Drugs最新文献

{"title":"Small-Cell Lung Cancer: Biology, Translational Science and Clinical Innovation.","authors":"Shrey Sindhwani, Miles Thomas, Kanika Gehlaut, Harveen Kaur, Waqas Haque, Aditya Juloori, Noura J Choudhury","doi":"10.1007/s40265-026-02353-7","DOIUrl":"10.1007/s40265-026-02353-7","url":null,"abstract":"<p><p>Small-cell lung cancer (SCLC) is widely considered one of the most aggressive human malignancies, characterized by development of rapid metastases and eventual resistance to platinum chemotherapy and immunotherapy. For decades, despite rigorous scientific investigation and well-established mouse models providing a basis for mechanistic understanding, there were limited therapeutic advances for SCLC. The past decade has seen reinvigoration of drug development for SCLC as well as US Food and Drug Administration (FDA) approval of tarlatamab, a bispecific T-cell engager with unprecedented survival advantage in this recalcitrant disease. Multiple other promising clinical trials in the first and later-line settings are underway that seek to challenge standards of first-line chemoimmunotherapy, investigate combination treatments in the later line, and introduce T-cell engagers earlier in treatment. This review provides a comprehensive primer on the biology and molecular landscape of SCLC, in the context of how both shape ongoing investigational strategies. A broad overview of established multidisciplinary management of both limited-stage and extensive-stage SCLC is discussed to provide understanding of how the next decade is likely to bring significant clinical gains as emerging therapeutics seek to redefine the management of SCLC and build upon novel advances.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1513-1533"},"PeriodicalIF":14.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688626","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":"The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.","authors":"Victor Abiola Adepoju, Abdulrakib Abdulrahim, Shankar Biswas","doi":"10.1007/s40265-026-02359-1","DOIUrl":"10.1007/s40265-026-02359-1","url":null,"abstract":"<p><p>Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with ≥ 99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1411-1420"},"PeriodicalIF":14.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387550","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":"Ecnoglutide: First Approvals.","authors":"Matt Shirley","doi":"10.1007/s40265-026-02350-w","DOIUrl":"10.1007/s40265-026-02350-w","url":null,"abstract":"<p><p>Ecnoglutide is a cyclic adenosine monophosphate (cAMP)-biased glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Sciwind Biosciences for the treatment of type 2 diabetes mellitus (T2DM) and for use in long-term weight management. In January 2026, subcutaneous ecnoglutide received its first approval, in China, for use in glycaemic control in adults with T2DM. Subsequently, in March 2026, ecnoglutide received approval in China for use (in combination with diet control and increased physical activity) in long-term weight management in adults with obesity or with overweight with one or more weight-related comorbidity. Ecnoglutide is also under clinical evaluation for use in adolescents with obesity, and in adults with obesity and obstructive sleep apnoea and adults with obesity and knee osteoarthritis. An oral tablet formulation of ecnoglutide is in clinical development. This article summarises the milestones in the development of ecnoglutide leading to these first approvals for T2DM and long-term weight management.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1563-1570"},"PeriodicalIF":14.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395832","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":"DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.","authors":"Giovanna Pecoraro, Alberto De Giorgi, Giulia Montelatici, Giuseppe Salfi, Hui-Ming Lin, Fabio Turco, Tarek Taha, Himisha Beltran, Johann de Bono, Rahul Raj Aggarwal, Gunhild von Amsberg, Markus Joerger, Martina Imbimbo, Ilaria Colombo, Silke Gillessen, Martino Pedrani","doi":"10.1007/s40265-026-02355-5","DOIUrl":"10.1007/s40265-026-02355-5","url":null,"abstract":"<p><p>Inhibition of androgen receptor (AR) signaling remains the cornerstone of systemic therapy for advanced prostate cancer (PC). However, a subset of aggressive tumors either arises de novo with neuroendocrine features or emerges under treatment pressure through lineage plasticity and AR independence. These lethal states are encompassed within the spectrum of aggressive-variant prostate cancer (AVPC), an umbrella term that includes both histologically confirmed neuroendocrine prostate cancer (NEPC)-comprising de novo NEPC and treatment-emergent NEPC (t-NEPC)-and clinically or molecularly defined AVPC lacking histologic confirmation but sharing neuroendocrine-like, AR-indifferent, or small-cell features. These phenotypes are characterized by rapid progression, visceral dissemination, low or discordant prostate-specific antigen (PSA) levels relative to tumor burden, and poor prognosis. Treatment options for NEPC/AVPC remain limited and largely rely on platinum-based chemotherapy, which usually provides only modest and transient benefit. This unmet need has intensified interest in lineage-associated vulnerabilities. Delta-like ligand 3 (DLL3), an inhibitory Notch ligand with restricted expression in normal adult tissues, is aberrantly upregulated in several neuroendocrine malignancies and has emerged as a clinically actionable target. In prostate cancer, DLL3 expression is enriched in neuroendocrine tumor cells, being detected in approximately 76.6% of castration-resistant NEPC compared with only 12.5% of castration-resistant adenocarcinoma, supporting its development as both a biomarker and therapeutic vulnerability. Clinical success of DLL3-targeted therapies in small-cell lung cancer further supports evaluation of DLL3-directed strategies in NEPC and related AVPC states. This review summarizes the biological rationale, translational evidence, and emerging clinical data supporting DLL3-targeted therapies in prostate cancer. Investigational platforms include antibody-drug conjugates, bispecific and trispecific T-cell engagers, and DLL3-directed radiopharmaceuticals. Early clinical studies suggest that activity is largely confined to DLL3-expressing neuroendocrine tumors, highlighting the importance of biomarker-guided patient selection. Delta-like ligand 3-directed therapies may reshape the management of DLL3-expressing prostate cancer if ongoing efforts to refine biomarkers improve patient enrichment and optimize trial design are successfully translated into clinical practice.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1489-1511"},"PeriodicalIF":14.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618769","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":"Emerging Strategies Targeting the PI3K/AKT/mTOR Pathway in HR+/HER2- Advanced Breast Cancer.","authors":"Lan Lei, Madison Canning, Elizabeth Sakach, Almeera Lateef, Larisa Kamga, Minaam Abid, Kevin Kalinsky, Shipra Gandhi","doi":"10.1007/s40265-026-02347-5","DOIUrl":"10.1007/s40265-026-02347-5","url":null,"abstract":"<p><p>Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer accounts for approximately 70% of breast cancer cases. Despite recent advances with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), resistance inevitably develops, often driven by activation of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. Genetic alterations such as PIK3CA mutations (present in ~ 45% of HR+/HER2- tumors), AKT1 mutations, and PTEN loss contribute to endocrine resistance and poor outcomes. This review summarizes emerging strategies targeting this pathway to overcome resistance in advanced disease. Isoform-specific PI3K inhibitors, including alpelisib and inavolisib, have demonstrated clinically meaningful progression-free survival benefits in PIK3CA-mutated populations, with inavolisib showing improved tolerability and efficacy. In contrast, pan-PI3K inhibitors such as buparlisib have been constrained by toxicity. Targeting downstream signaling, AKT inhibitors have also shown benefit: capivasertib has demonstrated clinical efficacy leading to US Food and Drug Administration approval, while ipatasertib has yielded encouraging results, particularly in tumors harboring PIK3CA, AKT1, or PTEN alterations. Mammalian target of rapamycin inhibitors, notably everolimus, have shown efficacy irrespective of mutation status. The dual PI3K-mTOR inhibitor (gedatolisib) has also shown promising progression-free survival benefit in a PIK3CA wild-type population. Next-generation agents, including mutant-selective PI3Kα inhibitors and bi-steric mTOR complex 1 inhibitors, are under active investigation. Optimal sequencing of these agents alongside endocrine therapy and CDK4/6i options remain a critical question, as does integration of genomic testing to guide therapy. Future directions include rational combination strategies, improved biomarker-driven selection, and novel modalities such as proteolysis-targeting chimeras (PROTACs). Collectively, these advances aim to enhance durability of response, minimize toxicity, and improve survival in HR+/HER2- metastatic breast cancer.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1471-1487"},"PeriodicalIF":14.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600275","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":"Vepdegestrant: First Approval.","authors":"Simon Fung","doi":"10.1007/s40265-026-02372-4","DOIUrl":"https://doi.org/10.1007/s40265-026-02372-4","url":null,"abstract":"<p><p>Vepdegestrant (VEPPANU; formerly ARV 471) is a novel PROteolysis TArgeting Chimera (PROTAC) that is able to simultaneously bind the estrogen receptor (ER) and an E3 ubiquitin ligase complex, resulting in polyubiquitination of the ER and its subsequent degradation via a proteasome. It is being developed by Arvinas and Pfizer primarily as a treatment for ER+, HER2- breast cancer. In May 2026, vepdegestrant received its first global approval in the USA for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. This article summarizes the milestones in the development of vepdegestrant leading to its first approval in this indication.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849581","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":"Andamertinib: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-026-02375-1","DOIUrl":"https://doi.org/10.1007/s40265-026-02375-1","url":null,"abstract":"<p><p>Andamertinib (^®) is a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) being developed by Beijing Avistone Biotechnology for the treatment of non-small cell lung cancer (NSCLC). On 30 April 2026, andamertinib received conditional approval in China for adult patients with locally advanced or metastatic NSCLC who have experienced disease progression during or following platinum-based chemotherapy, or who are intolerant to platinum-based chemotherapy, and who have been confirmed by testing to have an EGFR exon 20 insertion mutation. This article summarizes the milestones in the development of andamertinib leading to this first approval for NSCLC.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789620","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":"Developmental Progress and Future Potential for Inhaled Biologics in the Treatment of Respiratory Diseases.","authors":"Bhupendra Raj Giri, Jamie Erin Spahn, Rawidh Alsaidalani, Beatriz Behrend-Keim, Mohammed Bhia, Jailen Haley Doyle, Matthew Joseph Herpin, Rex Corbin Moore, Nila Sangeetha Murali, Arifenur Safak, Hugh David Charles Smyth","doi":"10.1007/s40265-026-02336-8","DOIUrl":"10.1007/s40265-026-02336-8","url":null,"abstract":"<p><p>Inhaled biologics to treat lung diseases have an extensive history. This is counterbalanced by the limited products that have reached the commercialization stage of development despite the numerous disease states and targets that may be suitable for the delivery of proteins, peptides, or nucleic acid therapeutics. These opportunities are reviewed alongside current and past clinical and preclinical studies that highlight both successful and discontinued programs, providing key lessons for future development. Although there are physical, biological, and technical barriers that must be overcome to successfully deliver these relatively fragile moieties to the lung, there are commercial and clinical reasons why success has not always been realized. This review captures the current landscape of inhaled biologics, and as the field advances, we expect the inhaled route to expand rapidly given its distinct pharmacokinetic advantages for local lung diseases.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1187-1229"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294008","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":"Navepegritide: First Approval.","authors":"Connie Kang","doi":"10.1007/s40265-026-02341-x","DOIUrl":"10.1007/s40265-026-02341-x","url":null,"abstract":"<p><p>Navepegritide (YUVIWEL^®) is a prodrug of C-type natriuretic peptide (CNP) developed by Ascendis Pharma for the treatment of achondroplasia and is being investigated for hypochondroplasia. Navepegritide is administered once weekly and designed to provide sustained release and continuous exposure of active CNP, which is needed to counteract the overactive fibroblast growth factor receptor 3 signaling in achondroplasia, resulting in improved growth velocity. Navepegritide recently received accelerated approval in the USA for increasing linear growth in paediatric patients aged ≥ 2 years with achondroplasia with open epiphyses. This article summarizes the milestones in the development of navepegritide leading to this first approval for achondroplasia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1385-1391"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149120","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":"Emerging Cardiorenal Protective Therapies in Lupus Nephritis.","authors":"Irene Martin Capon, Justo Sandino-Pérez, María Galindo, Enrique Morales","doi":"10.1007/s40265-026-02337-7","DOIUrl":"10.1007/s40265-026-02337-7","url":null,"abstract":"<p><p>Lupus nephritis (LN) remains a major cause of morbidity and progression to chronic kidney disease in systemic lupus erythematosus. Beyond immunosuppression, emerging evidence highlights the critical role of nephron-protective therapies in mitigating chronic damage and preserving renal function. This narrative review included a structured literature search in PubMed, EMBASE, and Web of Science for new cardio-renoprotective therapies in LN. Agents targeting metabolic, hemodynamic, and inflammatory pathways, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), have shown renal and cardiovascular benefits in proteinuric and diabetic populations, and recent data suggest potential efficacy in LN. These therapies reduce intraglomerular pressure, proteinuria, oxidative stress, and tubular inflammation, complementing the immunomodulatory effects of standard regimens. In addition, endothelin receptor antagonists and novel anti-fibrotic or metabolic modulators are under investigation for synergistic cardiorenal protection. Early integration of these agents may delay progression to end-stage kidney disease, improve systemic vascular health, and reduce long-term treatment burden. Future randomized trials specifically designed in LN cohorts are warranted to define optimal timing, combinations, and safety in the context of immunosuppression. Nephron-protective therapy represents a paradigm shift in LN management, from solely controlling autoimmunity toward preserving long-term renal structure and function through multi-system, cardio-renal protection.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1171-1185"},"PeriodicalIF":14.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940522","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}