Drugs最新文献

{"title":"Reframing the High-density Lipoprotein (HDL) Hypothesis in Light of Clinical Trials of Cholesterol Ester Transfer Protein (CETP) Inhibitors.","authors":"Michael J Chehade, Michael J Haas, Arshag D Mooradian","doi":"10.1007/s40265-026-02338-6","DOIUrl":"10.1007/s40265-026-02338-6","url":null,"abstract":"<p><p>High-density lipoprotein cholesterol (HDL-C) has been inversely associated with atherosclerotic cardiovascular disease (ASCVD) risk. This relationship is the foundation of the \"HDL hypothesis,\" which states that increasing plasma HDL-C levels would result in a decrease in cardiovascular events. The recent surge in clinical testing of cholesteryl ester transfer protein (CETP) inhibitors provides valuable data for this hypothesis. The CETP inhibitors increase plasma HDL-C along with variable effects on low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). The clinical outcomes of randomized controlled trials were heterogeneous, with several studies showing either neutral or adverse clinical outcomes despite robust increases in HDL-C values. These observations along with Mendelian randomization studies suggest that low HDL-C is a risk marker, not a causal mediator of ASCVD. New evidence points to HDL functionality, specifically cholesterol efflux potential and particle composition, instead of HDL-C concentration as a more relevant determinant of ASCVD risk. The favorable clinical outcomes observed with certain CETP inhibitors are more consistently explained by reductions in apoB-containing lipoproteins (including LDL-C and non-HDL-C), rather than increases in HDL-C itself. This distinction reframes the HDL hypothesis where HDL-C is merely a biomarker of ASCVD while apoB-containing lipoproteins are the more plausible causal treatment pathway. These findings have shifted the focus of the HDL hypothesis from the \"quantity\" to the \"quality\" of HDL.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1091-1101"},"PeriodicalIF":14.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959825","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":"Antibody-Drug Conjugates in Non-small Cell Lung Cancer.","authors":"Lodovica Zullo, Martina Bortolot, Francesca R Ogliari, Stephanie P L Saw, Robin van Geel, Rob Ter Heine, Anna Sadowska, Jordi Remon, Lizza Hendriks","doi":"10.1007/s40265-026-02331-z","DOIUrl":"10.1007/s40265-026-02331-z","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are complex molecules composed of a monoclonal antibody, a linker and a cytotoxic payload. Their design enables the selective delivery of cytotoxic agents to tumoral cells through antibody binding to a tumor-expressed antigen, followed by internalization, intracellular degradation and payload release, ultimately enabling the cytotoxic drug to exert its antitumor activity. ADCs have been evaluated in phase II and III trials in previously treated advanced non-small cell lung cancer (NSCLC), both in oncogene-addicted and in non-oncogene-addicted tumors, addressing resistance to standard therapies. Ongoing clinical trials are now expanding their use both in the first-line setting for advanced disease and in earlier disease stages. This narrative review summarizes the currently available data for ADC treatment in NSCLC, highlighting the need for improved patient selection to maximize benefit while limiting toxicity, incorporating clinical characteristics, pharmacogenomics and optimal treatment sequencing in the equation. Moreover, the understanding of resistance mechanisms and the development and validation of predictive biomarkers will be of utmost relevance to inform clinical practice.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1045-1073"},"PeriodicalIF":14.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971254","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":"Malaria Prevention: Progress to Date.","authors":"Martin P Grobusch, Jenny L Schnyder, Patricia Schlagenhauf, Hanna K de Jong, Thomas Hanscheid","doi":"10.1007/s40265-026-02318-w","DOIUrl":"10.1007/s40265-026-02318-w","url":null,"abstract":"<p><p>Chemoprophylaxis (in travellers) and seasonal chemoprophylaxis and preventive treatment (in endemic areas) are important but not exclusive elements of malaria prevention, which hinges on vector repelling in travellers and more comprehensive vector control measures in endemic areas. In malaria-endemic countries, a comprehensive strategy combining drug-based prevention, vaccines and vector control is essential to reduce disease burden. Chemoprophylaxis in endemic settings primarily involves intermittent preventive treatment in vulnerable groups and mass drug administration in communities, rather than continuous daily chemoprophylaxis (as recommended for non-immune travellers). Vaccination has become a groundbreaking addition to the malaria control portfolio in endemic countries. The World Health Organization-endorsed RTS,S/AS01 (Mosquirix^®) and R21/Matrix-M vaccines rolled out in many highly malaria-endemic sub-Saharan African countries, in addition to other malaria control tools, provide overall moderate protection in young children but significantly reduce severe disease and death, and are considered safe. For travellers, malaria vaccines are not available to date. Effort is being put into the development of monoclonal antibodies against malaria as a preventive treatment strategy both to provide protection for the immunocompromised or unvaccinated high-risk individuals before exposure and to disrupt seasonal malaria transmission with a single application. The evolution of malaria preventive tools is a dynamic process, with numerous novel developments on the horizon. For travel medicine indications, further harmonisation of recommendations on the one hand, but also more sophisticated personalisation of recommendations, is envisaged.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"971-988"},"PeriodicalIF":14.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765852","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":"Sonrotoclax: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-026-02322-0","DOIUrl":"10.1007/s40265-026-02322-0","url":null,"abstract":"<p><p>Sonrotoclax (Baiyueda^®), a small-molecule B-cell lymphoma-2 (BCL-2) inhibitor, is being developed by BeOne Medicines for the treatment of various B-cell malignancies. On 6 January 2026, sonrotoclax received conditional approval in China for adult patients with chronic lymphocytic leukaemia (CLL)/small lymphocytic leukaemia (SLL) who have previously received at least one systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor, and adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least two systemic therapies, including a BTK inhibitor. This article summarizes the milestones in the development of sonrotoclax leading to this first approval for the second-line treatment of relapsed/refractory CLL/SLL and MCL.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1153-1163"},"PeriodicalIF":14.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765889","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":"Developments in Pharmacotherapy for Acromegaly: Current and Emerging Approaches.","authors":"Nicholas A Tritos, Beverly M K Biller","doi":"10.1007/s40265-026-02312-2","DOIUrl":"10.1007/s40265-026-02312-2","url":null,"abstract":"<p><p>Pituitary surgery is the primary therapy for most patients with acromegaly. Medical therapy has an important, albeit adjunctive role in the management of patients with persistent disease after surgery. However, primary medical therapy can be appropriate as an option in select patients. Medical therapies in current use for acromegaly are somatostatin receptor ligands (SRLs) (octreotide long-acting release [LAR], octreotide acetate, lanreotide depot, octreotide subcutaneous (SC) depot, pasireotide LAR, oral octreotide, paltusotine), dopamine agonists (cabergoline) and growth hormone receptor antagonists (pegvisomant). These are often efficacious and generally well tolerated. However, a particular pharmaceutical agent may not meet the needs of individual patients because of intolerance, contraindications to their use, lack of sustained efficacy, or decreased quality of life. Several investigational drugs are in development towards addressing unmet needs of patients with acromegaly, including new formulations of SRLs (lanreotide prolonged-release formulation, Debio 4126, pasireotide SC depot), novel SRLs (somatoprim, HTL0030310), monoclonal antibodies against growth hormone, and new growth hormone receptor antagonists. Current and emerging therapies are offering renewed hope for disease control. More studies including comparator agents, identification of accurate biomarkers and models predictive of clinical effectiveness may further improve the care of patients with acromegaly.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"841-850"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662399","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":"Oral Gut-Restricted Targeted Therapy for IBD: A Pipeline Review.","authors":"Joana Roseira, Marianne Hupé, Yuhong Yuan, Fernando Magro, Vipul Jairath","doi":"10.1007/s40265-026-02309-x","DOIUrl":"10.1007/s40265-026-02309-x","url":null,"abstract":"<p><p>Oral gut-restricted therapies are being explored as a drug delivery strategy for inflammatory bowel disease (IBD), with the aim of achieving therapeutic effects within the intestinal mucosa while minimizing systemic exposure. Advances in molecular engineering and formulation technologies have enabled the development of orally administered agents intentionally designed to act locally within the gastrointestinal tract. This narrative review examines the biological, pharmacokinetic, and formulation principles underlying oral gut-restricted drug delivery in IBD, including an analysis of discontinued clinical development programs in ulcerative colitis and Crohn's disease. Across locally acting antibodies, peptides, and small molecules, the analysis of these programs reveals recurring factors contributing to discontinuation. These include limited or absent clinical efficacy despite evidence of mucosal target engagement, challenges in achieving consistent and adequate intestinal exposure, constraints related to formulation or delivery technologies, and trial-related factors such as high placebo response rates. In several cases, manufacturing variability or strategic considerations also influenced development outcomes. The review of the current clinical trial pipeline suggests an evolution in development strategies relative to earlier programs, with increasing emphasis on the confirmation of local tissue drug levels, incorporation of mucosal pharmacodynamic readouts, and selection of endpoints aligned with localized mechanisms of action, including endoscopic and histologic outcomes. These elements appear critical for interpreting early phase efficacy signals for agents designed to have minimal systemic activity. Effective translation requires alignment between mechanism of action, intestinal drug delivery, tissue-level pharmacodynamics, and clinical trial design. Incorporating these lessons may improve the likelihood of success for future oral gut-restricted therapies in IBD.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"779-795"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590778","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":"Current and Emerging Biologic Therapies for Severe Asthma.","authors":"Mario Cazzola, Maria Gabriella Matera, Josuel Ora, Luigino Calzetta, Paola Rogliani","doi":"10.1007/s40265-026-02310-4","DOIUrl":"10.1007/s40265-026-02310-4","url":null,"abstract":"<p><p>Severe asthma is a heterogeneous disorder characterized by persistent symptoms, frequent exacerbations, and corticosteroid dependence despite optimized therapy. Seven monoclonal antibodies are currently approved, targeting immunoglobulin E (IgE; omalizumab), interleukin (IL)-5 or IL-5 receptor α (mepolizumab, reslizumab, depemokimab, benralizumab), IL-4 receptor α (dupilumab), and the epithelial alarmin thymic stromal lymphopoietin (TSLP; tezepelumab). These therapies have demonstrated substantial reductions in exacerbation rates and oral corticosteroid use, along with improvements in lung function and patient-reported outcomes. Safety profiles are generally favorable across populations. Key predictors of response include blood eosinophil counts, fractional exhaled nitric oxide, and phenotype-specific biomarkers. Despite these advances, unmet needs remain. Current biologics only partially address type 2-low, neutrophilic, and mixed granulocytic phenotypes, as well as airway remodeling and persistent exacerbations in type 2-high patients. Emerging strategies aim to overcome these limitations by targeting upstream alarmins (TSLP and IL-33), dual or trispecific cytokine pathways, and IgE-producing B cells. Novel Fc-engineered and dual-receptor anti-IgE monoclonal antibodies enhance the magnitude and durability of IgE suppression. Multi-target constructs, including bispecific and trispecific agents, simultaneously block overlapping type 2 and non-type 2 pathways, which could improve outcomes in heterogeneous and refractory populations. Preclinical and early-phase clinical studies suggest that these approaches may provide disease-modifying effects and support biomarker-guided personalized therapy. This review summarizes the current landscape of approved biologics and the rationale for next-generation therapies in severe asthma. It highlights mechanistic insights, clinical efficacy, and future directions for precision-targeted treatment strategies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"813-840"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572813","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":"Aficamten: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40265-026-02307-z","DOIUrl":"10.1007/s40265-026-02307-z","url":null,"abstract":"<p><p>Aficamten (MYQORZO™) is a small-molecule cardiac myosin inhibitor being developed by Cytokinetics for the treatment of hypertrophic cardiomyopathy (HCM). Supported by the findings of the phase III, randomised, double-blind, placebo-controlled SEQUOIA-HCM trial, in December 2025 aficamten was approved in both China and the USA to improve functional capacity and symptoms in adults with symptomatic obstructive HCM (oHCM). Subsequently, in February 2026, aficamten was also approved in the EU for the treatment of symptomatic oHCM in adult patients. Aficamten is also in phase III evaluation for use in the treatment of non-obstructive HCM (nHCM) in adults. This article summarises the milestones in the development of aficamten leading to this first approval for symptomatic oHCM.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"949-956"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621775","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 Role of β-Blockers in the Evolving Treatment Landscape of Resistant Hypertension.","authors":"Stefano Masi, Atul Pathak, Rosa Maria Bruno, Sofie Brouwers, Krzysztof Narkiewicz, Stefano Taddei, Konstantinos Tsioufis, Reinhold Kreutz","doi":"10.1007/s40265-026-02319-9","DOIUrl":"10.1007/s40265-026-02319-9","url":null,"abstract":"<p><p>Resistant hypertension (RHTN) is estimated to affect approximately 15% of all patients with hypertension, although its reported prevalence varies according to the blood pressure (BP) thresholds used for diagnosis, the criteria applied to exclude secondary or pseudoresistant hypertension, and the characteristics of the study populations. Regardless of its current prevalence, RHTN is expected to be encountered with increasing frequency in routine clinical practice, driven by the rising prevalence of conditions that are directly or indirectly linked with its increased risk, such as obesity, diabetes mellitus, and chronic kidney disease (CKD). Consequently, recent clinical trials and hypertension guidelines have devoted substantial attention to RHTN, also considering its association with an increased risk of cardiovascular events and renal failure. In this narrative review, we summarize mechanistic insights and evidence from randomized clinical trials and real-world studies, as well as recommendations from current international guidelines, to provide an updated perspective on the management of RHTN. Among multiple systems, activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system represents a central pathophysiological mechanism in RHTN, promoting sodium retention and vascular dysfunction. β-blockers counteract SNS overactivity, a target mechanism not addressed by other first-line therapies, and have compelling indications in most comorbidities associated with RHTN, including coronary artery disease, heart failure, and atrial fibrillation. They can be used across diverse patient populations, including those with advanced CKD, and their side effects can be readily monitored and managed. Evidence from randomized trials and real-world studies supports their efficacy, tolerability, and safety even in high-risk populations. Emerging strategies, including a quadruple single-pill combination containing a β-blocker, may enhance adherence, optimize BP control, and simplify RHTN management.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"887-907"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722182","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":"Advances in Immune-Based Approaches for the Cure of HIV Infection.","authors":"Julia A Wagner, Demi A Sandel, Amelia N Deitchman, Rachel L Rutishauser, Steven G Deeks, Michael J Peluso","doi":"10.1007/s40265-026-02311-3","DOIUrl":"10.1007/s40265-026-02311-3","url":null,"abstract":"<p><p>Despite significant advances in antiretroviral therapy, the need for a cure for HIV persists because of factors such as long-term antiretroviral therapy-related comorbidities, disease stigma, and inequities in access to care. Most cure efforts focus on inducing durable HIV remission (antiretroviral therapy-free viral control) either by augmenting immune function or reducing the HIV reservoir. In this review, we highlight immune-based cure interventions currently under investigation with a particular focus on those that have demonstrated the ability to induce durable HIV remission after analytic treatment interruption, here termed \"post-intervention control\". While current cure interventions are generally complex, expensive, and not easily scalable, they provide critical \"proof of principle\" that a cure for HIV is possible. Continuing to make studies of HIV cure a funding priority is important, we believe, as continued optimization of cure interventions should eventually lead to a cure that is simple, safe, effective, affordable, and scalable. In addition, we highlight critical features in clinical trial design and pharmacokinetics/pharmacodynamics that should be considered prior to clinical trial implementation.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"851-870"},"PeriodicalIF":14.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812340","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}