also deal with the challenges and future directions in this field.Expert opinion: BsAbs show promise in preclinical and clinical evaluations for treating RA. Further research is needed to optimize design and dosage and identify ideal patient groups. BsAbs can benefit disease management and improve outcomes of RA patients.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"661-670"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lepodisiran, an siRNA targeting lipoprotein(a) for the potential future treatment of cardiovascular disease. Lepodisiran 是一种靶向脂蛋白（a）的 siRNA，未来可能用于治疗心血管疾病。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1080/13543784.2024.2352129

P Mihika S Fernando, Amanda J Hooper, John R Burnett

引用次数: 0

Will new investigational drugs change the way we treat Charcot-Marie-Tooth disease? 新的研究药物是否会改变我们治疗黑热病的方法？

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1080/13543784.2024.2352635

Amedeo De Grado, Chiara Pisciotta, Paola Saveri, Davide Pareyson

引用次数: 0