Drugs最新文献

{"title":"Acoramidis: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40265-025-02159-z","DOIUrl":"https://doi.org/10.1007/s40265-025-02159-z","url":null,"abstract":"<p><p>Disassociation of transthyretin (TTR) has been identified as a key step in the pathology of TTR amyloid cardiomyopathy, which is characterised by the presence of amyloid fibrils in cardiac tissue. Acoramidis (ATTRUBY™) is a small molecule TTR stabiliser being developed by BridgeBio Pharma, Inc. and is the first drug to demonstrate near-complete (> 90%) stabilisation of TTR. This article summarizes the milestones in the development of acoramidis leading to its first approval in the USA for the treatment of the cardiomyopathy of wild-type or variant TTR-mediated amyloidosis in adults to reduce cardiovascular death and cardiovascular-related hospitalization. In the EU, a positive opinion has been adopted for the treatment of wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779430","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 Potential of RNA Therapeutics in Treating Cardiovascular Disease.","authors":"Gayatri Mainkar, Matteo Ghiringhelli, Lior Zangi","doi":"10.1007/s40265-025-02173-1","DOIUrl":"https://doi.org/10.1007/s40265-025-02173-1","url":null,"abstract":"<p><p>Despite significant advances in cardiology over the past few decades, cardiovascular diseases (CVDs) remain the leading cause of global mortality and morbidity. This underscores the need for novel therapeutic interventions that go beyond symptom management to address the underlying causal mechanisms of CVDs. RNA-based therapeutics represent a new class of drugs capable of regulating specific genetic and molecular pathways, positioning them as strong candidates for targeting the root causes of a wide range of diseases. Moreover, owing to the vast diversity in RNA form and function, these molecules can be utilized to induce changes at different levels of gene expression regulation, making them suitable for a broad array of medical applications, even within a single disease context. Several RNA-based therapies are currently being investigated for their potential to address various CVD pathologies. These include treatments aimed at promoting cardiac revascularization and regeneration, preventing cardiomyocyte apoptosis, reducing harmful circulating cholesterols and fats, lowering blood pressure, reversing cardiac fibrosis and remodeling, and correcting the genetic basis of inherited CVDs. In this review, we discuss the current landscape of RNA therapeutics for CVDs, with an emphasis on their classifications, modes of action, advancements in delivery strategies and considerations for their implementation, as well as CVD targets with proven therapeutic potential.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771718","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":"From Prospective Evaluation to Practice: Model-Informed Dose Optimization in Oncology.","authors":"Bram C Agema, Birgit C P Koch, Ron H J Mathijssen, Stijn L W Koolen","doi":"10.1007/s40265-025-02152-6","DOIUrl":"10.1007/s40265-025-02152-6","url":null,"abstract":"<p><p>One dose does not fit all, especially in oncolytic drugs, where side effects and therapy failures highlight the need for personalized dosing approaches. In recent years, the quest to apply model-informed precision dosing to oncology drugs has gained significant momentum, reflecting its potential to revolutionize patient care by tailoring treatments to individual pharmacokinetic profiles. Despite this progress, model-informed precision dosing has not (yet) become widely integrated into routine clinical care. We aimed to explain model-informed precision dosing from a clinical viewpoint while addressing all prospective model-informed precision dosing implementation and validation studies in the field of oncology. We identified 16 different drugs for which prospective model-informed precision dosing validation/implementation has been performed. Although these studies are mostly focused on attaining adequate drug exposures and reducing inter-individual variability, improved clinical outcomes after performing model-informed precision dosing were shown for busulfan, and high-dose methotrexate. Toxicities were significantly reduced for busulfan and cyclophosphamide treatment. In contrast, for carboplatin, for which model-informed precision dosing has been used in the Calvert formula, no prospective validation on outcomes was deemed necessary as the therapeutic window had been extensively validated. Model-informed precision dosing has shown to be of added value in oncology and is expected to significantly change dosing regimens in the future.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"487-503"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406396","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":"Olezarsen: First Approval.","authors":"Yahiya Y Syed","doi":"10.1007/s40265-025-02166-0","DOIUrl":"10.1007/s40265-025-02166-0","url":null,"abstract":"<p><p>Olezarsen (TRYNGOLZA™) is a first-in-class, GalNAc₃-conjugated antisense oligonucleotide being developed by Ionis Pharmaceuticals for the treatment of familial chylomicronaemia syndrome (FCS) and severe hypertriglyceridaemia. It binds to apoC-III mRNA, promoting its degradation and lowering serum apoC-III protein levels. This action lowers triglyceride levels by enhancing the clearance of plasma triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins. GalNAc₃ conjugation improves hepatocyte uptake, which helps localise oligonucleotide treatment to the liver; this enables lower dosing, reduced injection volume and frequency, potentially reducing the risk of adverse events such as thrombocytopenia. Olezarsen received its first approval in the USA on 19 December 2024 under priority review as an adjunct to diet to reduce triglycerides in adults with FCS. This article summarizes the milestones in the development of olezarsen leading to this first approval for FCS.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"571-576"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613988","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":"Safety of Anti-osteoarthritis Medications: A Systematic Literature Review of Post-marketing Surveillance Studies.","authors":"Germain Honvo, Laetitia Lengelé, Majed Alokail, Nasser Al-Daghri, Jean-Yves Reginster, Olivier Bruyère","doi":"10.1007/s40265-025-02162-4","DOIUrl":"10.1007/s40265-025-02162-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Several meta-analyses of phase 3 randomized controlled trials (RCTs) were published in 2019, reassessing the safety of most anti-osteoarthritis (OA) medications, mainly on the basis of data from full safety reports. The current systematic review (SR) intends to provide complementary insights into the safety of anti-OA medications, using evidence from post-marketing safety surveillance studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The review protocol was registered with PROSPERO database (registration no. CRD42021227872). We followed the Cochrane methodology for SRs of interventions and comprehensively searched the Medline, CENTRAL, Scopus and TOXLINE databases from inception to November 2023, to include all post-marketing safety surveillance studies on any anti-OA medications. The outcomes of this SR were any adverse events (AEs) reported in the included studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The literature search yielded 16,990 studies, of which 59 articles were ultimately included in the review. Most studies investigated non-steroidal anti-inflammatory drugs (NSAIDs, 27 studies, 28 reports) and intra-articular hyaluronic acid (IAHA, 16 studies). Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) were assessed in seven studies (one of which also assessed NSAIDs), and corticosteroid injections in four studies, while opioids and \"herbal mixtures and other compounds\" each were investigated respectively in three and two studies. Most of the studies were cohort studies (n = 44), others were case reports or case series (n = 12), RCTs (n = 2 reports of the same trial), or a case-control study (n = 1). The most commonly reported AEs with NSAIDs from cohort (sample sizes varied between 129 and 22,938 patients), RCT (21,645 patients with OA), and case-control (174 cases and 926 control patients with OA) studies were gastrointestinal (GI) and/or cardiovascular (CV) AEs, with specific AEs varying with individual NSAIDs. Where comparisons between NSAIDs were made, the overall literature shows a better or similar safety profile for celecoxib (at a daily dose of 200 mg, where dosage was reported) compared with other NSAIDs in regards to GI, CV and renal events. Other anti-OA medications with most common AEs reported from cohort studies were: IAHA (injection site pain); diacerein (GI AEs and reddish urine); avocado-soybean unsaponifiables (GI AEs); non-pharmaceutical-grade glucosamine and chondroitin (allergic reactions, GI disorders); opioids (hip fracture associated with long-term tramadol use among older adults; GI and nervous system disorders with hydrocodone); corticosteroid injections (increased risk of OA progression); herbal mixtures and other compounds (GI AEs). There were case reports or case series of specific AEs with various anti-OA medications that require further investigations in well-designed cohort studies before any definitive conclusions can be reached.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This SR confirm","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"505-555"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647619","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":"Update on the Treatment of Chronic Spontaneous Urticaria.","authors":"Pavel Kolkhir, Jie Shen Fok, Emek Kocatürk, Philip H Li, Tiia-Linda Okas, Joao Marcelino, Martin Metz","doi":"10.1007/s40265-025-02170-4","DOIUrl":"10.1007/s40265-025-02170-4","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin disease that presents with wheals, angioedema, or both for more than 6 weeks. Less than 10% of patients have complete control of their CSU (the main goal of CSU treatment) with second generation H1-antihistamines, the first-line treatment. About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment. Novel therapies are especially needed for patients with mast cell-activating immunoglobulin (Ig)G autoantibodies (autoimmune CSU) associated with nonresponse or late response to omalizumab. Furthermore, there is a lack of disease-modifying treatments that induce long-term CSU remission after drug withdrawal. Several emerging treatments can address these unmet needs including Bruton tyrosine kinase inhibitors, e.g., remibrutinib and rilzabrutinib; anti-KIT monoclonal antibodies, e.g., barzolvolimab; and anti-cytokine therapies, e.g., dupilumab. In clinical trials, 30-31%, 28-32%, and 38-51% of patients with CSU showed complete response to treatment with dupilumab (phase 3, week 24), remibrutinib (phase 3, week 24), and barzolvolimab (phase 2, week 12), respectively. The most common adverse events were injection site reactions for dupilumab (12%), respiratory tract infections (11%), headache (6%), and petechiae (4%) for remibrutinib and changes in hair color (14%), neutropenia / decreased neutrophil count (9%) and skin hypopigmentation (1%) for barzolvolimab. This review provides an update on the current state of development of treatments for CSU.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"475-486"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613991","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":"Tafolecimab, a Third Monoclonal Antibody for PCSK9 as the Novel Lipid-Lowering Drug Around the World: A Narrative Review.","authors":"Hui-Hui Liu, Sha Li, Jian-Jun Li","doi":"10.1007/s40265-025-02167-z","DOIUrl":"https://doi.org/10.1007/s40265-025-02167-z","url":null,"abstract":"<p><p>Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolemia and has been approved for use in the Chinese population. Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease, and traditional treatments often fall short due to challenges such as statin intolerance. Clinical trials have demonstrated that tafolecimab can effectively reduce LDL-C levels, achieving reductions of over 60% in many patients. It also improves other lipid parameters, including lipoprotein(a) [Lp(a)], non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (ApoB). It has a favorable safety profile, primarily characterized by mild to moderate adverse events. The long-acting formulation of tafolecimab enables less frequent dosing, thereby promoting compliance. As cardiovascular diseases continue to escalate globally, tafolecimab holds promise not only for patients in China but also for broader international applications, representing a critical advancement in the evolving landscape of lipid-lowering therapies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751585","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":"Correction: Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan.","authors":"Carlo Lombardi, Pasquale Comberiati, Erminia Ridolo, Marcello Cottini, Mona Rita Yacoub, Silvia Casagrande, Matteo Riccò, Marco Bottazzoli, Alvise Berti","doi":"10.1007/s40265-025-02149-1","DOIUrl":"10.1007/s40265-025-02149-1","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"599"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476363","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":"Efficiency and Safety of Noninvasive and Intravesical Therapy for Adult Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.","authors":"Qiang Wang, Canyong Li, Yongfu Long, Bin Cao, Yangbo Lu, Gang Luo, Yaqiang Huang, Guiyan Huang, Hongxing Huang","doi":"10.1007/s40265-025-02171-3","DOIUrl":"https://doi.org/10.1007/s40265-025-02171-3","url":null,"abstract":"<p><strong>Background: </strong>Neurogenic lower urinary tract dysfunction (NLUTD), a complex abnormality caused by multiple neurologic disorders, is a serious threat to patients' prognosis and quality of life. However, benefit and safety for various treatments are inconsistent. The aim of the current study was to investigate the available trials of adult NLUTD treatments and provide valuable insights for clinical practice.</p><p><strong>Methods: </strong>The data sources were Medline, Embase, and Cochrane databases up to 31 December 2023. A Bayesian network meta-analysis was conducted with randomized controlled trials in patients who were diagnosed with NLUTD, reporting clinical symptoms and urodynamic data. The main outcomes were incontinence episodes frequency (IEF) and maximum cystometric capacity (MCC). Secondary outcomes included frequency, maximum detrusor pressure, bladder compliance, volume of involuntary detrusor contraction, voided volume, incontinence, quality of life, and adverse events.</p><p><strong>Results: </strong>A total of 54 articles were eligible, evaluating 28 treatments and 4478 patients for efficacy and safety. Compared with the control group, the oxybutynin instillation demonstrated a mean reduction in IEF of - 2.65 episodes (95% confidence interval [CI]: - 4.64 to - 0.67), with a surface under the cumulative ranking curve (SUCRA) value of 85.8%. Botulinum toxin trigone-combined injection resulted in a reduction of -2.30 episodes (95% CI: -3.23 to - 1.44; SUCRA 84.2%). Additionally, intravesical therapies significantly increased MCC: oxybutynin instillation (mean 227.75 mL, 95% CI 147.00 to 311.42, SUCRA 99.1%) and BTX300U (mean 147.88 mL, 95% CI 100.45-190.32, SUCRA 83.2%). Botulinum toxin injection emerged as the preferred option for improving most urodynamic outcomes and quality of life. However, the incidence of adverse events associated with intravesical injections was higher compared with oral medications and other noninvasive therapies. The three types of botulinum toxins (onabotulinum toxin, abobotulinum toxin, and incobotulinum toxin) demonstrated consistent efficacy in treating both IEF and MCC. Individual studies were sequentially excluded for analysis of network stability. Most results from the alternative networks were consistent with the original analysis, although specific trials influenced certain therapy rankings.</p><p><strong>Conclusions: </strong>Overall, oxybutynin instillation and intravesical botulinum toxin injection demonstrated significant advantages in improving symptoms and urodynamic parameters. Our findings support intravesical treatment as a safe and effective option, provided that patients are fully informed about their treatment choices. Clinically, intravesical therapies, oral medications, nerve stimulation, and other treatments should be integrated into shared decision-making processes, while some options require further research to bolster the supporting evidence.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751568","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 Tailored Biosimilar Approach: Expectations and Requirements.","authors":"Elena Guillen, Sean Barry, Nils Jost, Niklas Ekman, Verena Knippel, Johanna Kuhlmann-Gottke, Julia Maier, Martina Weise, Andrea Laslop, René Anour, Ger van Zandbergen, Nadine Kirsch-Stefan","doi":"10.1007/s40265-025-02168-y","DOIUrl":"https://doi.org/10.1007/s40265-025-02168-y","url":null,"abstract":"<p><p>Regulatory approval of biosimilar medicines currently requires a combination of physicochemical and functional testing, pharmacokinetic data, and clinical efficacy studies (CES). In this article, we discuss the tailored biosimilar approach, which represents an evolution in regulatory thinking by moving away from the default requirement for CES in biosimilar approval. We explore how physicochemical and functional data can be predictive for clinical performance and address the limitations of CES for regulatory decision-making. We argue that, in most cases, the combination of a robust package of physicochemical and functional testing, with appropriately designed pharmacokinetic studies provides sufficient evidence to establish biosimilarity. Additionally, we provide our perspective on the requirements, expectations, and exceptions for future biosimilar approvals, outlining specific scenarios where additional clinical evidence may be necessary. These include cases where the mechanism of action is unknown or poorly characterized, when product heterogeneity cannot be adequately characterized, or where relevant safety or immunogenicity concerns arise with the reference product or biosimilar candidate. Finally, we aim to clarify the remaining concerns surrounding the tailored biosimilar approach, providing insights into the potential to streamline biosimilar development and regulatory approval.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763398","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}