Drugs最新文献

{"title":"The Role of CPX-351 in the Acute Myeloid Leukemia Treatment Landscape: Mechanism of Action, Efficacy, and Safety.","authors":"Livio Pagano, Romano Danesi, Edoardo Benedetti, Riccardo Morgagni, Luigina Romani, Adriano Venditti","doi":"10.1007/s40265-025-02194-w","DOIUrl":"10.1007/s40265-025-02194-w","url":null,"abstract":"<p><p>CPX-351 (also known as VYXEOS^® or Vyxeos liposomal) is a dual-drug liposomal encapsulation of cytarabine and daunorubicin in a synergistic 5:1 molar ratio and was the first example that utilized CombiPlex^®, a combination drug technology platform. Superior efficacy with CPX-351 in the pivotal phase 3 randomized clinical trial versus its conventional free-drug counterpart led to its approval for the treatment of newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in multiple countries. Emerging evidence indicates that CPX-351 affords additional benefits compared with conventional chemotherapy, including protection against intestinal dysbiosis and fungal colonization, fewer infectious complications, and a lower incidence of cardiotoxicity. This review examines the mechanisms underlying CPX-351's therapeutic effects and highlights its expanding role in AML treatment by summarizing efficacy and safety data from preclinical models, the pivotal clinical trial, and real-world studies. Particular focus is given to recent findings on CPX-351's intestinal and cardioprotective properties, which together strengthen its safety and efficacy profile compared with conventional chemotherapy.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"855-866"},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973772","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":"Mirdametinib: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40265-025-02190-0","DOIUrl":"10.1007/s40265-025-02190-0","url":null,"abstract":"<p><p>Mirdametinib (GOMEKLI^TM) is an oral small molecule inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) developed by SpringWorks Therapeutics for the treatment of neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas (PN). It is the first therapy to be approved for the treatment of both adults and children with NF1-associated PN in the USA, where it is indicated for use in adult and paediatric patients 2 years of age and older with NF1 who have symptomatic PN not amenable to complete resection. A marketing authorisation application for mirdametinib in NF1-PN is currently under review in the EU. Clinical studies of mirdametinib for the treatment of paediatric low-grade glioma are ongoing. This article summarizes the milestones in the development of mirdametinib leading to this first approval.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"977-984"},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149786","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":"Fitusiran: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40265-025-02203-y","DOIUrl":"https://doi.org/10.1007/s40265-025-02203-y","url":null,"abstract":"<p><p>Haemophilia A and B are inherited bleeding disorders caused by mutations in clotting factors. Small interfering RNA therapies may be utilised to restore coagulation by preventing the synthesis of antithrombin. Fitusiran (QFITLIA™) is a small interfering RNA therapy that targets antithrombin, which is being developed by Sanofi for the prophylactic management of haemophilia A and B with or without inhibitors. Fitusiran has the potential to be administered less frequently than other prophylactic treatments for haemophilia. This article summarizes the milestones in the development of fitusiran leading to this first approval for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and paediatric patients aged 12 years and older with haemophilia A or B with or without factor VIII or IX inhibitors.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511686","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":"https://doi.org/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":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","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}

{"title":"Tiratricol: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-025-02197-7","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","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":"Recaticimab: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-025-02199-5","DOIUrl":"10.1007/s40265-025-02199-5","url":null,"abstract":"<p><p>Recaticimab (^®), a humanized monoclonal immunoglobulin G1 antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), is being developed by Suzhou Suncadia Biopharmaceutical for the treatment of hypercholesteremia and mixed dyslipidemia. Recaticimab received its first approval on 8 January 2025 in China, as an adjunct to diet, in combination with statins (with or without other lipid-lowering therapies) in adults with primary hypercholesterolemia (including heterozygous familial and non-familial hypercholesterolemia) and mixed dyslipidemia who have not achieved their low-density lipoprotein cholesterol (LDL-C) target despite receiving moderate or higher doses of statins, and for use as monotherapy in adults with non-familial hypercholesterolemia and mixed dyslipidemia to reduce LDL-C, total cholesterol, and apolipoprotein B levels. This article summarizes the milestones in the development of recaticimab leading to this first approval for hypercholesterolemia and mixed dyslipidemia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368695","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":"Limertinib: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40265-025-02184-y","DOIUrl":"https://doi.org/10.1007/s40265-025-02184-y","url":null,"abstract":"<p><p>Limertinib (Aoyixin) is an orally available, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been developed for the treatment of non-small cell lung cancer (NSCLC). In clinical trials, limertinib demonstrated efficacy in patients who are positive for the T790M gatekeeper mutation. Limertinib received its first approval for the treatment of adults with locally advanced or metastatic NSCLC with disease progression following treatment with an EGFR TKI and are positive for the EGFR T790M mutation in China in January 2025. In April 2025, limertinib was also approved in China for first-line treatment for adult patients with locally advanced or metastatic NSCLC harbouring EGFR exon 19 deletions or exon 21 L858R mutations. This article summarizes the milestones in the development of limertinib leading to this first approval.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474319","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":"Ivarmacitinib Sulfate: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-025-02202-z","DOIUrl":"10.1007/s40265-025-02202-z","url":null,"abstract":"<p><p>Ivarmacitinib sulfate (ivarmacitinib; ^®), a selective Janus kinase 1 (JAK1) inhibitor, is being developed by Jiangsu Hengrui Pharmaceuticals Co, Ltd Co, Ltd for the treatment of immune-mediated inflammatory diseases. In March 2025, ivarmacitinib was approved for use in adult patients with active ankylosing spondylitis (AS) who have responded poorly to or are intolerant to ≥ 1 tumour necrosis factor (TNF) inhibitors in China. In March 2025, ivarmacitinib was also approved in China for use in adult patients with moderate to severe active rheumatoid arthritis (RA) who have responded poorly to or are intolerant to ≥ 1 TNF inhibitors. In April 2025, ivarmacitinib was approved in China for use in adult patients with moderate to severe atopic dermatitis (AD) who have had an inadequate response or intolerance to topical or other systemic treatments. This article summarizes the milestones in the development of ivarmacitinib leading to this first approval for the treatment of adult patients with active AS.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336345","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":"Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis.","authors":"Naya Huang, Yuanwen Xu, Chan Liu, Yuanying Liu, Yanping Fan, Zeyu Li, Dihua Zhang, Haiping Mao, Wei Chen","doi":"10.1007/s40265-025-02198-6","DOIUrl":"10.1007/s40265-025-02198-6","url":null,"abstract":"<p><strong>Background: </strong>Renin-angiotensin-aldosterone system inhibitors (RAASi) and its combination therapy are essential supportive treatments for patients with chronic kidney disease (CKD) and heart failure (HF). Hyperkalemia (HK) is the major safety concern associated with the treatments, which often leads to RAASi dose reduction or discontinuation, thereby compromising cardiovascular protective effects. Although novel potassium binders (NPBs) are recommended by current guidelines for the treatment of HK, systematic evidence is needed to guide their use in RAASi optimization and HK management. A systematic review and meta-analysis was conducted to evaluate the incidence of HK in patients with CKD or HF who received RAASi and the efficacy of NPBs in RAASi optimization.</p><p><strong>Methods: </strong>PubMed, Medline, Embase, and the Cochrane Library were searched from January 1, 2011 to December 31, 2023. Any studies of adult patients with CKD or HF who received RAASi were included in systematic review of HK incidence and risk factors (part 1). Randomized controlled trials (RCTs) of NPBs in patients with CKD or HF were included in meta-analysis on the efficacy of novel potassium binders (NPBs) (part 2). The primary outcome was optimization of RAASi therapy with NPBs. A pooled analysis was conducted in part 1. Network meta-analyses using a random-effects model were performed in part 2.</p><p><strong>Results: </strong>A total of 83 studies (24 with CKD, 54 with HF, and 5 with CKD and HF) were included in part 1 and 8 RCTs (2 with CKD, 4 with HF, and 2 with CKD and HF) were included in part 2. The pooled HK incidence was 10.7% overall at any criteria and in all patients who received RAASi. The highest incidence of HK was observed with the combination of angiotensin converting enzyme inhibitor (ACEi)/angiotensin ii receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitor (ARNi)+ mineralocorticoid receptor antagonists (MRAs) (24.4%), followed by the triple therapy ACEi/ARB/ARNi+ sodium glucose cotransporter-2 inhibitor (SGLT2i)+MRA (10.9%), and ACEi/ARB/ARNi + SGLT2i (2.2%). Novel potassium binders improved RAASi optimization by 38% compared with placebo (risk ratio, 1.38; 95% CI, 1.16-1.65). Additionally, NPBs decreased the incidence of HK by 28% and reduced the level of potassium by 0.71 mEq/L. The CKD population showed a higher optimization rate than the HF population (84% vs 29%).</p><p><strong>Conclusion: </strong>The RAASi treatment was associated with high prevalence of HK, especially in bigeminal and triple therapy. The NPBs were effective in RAASi optimization and HK management, especially among the CKD population.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340020","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":"Sipavibart: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-025-02186-w","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-09","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}