Drugs最新文献

{"title":"Sibeprenlimab: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40265-026-02298-x","DOIUrl":"10.1007/s40265-026-02298-x","url":null,"abstract":"<p><p>Sibeprenlimab (VOYXACT^®; sibeprenlimab-szsi) is a fully humanized monoclonal antibody that binds to A PRoliferation Inducing Ligand (APRIL) being developed by Otsuka Pharmaceutical for the treatment of immunoglobulin A (IgA) nephropathy and Sjögren's disease. Signalling via APRIL is implicated in the inflammatory processes that ultimately result in damage to the glomeruli in patients with IgA nephropathy. Treatment with sibeprenlimab suppressed APRIL levels and reduced proteinuria in patients with IgA nephropathy, according to interim analyses from the ongoing VISIONARY phase III clinical trial. This article summarizes the milestones in the development of sibeprenlimab leading to this first approval to reduce proteinuria in adults with primary IgA nephropathy at risk for disease progression.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"765-768"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493764","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 of Renin Angiotensin Aldosterone System Inhibitors on Cardiovascular Outcomes in Hypertensive Population: A Network Meta-analysis of Randomized Controlled Trials.","authors":"Yueming Jiang, Jinbo Hu, Xiaoyan Yi, Qifu Li, Shumin Yang","doi":"10.1007/s40265-026-02302-4","DOIUrl":"10.1007/s40265-026-02302-4","url":null,"abstract":"<p><strong>Background: </strong>Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear.</p><p><strong>Objectives: </strong>We aimed to compare the efficacy of RAAS inhibitors on cardiovascular outcomes in hypertensive population.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed and the Central Cochrane Library. The primary efficacy outcome was major adverse cardiovascular events (MACE). Individual components of MACE including cardiovascular mortality, myocardial infarction, stroke, and heart failure were also analyzed. Network meta-analyses were conducted via a random-effects model within frequentist framework.</p><p><strong>Results: </strong>We analyzed 43 randomized controlled trials. Mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of MACE compared with placebo [risk ratio (RR) 0.82; 95% confidence interval (CI) 0.75-0.90] and were superior to angiotensin receptor blockers (ARBs; RR 0.87; 95% CI 0.78-0.99) and direct renin inhibitors (DRIs; RR 0.83; 95% CI 0.70-0.99). MRAs showed a nonsignificant trend toward benefit compared with angiotensin-converting enzyme inhibitors (ACEIs; RR 0.91; 95% CI 0.78-1.05). After excluding trials that specifically enrolled patients with heart failure, protective effect of MRAs was not significant, but suggested a trend toward benefit (RR 0.89; 95% CI 0.78-1.01). Subgroup analyses for diabetes and chronic kidney disease consistently showed significant MACE reduction with MRAs, regardless of whether patients had these comorbidities at baseline or not, while other RAAS inhibitors showed inconsistent results in the subgroup analysis. For individual events, MRAs showed higher efficacy in reducing cardiovascular mortality (RR 0.80; 95% CI 0.72-0.88) and heart failure (RR 0.83; 95% CI 0.70-0.98) compared with placebo, while ACEIs were more effective in reducing myocardial infarction (RR 0.65; 95% CI 0.51-0.82) and ARBs showed higher efficacy in reducing stroke (RR 0.88; 95% CI 0.80-0.98) compared with placebo.</p><p><strong>Conclusions: </strong>MRAs outperformed ARBs and DRIs in reducing MACE in patients with hypertension, with a nonsignificant trend toward benefit compared with ACEIs. This benefit was most pronounced in populations with heart failure and MRAs provided consistent cardiovascular protection across subgroups with diabetes or renal comorbidities. Given the current positioning of the guidelines, MRAs may merit earlier consideration in hypertension management, pending confirmatory outcome-driven randomized trials.</p><p><strong>Registration: </strong>PROSPERO identifier number CRD42023473004, registered on 28 October 2023.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"737-752"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473018","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":"GOLD 2026: Transforming COPD Management with Early Intervention, Multi-dimensional Assessment, and Personalized Care.","authors":"Mario Cazzola, Jyoti Bajpai, Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani","doi":"10.1007/s40265-026-02303-3","DOIUrl":"10.1007/s40265-026-02303-3","url":null,"abstract":"<p><p>The 2026 report from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduces substantial conceptual and practical updates to the management of chronic obstructive pulmonary disease. While maintaining the established spirometric definition, the report emphasizes early diagnosis, multi-dimensional assessment, and personalized treatment strategies that move beyond a spirometry-centric approach. Key innovations include formally recognizing disease activity as a therapeutic target, refining the ABE classification with a lower threshold for patients prone to exacerbations (Group E), and integrating blood eosinophil counts to guide inhaled corticosteroid therapy. Nonpharmacologic interventions, such as pulmonary rehabilitation, vaccination, smoking cessation, structured self-management, and post-exacerbation care, are elevated to core disease-modifying strategies. Pharmacological escalation is structured around dual bronchodilation as the preferred initial step, with further intensification to biomarker-guided triple therapy, including inhaled corticosteroids or other anti-inflammatory agents, reserved for selected patients who remain symptomatic or experience exacerbations despite optimized dual therapy. GOLD 2026 also introduces biologics, dupilumab and mepolizumab, as an add-on therapy for exacerbation-prone eosinophilic chronic obstructive pulmonary disease. However, it also highlights ongoing limitations in efficacy, cost effectiveness, and generalizability. Artificial intelligence and emerging digital technologies are recognized as promising adjuncts in the management of chronic obstructive pulmonary disease, though their clinical implementation remains preliminary. Overall, GOLD 2026 advances precision medicine in chronic obstructive pulmonary disease by combining structured individualized assessments with early targeted interventions. However, significant uncertainties remain, including biological variability of biomarkers, limited evidence for emerging therapies, and barriers to equitable access to nonpharmacologic and advanced interventions. Careful context-sensitive application and continued validation are essential.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"581-597"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431517","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":"Pharmacological, Natural and Emerging Therapies for Meibomian Gland Dysfunction: A Review.","authors":"Jordan M Cooper, Ryan Mahmoud, Catherine J Jennings, Kalika Bandamwar, Michael T M Wang, Jennifer P Craig","doi":"10.1007/s40265-025-02241-6","DOIUrl":"10.1007/s40265-025-02241-6","url":null,"abstract":"<p><p>Meibomian gland dysfunction (MGD) is a leading cause of non-aqueous deficient dry eye disease. Meibomian glands are responsible for the production of meibum, a lipid-rich secretion that coats the surface of the tear film, inhibiting evaporation of the underlying aqueous tear fluid. MGD can arise due to numerous extrinsic and intrinsic factors that drive changes in meibum quality or obstruction of gland orifices and can result in tear film instability, hyperosmolarity, epithelial damage and downstream ocular surface inflammation. Despite the high disease prevalence, management is not standardised, with a wide range of pharmacological and naturally derived therapies available. Potential pharmacological agents include anti-inflammatories (antibiotics, immunosuppressants and topical integrin antagonists), perfluorohexyloctane and topical aqueous secretagogues. Natural therapies that may offer suitable long-term solutions include oral dietary supplements (polyunsaturated fatty acids, astaxanthin, bilberry, Chinese herbal formulations and Korean red ginseng) and naturally derived topical formulations (castor oil, manuka honey, tea tree oil, coenzyme Q10 and green tea extract). The rising prevalence of MGD has led to the development of several novel therapeutic strategies, expanding the range of management options available to clinicians. A thorough examination should precede the initiation of treatment to identify underlying pathophysiology and guide targeted interventions. Treatment efficacy, duration and safety profiles must also be considered.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"675-718"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608245","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":"Retlirafusp Alfa: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-026-02305-1","DOIUrl":"10.1007/s40265-026-02305-1","url":null,"abstract":"<p><p>Retlirafusp alfa (^®), a bifunctional antibody fusion protein combining a PD-L1-targeting antibody with a truncated form of the TGF-β receptor II (TGF-βRII) extracellular domain, is being developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd for the treatment of solid malignant tumours. In January 2026, retlirafusp alfa was approved for use in combination with fluorouracil and platinum-based drugs as a first-line treatment for locally advanced, unresectable, recurrent, or metastatic gastric cancer and gastroesophageal junction adenocarcinoma (GC/GEJA) with a PD-L1 positive CPS ≥ 1, as assessed by a well-validated assay in China. This article summarizes the milestones in the development of retlirafusp alfa leading to this first approval for the treatment of advanced PD-L1 positive GC/GEJA.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"769-775"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490808","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: Avutometinib and Defactinib: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-026-02296-z","DOIUrl":"10.1007/s40265-026-02296-z","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"777"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638373","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":"Polidocanol in Sclerotherapy for Lymphovenous Disorders: Mechanisms, Clinical Uses, and Future Prospects.","authors":"K S Soya Parveen, K Sreekanth, N Radhakrishnan, K Jayachandran, E K Radhakrishnan","doi":"10.1007/s40265-026-02300-6","DOIUrl":"10.1007/s40265-026-02300-6","url":null,"abstract":"<p><p>Polidocanol is a widely recognised drug for its effectiveness as a sclerosant in the treatment of lymphovenous disease. The versatility and minimal invasiveness of polidocanol make it a favoured treatment modality for chronic venous disease (CVD) and other venous and vascular disorders. Especially, polidocanol foam sclerotherapy achieves high closure rates and efficiency compared to thermal ablation, in cases of venous hypertension affecting small tributary veins of the peripheral venous system. The underlying pathophysiology of these venous disorders is multifactorial. Elevated venous hypertension and related microcirculatory barriers lead to cellular damage. Additionally, CVD manifestations are typically limited to the lower legs because venous return is hindered by anatomical and gravitational forces, especially around the ankle. In addition, clinical severity tends to increase with procedures that occlude venous exit sites, further distorting circulatory dynamics. Genetic influences on the integrity of collagen and elastin contribute importantly to venous wall strength. It also became apparent that the actual primary pathological cause is not valve malfunction but venous wall weakness. Polidocanol addresses this by targeting venous wall instability, highlighting that varicose (dilated) veins are a symptom, not the disease itself. It has a superior safety profile compared to agents like sodium tetradecyl sulphate and hypertonic saline and hence is a preferred choice for treating haemorrhoidal disease, oesophageal varices, telangiectasias, lymphovenous malformations, and CVD. Polidocanol use is associated with a very low incidence of complications, and the development of foam formulations has further enhanced its efficacy by improving retrograde flow dynamics. During sclerotherapy, forceful injection of polidocanol can cause intervention with plasma proteins, increasing its foam stability and therapeutic effectiveness.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"645-674"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480129","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":"Antiseizure Medications that Did Not Reach the Epilepsy Market: An Assessment of Factors Contributing to Their Failed Clinical Development Over the Last Three Decades.","authors":"Meir Bialer, Emilio Perucca","doi":"10.1007/s40265-026-02297-y","DOIUrl":"10.1007/s40265-026-02297-y","url":null,"abstract":"<p><p>The EILAT Conferences on New Antiepileptic Drugs (AEDs), which have taken place biennially since 1992, have traditionally offered a forum for stakeholders from industry and academia to present updates on potential antiseizure medications (ASMs) in development. We reviewed publicly accessible data on compounds that were presented at EILAT conferences over this period but failed to reach the ASM market. The overarching aim was to determine the most likely reason(s) for terminating development and to provide potentially useful clues to improve the efficiency of ASM development in the future. We restricted our analysis to investigational compounds in clinical development that targeted common epilepsies. Of 56 such compounds, 15 reached the ASM market, 11 are still in development, and 30 had their development for epilepsy indications terminated. Compounds whose development was terminated include atimepazole, beprodone, cannabidivarin, carabersat, conantokin-G, dezinamide, elpetrigine, flunarizine, fluorofelbamate, ICA-105665, isovaleramide, JNJ-40411813, losigamone, naluzotan, padsevonil, pitolisant, ralitoline, remacemide, safinamide, soretolide, talampanel, tonabersat, T2000, T2007, valnoctamide, valrocemide, VX-765, zandatrigine, zuranolone, and 534U87. For most of these compounds, termination of development occurred during phase 1 or phase 2. Unfavorable pharmacokinetic properties, such as short half-life or high drug-drug interaction potential, were a common likely cause of early termination. Overall, the most common reason for terminating clinical development was lack of efficacy, possibly related, at least in some cases, to use of suboptimal trial designs. Review of preclinical data suggested that, for many compounds, suboptimal clinical efficacy was unlikely to be primarily explained by their mechanism of action. In some instances, failure to pursue an epilepsy indication could be explained by prioritization of development for other neurological or psychiatric conditions. This may reflect the perception of the drug market for common epilepsies being relatively crowded, and only attractive for compounds with outstanding safety or efficacy advantages over existing medications.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"599-625"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325142","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":"Metabolic Dysfunction-Associated Steatohepatitis (MASH)-Cirrhosis Clinical Trials: Lessons Learned and Future Directions.","authors":"Rashmee Patil, Winston Dunn, Mazen Noureddin, Naim Alkhouri","doi":"10.1007/s40265-026-02301-5","DOIUrl":"10.1007/s40265-026-02301-5","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH)-cirrhosis represents a critical and growing global health burden due to its progression to hepatic decompensation, hepatocellular carcinoma (HCC), and liver-related mortality. A growing number of MASH-related HCCs contribute to the increasing need for liver transplantation. Under current regulatory guidance, Phase 3 trials in compensated MASH cirrhosis compare drug versus placebo on time to a composite endpoint for outcomes. Composite endpoints are major adverse liver outcomes (MALO)-hepatic decompensation (ascites requiring treatment, variceal hemorrhage, hepatic encephalopathy, MELD ≥ 15), liver transplantation-and all‑cause mortality. Future trial sample size hinges on the annual event rate and expected effect size. From prior studies, event rates are ~ 3-20% higher with risk features. Progression to large gastroesophageal varices is now an accepted endpoint and will typically add a 3-5% yearly event rate to the baseline MALO event rate. Effect sizes on hard outcomes in metabolic chronic diseases often range from 0.70-0.85. Trials should enroll high‑risk patients (defined as those with clinically significant portal hypertension [CSPH], Child Turcotte Pugh A cirrhosis, and magnetic resonance elastography measurements > 6.5 kPa), plan 3-5 years of follow‑up and enroll using noninvasive criteria. Accelerated approval based on histologic reversal of cirrhosis is potentially possible; the SYMMETRY Phase 2b trial achieved F4 regression within 96 weeks with efruxifermin. Levers to increase regression include an upper limit for liver stiffness measurement(LSM), a platelet threshold (> 110,000/µL), limiting CSPH, and prespecified proportions with FIB‑4 > 3.5 or enhanced liver fibrosis (ELF) > 11.3. Ongoing studies include but are not limited to survodutide, a glucagon/GLP-1 receptor dual agonist targeting metabolic drivers, efruxifermin, an FGF21 analog, and a conditionally approved drug resmetirom, which is a selective thyroid hormone receptor β agonist.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"627-643"},"PeriodicalIF":14.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456420","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":"Treating Pancreatic Ductal Adenocarcinoma: The Targeted Revolution is Here.","authors":"Michael S May, Wungki Park, Eileen M O'Reilly","doi":"10.1007/s40265-026-02295-0","DOIUrl":"10.1007/s40265-026-02295-0","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is a rising cause of morbidity and mortality. An immunosuppressive, hostile tumor microenvironment, and KRAS-driven biology have contributed to poor outcomes in PDAC. Recent breakthroughs in targeting tumors with homologous repair deficiency, KRAS^G12C mutations, rare gene fusions, and other molecular abnormalities have improved outcomes in subsets of patients. KRAS inhibitors, both allele specific and pan(K)RAS, claudin-targeting biologics, and PRMT5 inhibitors have demonstrated single agent activity in pretreated, biomarker selected PDAC. An improved understanding of the tumor immune microenvironment has facilitated the development of promising cancer vaccines and immunomodulating agents. This review summarizes the current state of PDAC therapeutics and describes drug development targets that will transform outcomes in PDAC in the proximate future.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"507-532"},"PeriodicalIF":14.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275760","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}