Drugs最新文献

{"title":"Rezafungin: A Review in Invasive Candidiasis.","authors":"Simon Fung, Matt Shirley","doi":"10.1007/s40265-024-02134-0","DOIUrl":"https://doi.org/10.1007/s40265-024-02134-0","url":null,"abstract":"<p><p>Rezafungin (Rezzayo^®) is a next-generation echinocandin antifungal with improved pharmacokinetic properties over first-generation echinocandins that allows for once-weekly rather than once-daily intravenous administration. It has recently been approved for the treatment of adults with invasive candidiasis in the EU and UK, and is approved for adults who have limited or no alternative options for the treatment of candidaemia and invasive candidiasis in the USA. In the pivotal phase 3 ReSTORE trial, rezafungin was non-inferior to caspofungin (a first-line echinocandin antifungal agent) based both on global cure rates at day 14 and all-cause mortality rates at day 30 in adults with candidaemia or invasive candidiasis. Additionally, the once-weekly administration of rezafungin has the potential advantage of front-loading the dose and increasing drug exposure, with some evidence suggesting that rezafungin may achieve earlier infection clearance relative to caspofungin. Rezafungin was generally well tolerated, with the most common treatment-emergent adverse events being hypokalaemia, pyrexia, diarrhoea and anaemia. Therefore, rezafungin is a useful addition to the treatments currently available for invasive candidiasis in adults, with potential benefits associated with less frequent administration compared with first-generation echinocandins.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ebronucimab: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-025-02146-4","DOIUrl":"https://doi.org/10.1007/s40265-025-02146-4","url":null,"abstract":"<p><p>Ebronucimab (^®) is a subcutaneous fully human anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody being developed by Akeso Biopharma for the treatment of dyslipidaemia. In September 2024, ebronucimab was approved in China, in combination with statins or statins and other lipid-lowering therapies, for adult patients with primary hypercholesterolaemia [including heterozygous familial hypercholesterolaemia (HeFH)] and mixed hyperlipidaemia who are unable to achieve the low-density lipoprotein cholesterol target after receiving moderate or higher doses of statins. This article summarizes the milestones in the development of ebronucimab leading to this first approval for primary hypercholesterolaemia, mixed hyperlipidaemia and HeFH.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal Irinotecan: A Review as First-Line Therapy in Metastatic Pancreatic Adenocarcinoma.","authors":"Michael B Brown, Hannah A Blair","doi":"10.1007/s40265-024-02133-1","DOIUrl":"10.1007/s40265-024-02133-1","url":null,"abstract":"<p><p>Liposomal irinotecan (Onivyde^®), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The safety profile of NALIRIFOX was generally manageable, with diarrhoea, hypokalaemia and neutropenia being the most common grade ≥ 3 treatment-emergent adverse events. Although further analyses will help position the liposomal irinotecan-containing regimen NALIRIFOX in first-line treatment of metastatic pancreatic adenocarcinoma, current evidence indicates that it is a useful addition to treatment options in this patient population.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"255-262"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2- Early Breast Cancer.","authors":"Eva Valentina Klocker, Daniel Egle, Rupert Bartsch, Gabriel Rinnerthaler, Michael Gnant","doi":"10.1007/s40265-024-02144-y","DOIUrl":"10.1007/s40265-024-02144-y","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"149-169"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: \"The Utilization of the Accelerated Approval Pathway in Oncology: A Case Study of Pembrolizumab\".","authors":"Raffaele Giusti","doi":"10.1007/s40265-024-02139-9","DOIUrl":"10.1007/s40265-024-02139-9","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"279-280"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aligning Large Language Models with Humans: A Comprehensive Survey of ChatGPT's Aptitude in Pharmacology.","authors":"Yingbo Zhang, Shumin Ren, Jiao Wang, Junyu Lu, Cong Wu, Mengqiao He, Xingyun Liu, Rongrong Wu, Jing Zhao, Chaoying Zhan, Dan Du, Zhajun Zhan, Rajeev K Singla, Bairong Shen","doi":"10.1007/s40265-024-02124-2","DOIUrl":"10.1007/s40265-024-02124-2","url":null,"abstract":"<p><strong>Background: </strong>Due to the lack of a comprehensive pharmacology test set, evaluating the potential and value of large language models (LLMs) in pharmacology is complex and challenging.</p><p><strong>Aims: </strong>This study aims to provide a test set reference for assessing the application potential of both general-purpose and specialized LLMs in pharmacology.</p><p><strong>Methods: </strong>We constructed a pharmacology test set consisting of three tasks: drug information retrieval, lead compound structure optimization, and research trend summarization and analysis. Subsequently, we compared the performance of general-purpose LLMs GPT-3.5 and GPT-4 on this test set.</p><p><strong>Results: </strong>The results indicate that GPT-3.5 and GPT-4 can better understand instructions for information retrieval, scheme optimization, and trend summarization in pharmacology, showing significant potential in basic pharmacology tasks, especially in areas such as drug pharmacological properties, pharmacokinetics, mode of action, and toxicity prediction. These general LLMs also effectively summarize the current challenges and future trends in this field, proving their valuable resource for interdisciplinary pharmacology researchers. However, the limitations of ChatGPT become evident when handling tasks such as drug identification queries, drug interaction information retrieval, and drug structure simulation optimization. It struggles to provide accurate interaction information for individual or specific drugs and cannot optimize specific drugs. This lack of depth in knowledge integration and analysis limits its application in scientific research and clinical exploration.</p><p><strong>Conclusion: </strong>Therefore, exploring retrieval-augmented generation (RAG) or integrating proprietary knowledge bases and knowledge graphs into pharmacology-oriented ChatGPT systems would yield favorable results. This integration will further optimize the potential of LLMs in pharmacology.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"231-254"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Complicated Gram-Positive Bacteremia and Infective Endocarditis.","authors":"Paul Schellong, Oana Joean, Mathias W Pletz, Stefan Hagel, Sebastian Weis","doi":"10.1007/s40265-024-02135-z","DOIUrl":"10.1007/s40265-024-02135-z","url":null,"abstract":"<p><p>The Gram-positive cocci Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. are the most frequent causative organisms of bloodstream infections and infective endocarditis. \"Complicated bacteremia\" is a term used in S. aureus bloodstream infections and originally implied the presence of metastatic infectious foci (i.e. complications of S. aureus bacteremia). These complications demand longer antimicrobial treatment durations and, frequently, interventional source control. Several risk factors for the incidence of bacteremia complications have been identified and are often used for the definition of complicated bacteremia. Here, we discuss management and diagnostic approaches and treatment options for patients with complicated bacteremia, with particular focus on infective endocarditis. We also summarize the available evidence regarding imaging modalities and the choice of antimicrobial mono- or combination therapy according to resistance patterns for these pathogens as well as treatment durations and optimized application routes. Finally, we synopsize current and future areas of research in complicated bacteremia and infective endocarditis.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"193-214"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and Emerging Therapies for Lysosomal Storage Disorders.","authors":"Diego Agustín Abelleyra Lastoria, Sophie Keynes, Derralynn Hughes","doi":"10.1007/s40265-025-02145-5","DOIUrl":"10.1007/s40265-025-02145-5","url":null,"abstract":"<p><p>Lysosomal storage disorders (LSDs) are rare inherited metabolic disorders characterized by defects in the function of specific enzymes responsible for breaking down substrates within cellular organelles (lysosomes) essential for the processing of macromolecules. Undigested substrate accumulates within lysosomes, leading to cellular dysfunction, tissue damage, and clinical manifestations. Clinical features vary depending on the degree and type of enzyme deficiency, the type and extent of substrate accumulated, and the tissues affected. The heterogeneous nature of LSDs results in a variety of treatment approaches, which must be tailored to patient presentation and characteristics. The treatment landscape for LSDs is rapidly evolving. An up-to-date discussion of current evidence is required to provide clinicians with an appropriate overview of treatment options. Therefore, we aimed to review current and ongoing trials pertaining to the treatment of common LSDs.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"171-192"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inavolisib: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-024-02136-y","DOIUrl":"10.1007/s40265-024-02136-y","url":null,"abstract":"<p><p>Inavolisib (Itovebi^™) is an orally administered, phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor being developed by Genentech, a member of the Roche group, for the treatment of solid tumours. On 10 October 2024, inavolisib received its first approval in the USA in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. In the EU and other countries worldwide, regulatory review of inavolisib is currently underway. This article summarises the milestones in the development of inavolisib leading to this first approval for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"271-278"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Microbiome Therapeutics.","authors":"Milena Pitashny, Inbar Kesten, Dima Shlon, Dana Ben Hur, Haggai Bar-Yoseph","doi":"10.1007/s40265-024-02107-3","DOIUrl":"10.1007/s40265-024-02107-3","url":null,"abstract":"<p><p>The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"117-125"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}