Drugs最新文献

{"title":"Nipocalimab: First Approval.","authors":"Simon Fung","doi":"10.1007/s40265-025-02211-y","DOIUrl":"10.1007/s40265-025-02211-y","url":null,"abstract":"<p><p>Nipocalimab (nipocalimab-aahu; IMAAVY™) is a fully human monoclonal antibody that binds to and blocks the neonatal fragment crystallizable (Fc) receptor (FcRn) resulting in the reduction of circulating IgG levels. It is being developed by Johnson & Johnson for the treatment of a number of autoimmune disorders. On 29 April 2025, nipocalimab received its first approval in the USA for the treatment of generalized myasthenia gravis in adult and pediatric patients ≥ 12 years of age who are anti-acetylcholine receptor or anti-muscle specific tyrosine kinase antibody positive. Regulatory review of nipocalimab is underway for generalized myasthenia gravis in Japan and the European Union. This article summarizes the milestones in the development of nipocalimab leading to this first approval for generalized myasthenia gravis.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1185-1192"},"PeriodicalIF":14.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798487","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":"Aldosterone Synthase Inhibitors for Resistant Hypertension: Pharmacological Insights - A Systematic Review.","authors":"Arrigo F G Cicero, Giuliano Tocci, Ashot Avagimyan, Peter Penson, Giulia Nardoianni, Francesco Perone, Claudio Borghi, Federica Fogacci","doi":"10.1007/s40265-025-02229-2","DOIUrl":"10.1007/s40265-025-02229-2","url":null,"abstract":"<p><strong>Background: </strong>Resistant hypertension (RHT) is a challenging clinical condition characterized by persistently elevated blood pressure despite adherence to lifestyle modifications and the use of at least three antihypertensive agents, including a high-dose diuretic. RHT is a heterogeneous condition, influenced by multiple pathophysiological mechanisms such as sodium retention, sympathetic overactivity, and vascular dysfunction. Among these, hyperaldosteronism plays a pivotal role in a subset of patients.</p><p><strong>Methods: </strong>This systematic review examines in depth the pharmacokinetic properties of aldosterone synthase inhibitors (ASIs), with a focus on their therapeutic potential in patients with RHT. A comprehensive literature search was conducted to identify clinical trials and pharmacological studies investigating ASIs, including baxdrostat, dexfadrostat, lorundrostat, LY3045697, and osilodrostat (LCI699).</p><p><strong>Results: </strong>ASIs have shown compelling efficacy in lowering both office-based and 24-h ambulatory blood pressure, particularly in patients with elevated aldosterone levels. These findings underscore the critical role of aldosterone-mediated mechanisms in the pathophysiology of RHT. The inhibitors differ substantially in their metabolic pathways, selectivity profiles, and pharmacokinetic characteristics.</p><p><strong>Conclusions: </strong>Emerging data support the potential of ASIs as a therapeutic option for RHT, particularly when treatment is individualized based on renal function, dietary sodium intake, and comorbidities. Personalized treatment strategies may enhance efficacy, improve tolerability, and support durable blood pressure control in this difficult-to-treat population.</p><p><strong>Registration: </strong>PROSPERO identifier number CRD42024522918 [Graphical abstract available].</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946794","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":"Systemic Therapy for Advanced Thyroid Cancer-New Personalized Options.","authors":"Leslie Cheng, Kate Newbold","doi":"10.1007/s40265-025-02233-6","DOIUrl":"https://doi.org/10.1007/s40265-025-02233-6","url":null,"abstract":"<p><p>Tyrosine kinase inhibitors (TKIs) have revolutionised systemic therapy for advanced thyroid cancers, including radioiodine-refractory differentiated thyroid cancer (RR-DTC), anaplastic thyroid cancer (ATC) and medullary thyroid cancer (MTC), which respond poorly to conventional cytotoxic chemotherapy. The treatment of advanced thyroid cancer is also increasingly personalised, with recent advances in genomic-driven, highly selective targeted therapies. This review summarises contemporary evidence regarding the efficacy, safety and clinical application of drug therapies in thyroid cancers, whilst exploring their evolving role in the age of personalised medicine. Multikinase inhibitors (MKIs) such as sorafenib, lenvatinib, vandetanib and cabozantinib have demonstrated significant improvements in progression-free survival and objective response rates in patients with RR-DTC and MTC. In ATC-a highly lethal tumour-BRAF-directed therapies have shown promising efficacy in patients harbouring the BRAF V600E mutation, yielding enhanced survival outcomes. Moreover, highly-selective inhibitors targeting RET, NTRK and other actionable alterations have refined treatment paradigms by increased integration of molecular testing via next-generation sequencing, ensuring treatments are tailored to the genetic profile of an individual tumour. Despite significant progress, management of advanced thyroid cancer remains challenged by drug resistance and toxicity, underscoring the need for ongoing research and innovation. Furthermore, vast improvements are still required to ensure universal access to molecular testing and targeted therapies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946829","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":"Gepotidacin: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-025-02214-9","DOIUrl":"https://doi.org/10.1007/s40265-025-02214-9","url":null,"abstract":"<p><p>Gepotidacin (BLUJEPA), a small molecule triazaacenaphthylene bacterial type II topoisomerase inhibitor (BTI) antibacterial, has been developed by GSK for the treatment of uncomplicated urinary tract infections (uUTIs) and uncomplicated urogenital gonorrhoea (uUGC). In March 2025, gepotidacin was approved for the treatment of uUTIs caused by susceptible isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis in female adult and paediatric patients aged ≥ 12 years and weighing ≥ 40 kg in the USA. This article summarizes the milestones in the development of gepotidacin leading to this first approval for the treatment of bacterial uUTIs.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783823","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":"QT Prolongation and Risk of Death with the Use of Methadone for Chronic Cancer and Noncancer Pain: Myths or Reality?","authors":"Sebastiano Mercadante","doi":"10.1007/s40265-025-02189-7","DOIUrl":"10.1007/s40265-025-02189-7","url":null,"abstract":"<p><p>The use of methadone has been associated with corrected QT (QTc) prolongation. However, conclusions about the dangers of methadone are limited by its dual use for narcotic abuse deterrence. All these observations can deter physicians from prescribing methadone in patients with chronic pain, particularly those with cancer pain. The aim of this review was to evaluate the existing data regarding the relevance of QT changes, the risk factors for QTc prolongation, as well as the risk for cardiac events and mortality, in patients receiving methadone for chronic pain. In total, 15 studies were evaluated. They differed greatly in design (prospective, retrospective), levels of QTc ranges, number of patients included, and methadone doses. Data suggest that the relevance of QTc prolongation induced by methadone seems to be minimal, also considering the range of dosages commonly used in both noncancer and cancer pain. Some risk factors for QTc prolongation have been identified. Information regarding a prior history or prolonged QTc interval, a family history of a prolonged QTc interval, or a family history of sudden, unexplained death is crucial. In this population and at clinical methadone dosages, serious cardiac events have not been described. Low doses of methadone commonly used in most chronic patients may not require QTc monitoring. When a patient is receiving various medications that could potentially prolong QTc, clinicians may consider obtaining a manually measured QTc. Early discussions with patients regarding goals of care, risks, and benefits will help avoid QTc measurements at regular intervals.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1003-1012"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186766","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: Mirdametinib: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40265-025-02209-6","DOIUrl":"10.1007/s40265-025-02209-6","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1079"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575067","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":"Sipavibart: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-025-02186-w","DOIUrl":"10.1007/s40265-025-02186-w","url":null,"abstract":"<p><p>Sipavibart (KAVIGALE^®), a recombinant human immunoglobulin (Ig)G1-based antibody, is being developed by AstraZeneca for the pre-exposure prophylaxis of COVID-19 in immunocompromised individuals. Sipavibart was approved in December 2024 in Japan to prevent the onset of infection caused by SARS-CoV-2 in adults and adolescents aged ≥ 12 years weighing ≥ 40 kg where vaccination against infection caused by SARS-CoV-2 is not recommended or may not achieve a sufficient immune response. Sipavibart was also approved in the EU for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged ≥ 12 years weighing ≥ 40 kg who are immunocompromised due to a medical condition or receipt of immunosuppressive treatments in January 2025 and in Canada in March 2025. This article summarizes the milestones in the development of sipavibart leading to this first approval for the pre-exposure prophylaxis of COVID-19 in immunocompromised adults and adolescents.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1049-1054"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246992","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":"Rebound Pain After Peripheral Nerve Block: A Review.","authors":"Wenqin Yin, Dan Luo, Haiqi Mi, Zhimin Ren, Lianling Li, Zhidong Fan, Jingyan Lin","doi":"10.1007/s40265-025-02196-8","DOIUrl":"10.1007/s40265-025-02196-8","url":null,"abstract":"<p><p>Peripheral nerve block (PNB) is now a commonly used analgesic treatment in clinical anesthesia owing to ongoing advancements in ultrasound imaging technology, which provides clear images of the nerves. Multimodal analgesia based on peripheral nerve blocks is replacing the conventional opioid-based analgesic strategy. However, after the nerve block effect is removed, some patients experience rebound pain (RP), which exacerbates suffering. The benefits of PNB as a perioperative analgesic may be completely negated if RP is discovered and treated too late, even if it can be promptly managed with analgesics. The definitions, clinical signs, risk factors, pathophysiology, and prevention of RP after PNBs are reviewed in this article. At present, the mechanism of RP after PNB is still unclear, but different types of RP may share similar mechanisms in the pain transmission pathway. In this review, we have determined the characteristics of RP and tried to identify the high-risk factors. Among the many means of preventing and reducing the incidence of RP identified, a single block with adjuvant dexamethasone is a reliable regimen, but for the time being, the application of a catheter would be a more reliable method of reducing RP. This review also provides recommendations for the proper use of nerve blocks as supplemental analgesics under clinical anesthesia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"991-1002"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119244","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":"Tiratricol: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-025-02197-7","DOIUrl":"10.1007/s40265-025-02197-7","url":null,"abstract":"<p><p>Tiratricol (Emcitate^®) is an orally bioavailable small molecule being developed by Egetis Therapeutics for the treatment of monocarboxylate transporter 8 (MCT8) deficiency. Tiratricol, an analogue and metabolite of the thyroid hormone triiodothyronine (T3), has thyromimetic effects but differs from T3 in that it can enter cells independent of MCT8. Tiratricol received its first approval on 12 February 2025 in the European Union, for the treatment of peripheral thyrotoxicosis in patients with MCT8 deficiency (Allan-Herndon-Dudley Syndrome), from birth. Tiratricol will be available as 350 µg dispersible tablets. Tiratricol is currently undergoing clinical development for MCT8 deficiency in several other countries including the USA. This article summarizes the milestones in the development of tiratricol leading to this first approval for MCT8 deficiency.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1059-1065"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474320","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 Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Tao Bai, Zhiyue Xu, Yanbo Zhen, Aijun Liao, Bangmao Wang, Rong Zhao, Yin Zhu, Ning Dai, Side Liu, Hong Zhao, Xi Chen, Kunming Huang, Min Xu, Weizhen Zhou, Baohong Xu, Bin Ye, Duowu Zou, Heng Zhang, Ruihua Shi, Juan Zhang, Yaowei Ai, Xiangming Fang, Lin Lin, Xiaolan Zhang, Ling Zhang, Junping Wang, Yueping Jiang, Jun Cui, Mingxin Zhang, Xiangwu Ding, Zhongyin Zhou, Peng Yan, Xiaoqing Li, Bo Jiang, Youli Liu, Yingcai Ma, Shaoqi Yang, Xiaoyan Wang, Yongdong Wu, Jianjun Wu, Huixin Chen, Xiaohua Hou","doi":"10.1007/s40265-025-02205-w","DOIUrl":"10.1007/s40265-025-02205-w","url":null,"abstract":"<p><strong>Background: </strong>Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.</p><p><strong>Objective: </strong>This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.</p><p><strong>Methods: </strong>This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.</p><p><strong>Results: </strong>After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p  <  0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.</p><p><strong>Conclusions: </strong>Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.</p><p><strong>Clinicaltrials: </strong>GOV: NCT0515132.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1033-1048"},"PeriodicalIF":14.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505151","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}