BioDrugs最新文献

{"title":"Mirikizumab as Induction and Maintenance Therapy in Chinese Patients with Ulcerative Colitis: A Subpopulation Analysis of the Randomized, Global Phase 3 LUCENT-1 and LUCENT-2 Trials.","authors":"Zhihua Ran, Yan Chen, Yinglei Miao, Yufang Wang, Xiang Gao, Jie Zhong, Xueli Ding, Chengdang Wang, Xiaolan Zhang, Yijuan Ding, Naizhong Hu, Dan Tang, Jiao Yu, Chenxi Qian, Jun Shen","doi":"10.1007/s40259-026-00776-y","DOIUrl":"10.1007/s40259-026-00776-y","url":null,"abstract":"<p><strong>Background: </strong>Mirikizumab, a p19-directed anti-interleukin-23 antibody, demonstrated efficacy in patients with moderately-to-severely active ulcerative colitis in the global phase 3 LUCENT-1 induction (NCT03518086) and LUCENT-2 maintenance (NCT03524092) trials.</p><p><strong>Objective: </strong>The aim was to conduct a pre-specified Chinese subpopulation analysis of LUCENT-1 and LUCENT-2.</p><p><strong>Methods: </strong>In LUCENT-1, patients were randomized 3:1 to mirikizumab 300 mg or placebo intravenously every 4 weeks (Q4W) for 12 weeks. In LUCENT-2, patients with a clinical response to mirikizumab at week 12 of LUCENT-1 were re-randomized 2:1 to mirikizumab 200 mg or placebo via subcutaneous injection Q4W for 40 weeks. The primary endpoint in both trials was clinical remission at study end, defined as a Mayo stool frequency subscore of 0, or 1 with a ≥ 1-point decrease from baseline, rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 (excluding friability).</p><p><strong>Results: </strong>Among 183 Chinese patients included in the LUCENT-1 induction trial, clinical remission rates at week 12 were higher with mirikizumab 300 mg (n = 140) versus placebo (n = 43) (18.6% vs. 7.0%; common risk difference 11.5%). Among 80 patients who responded to mirikizumab and underwent randomization again in the LUCENT-2 maintenance trial, clinical remission rates at week 40 were higher with mirikizumab 200 mg (n = 56) versus placebo (n = 24) (50.0% vs. 12.5%; common risk difference 40.4%). During induction and maintenance, the incidence of adverse events was comparable between the mirikizumab and placebo groups.</p><p><strong>Conclusions: </strong>Mirikizumab was effective and well tolerated in the subpopulation of Chinese patients with moderately-to-severely active ulcerative colitis, consistent with the overall trial population.</p><p><strong>Trial registrations: </strong>Clinicaltrials.gov (NCT03518086 and NCT03524092).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"733-745"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen-Directed CAR T-Cell Therapy.","authors":"Maria T Kuipers, Jorne Migchelbrink, Anne Marijn Kramer, Mathilde C M Kouwenhoven, Sonja Zweegman, Kaz Groen, Niels W C J van de Donk","doi":"10.1007/s40259-026-00784-y","DOIUrl":"10.1007/s40259-026-00784-y","url":null,"abstract":"<p><p>B-cell maturation antigen (BCMA) directed CAR T-cell therapy has emerged as an innovative and effective treatment for patients with relapsed/refractory multiple myeloma, demonstrating high response rates and durable remissions. However, its use is associated with a broad spectrum of toxicities, ranging from well characterized common events to rarer, less well described complications. A comprehensive understanding of both common and rare toxicities is essential for timely recognition and management to prevent non-relapse mortality. Frequently observed toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity, and infections. In addition, less frequent adverse events have been reported, including non-ICANS neurotoxicity such as parkinsonian-like movement disorders, immune-mediated enterocolitis, hemophagocytic lymphohistiocytosis, and secondary malignancies. The timing and severity of these toxicities is variable and may be influenced by the extent of CAR T-cell expansion and persistence, as well as patient-specific factors. In this review, we summarize currently available evidence with respect to the safety profile of approved BCMA-targeted CAR T-cell therapies, emphasizing both common and rare toxicities, their possible underlying mechanisms, and management strategies.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"607-621"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant Protein Drugs: A 2025 Update.","authors":"Hèctor López-Laguna, Eloi Parladé, Marianna T P Favaro, Carlos Palacín, Eric Voltà-Durán, Neus Ferrer-Miralles, José Luis Corchero, Rosalía Rodríguez-Rodríguez, Esther Vázquez, Ugutz Unzueta, Antonio Villaverde","doi":"10.1007/s40259-026-00783-z","DOIUrl":"10.1007/s40259-026-00783-z","url":null,"abstract":"<p><p>Over the past decade, recombinant protein therapeutics have moved from conventional biologics toward highly engineered, multifunctional versions. Enabled by innovations in synthetic biology, host cell engineering, and bioprocess optimization, proteins are increasingly viewed not only as drugs for replacement therapies but also as fully versatile platforms in innovative therapeutic approaches aiming at functional reprogramming. Advances in host systems, from optimized microbial strains to mammalian and plant-based platforms, have expanded the range of proteins that can be produced with high fidelity, scalability, and safety. In parallel, modular protein engineering has delivered next-generation formats, including bispecific antibodies, nanobodies, fusion proteins, and self-assembling biomaterials, broadening therapeutic applications across oncology, inflammation, metabolic disorders, and beyond. At the same time, regulatory frameworks are adapting to support accelerated approval of personalized and complex biologics, while decentralized and flexible manufacturing models begin to emerge. This review provides a 2025 update on the field of recombinant protein drugs, integrating advances in production platforms, protein engineering, and regulatory science, and outlining how these technologies are shaping the next generation of biologics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"673-692"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.","authors":"Justin Zhong, Ruijiang Song, Nacim Kerrouche, Xinyu Yu, Yotam Levin, Adam Mor","doi":"10.1007/s40259-026-00785-x","DOIUrl":"10.1007/s40259-026-00785-x","url":null,"abstract":"<p><p>The therapeutic potential of programmed cell death-1 (PD-1) agonism is increasingly recognized as a cornerstone for restoring immune tolerance in autoimmune diseases. However, while PD-1 antagonism has revolutionized oncology, a critical knowledge gap remains regarding optimal strategies to therapeutically harness PD-1 activation. This review provides a comprehensive analysis of the mechanical and molecular requirements for inducing PD-1 signaling, addressing the current lack of a unified framework for agonistic drug development. We first delineate the fundamental biology of PD-1 signaling in maintaining peripheral tolerance. We then evaluate four primary mechanistic strategies currently under investigation: (1) receptor dimerization and clustering; (2) membrane-proximal epitope binding; (3) modulation of antibody binding affinity; and (4) Fcγ-receptor crosslinking. Each mechanism is critically assessed for its ability to mimic natural ligand-induced inhibitory signaling, alongside its inherent translational limitations. Emerging data suggest that optimal PD-1 agonism is achieved not through high-affinity binding but rather through low-affinity antibodies targeting membrane-proximal epitopes. This approach appears to preserve essential ligand-engagement dynamics and to facilitate productive Fcγ-receptor-mediated scaffolding. By surveying recent advances in clinical trials and ongoing challenges, this work serves as a vital resource for researchers and clinicians. Refinement of these agonistic strategies is essential for the development of next-generation targeted immunotherapies capable of precision immune regulation in chronic autoimmunity.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"567-580"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview and Trend Analysis of Biosimilar Approvals in China.","authors":"Mei Yang, Ning Zhang, Haixue Wang","doi":"10.1007/s40259-026-00788-8","DOIUrl":"10.1007/s40259-026-00788-8","url":null,"abstract":"<p><p>Biosimilars are a critical strategy for improving access to high-cost biologics and ensuring the sustainability of healthcare systems worldwide. Over the past decade, China has transformed from a nascent market into one of the world's most active regions for biosimilar development. This review evaluates this transformation with a focus on regulatory evolution, approval dynamics, and global integration. We trace the development of China's biosimilar regulatory framework from the foundational 2015 Technical Guidelines to the current system of 19 technical and product-specific guidelines, highlighting the maturation of a stepwise, science-driven comparability paradigm aligned with international regulatory standards. Drawing on a systematic analysis of 83 biosimilars approved between 2019 and 2025, we analyze trends across molecular classes, therapeutic areas, and regulatory review pathways, illustrating how regulatory expectations and sponsor development strategies have evolved through representative case examples. Notably, the 2025 annual reports from both the US Food and Drug Administration and European Medicines Agency emphasize the increasing number of biosimilar approvals, therefore, we place China's approval experience in brief comparative context. Finally, we discuss China's expanding biosimilar development pipeline in the context of the forthcoming global biologics patent cliff and ongoing international initiatives to streamline biosimilar development, highlighting China's increasing integration into the global biopharmaceutical landscape.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"599-606"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA Vaccines for Influenza: Hope for a Universal Vaccine?","authors":"Priscilla Omotara, Wandi Zhu, Bao-Zhong Wang","doi":"10.1007/s40259-026-00791-z","DOIUrl":"10.1007/s40259-026-00791-z","url":null,"abstract":"<p><p>Seasonal influenza epidemics and pandemics remain a persistent public health threat. A universal influenza vaccine is urgently needed. Such a vaccine must accommodate rapid viral evolution, strain diversity-including types A and B and their many subtypes-and the complexities of human immune history and biases. Messenger RNA (mRNA)-formulated lipid-nanoparticles have evolved from an emergency pandemic vaccine experiment into a versatile vaccine platform. This technology has demonstrated potential to address several critical challenges in developing a universal influenza vaccine, including rapid strain updates, the production of high-valent formulations, and the ability to target conserved antigens that may induce broader and longer-lasting protection. This review summarizes recent studies and applications of multivalent antigen selection strategies and self-amplifying and circular RNA vaccine platforms to develop mRNA influenza vaccines to achieve vaccine universality, with an emphasis on immune responses against conserved targets. We also review the latest advances in generating long-term mucosal immunity against influenza through optimized mRNA delivery. Finally, we discuss practical considerations for correlates of protection, manufacturing, and accessibility, pioneering mRNA vaccine candidates heading to clinical trials, and milestones that define vaccine \"universality.\"</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"581-597"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.","authors":"Matthew J Slarve, Christine Tkaczyk, Michael P Doyle, Timothy J Break, Alexander B Smith, Galit Alter, Brian Luna, Brad Spellberg, Antonio DiGiandomenico","doi":"10.1007/s40259-026-00787-9","DOIUrl":"10.1007/s40259-026-00787-9","url":null,"abstract":"<p><p>The ever-increasing trend of antibiotic resistance necessitates new therapeutic strategies for fighting infection. Standing on decades of extensive research and development, monoclonal antibodies have great promise for treating antibiotic-resistant bacterial infections. In this comprehensive review of the field, we summarize the rapidly emerging field of monoclonal therapeutics that offer alternative approaches to target bacterial pathogens that pose critical concern to human health. Organizing the findings by species and by molecular target, we discuss antibodies that have demonstrated therapeutic potential as well as those that did not provide efficacy, highlighting new insights for the design and discovery of highly effective therapeutics for the future. Furthermore, we discuss the latest advances in molecular biology that have revolutionized the implementation, efficacy, and utility of monoclonal antibodies as therapeutics, and that continues to drive what will be an exciting era for antibacterial monoclonal antibodies.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"641-671"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Mirikizumab as Induction and Maintenance Therapy in Chinese Patients with Ulcerative Colitis: A Subpopulation Analysis of the Randomized, Global Phase 3 LUCENT-1 and LUCENT-2 Trials.","authors":"Zhihua Ran, Yan Chen, Yinglei Miao, Yufang Wang, Xiang Gao, Jie Zhong, Xueli Ding, Chengdang Wang, Xiaolan Zhang, Yijuan Ding, Naizhong Hu, Dan Tang, Jiao Yu, Chenxi Qian, Jun Shen","doi":"10.1007/s40259-026-00793-x","DOIUrl":"10.1007/s40259-026-00793-x","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"759-761"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?","authors":"Capucine Arrivé, Marie Hotot, Jean-François Jourdil, Françoise Stanke-Labesque","doi":"10.1007/s40259-026-00790-0","DOIUrl":"10.1007/s40259-026-00790-0","url":null,"abstract":"<p><p>The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date synthesis on the pharmacological targets of biologics used in kidney transplantation, (2) assesses the interindividual variability of the pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of key biologics, including belatacept, tocilizumab, rituximab, basiliximab, alemtuzumab, eculizumab, ravulizumab, daratumumab, and imlifidase and (3) describes the analytical methods available for their quantification. This review underscores that, although none of these biologics currently meet all criteria for routine therapeutic drug monitoring, emerging clinical evidence indicates that individualized dosing could enhance both therapeutic outcomes and cost effectiveness. It also discusses future directions for improving pharmacokinetic/pharmacodynamic knowledge on biological therapies in kidney transplant recipients and places in perspective the potential of therapeutic drug monitoring to improve the benefit-risk ratio and cost effectiveness of these biologics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"693-712"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Repeated Antigen Exposure on Humoral Tolerance: Antidrug Antibodies After Single-Dose Versus Multi-dose Adalimumab.","authors":"Anika M Valk, Jolinde van Strien, Ninotska Derksen, Dorien Kos, Júlia Castellon Teixell, Jerry Janssen, Floris C Loeff, Lisanne Dijk, Maureen Leeuw, Catherine Smith, Teresa Tsakok, Richard Warren, Nick J Reynolds, Christopher E M Griffiths, Jonathan Barker, Robert Rissman, Wouter Ten Voorde, Justin Jacobse, Daniel Alvarez, Marieke van Ham, Gertjan Wolbink, Anja Ten Brinke, Theo Rispens","doi":"10.1007/s40259-026-00792-y","DOIUrl":"10.1007/s40259-026-00792-y","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic proteins such as adalimumab can elicit an antibody response. How dosing regimens impact immunogenicity remains ill-understood, especially with respect to the frequency of dosing.</p><p><strong>Objective: </strong>We aimed to investigate the relationship between single versus multiple adalimumab doses and immunogenicity, in terms of anti-drug antibody production and skewing towards the non-inflammatory immunoglobulin G4 (IgG4) subclass.</p><p><strong>Methods: </strong>Immunoglobulin M, immunoglobulin G, and IgG4 anti-drug antibodies were analyzed in retrospective cohorts of healthy individuals and patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, or psoriasis, receiving one or multiple doses of adalimumab, using optimized drug-tolerant assays, newly developed in the case of IgG4.</p><p><strong>Results: </strong>A single dose of adalimumab proved highly immunogenic, while repeated dosing, resulting in prolonged exposure to high antigen concentrations, led to attenuation of the anti-drug antibody response. Immunoglobulin G4 anti-drug antibodies developed earlier than previously reported with drug-sensitive assays, appearing as early as week 3, even after a single dose of adalimumab. Skewing towards IgG4 was nevertheless stronger with repeated dosing.</p><p><strong>Conclusions: </strong>Repeated high-dose adalimumab exposure can limit both the magnitude and inflammatory potential of the antibody response. These results highlight drug exposure as a factor modulating the immunogenicity of biologics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"747-757"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}