BioDrugs最新文献

{"title":"Author's Reply to Gonçalves: \"Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review\".","authors":"Chae Sung Lee","doi":"10.1007/s40259-025-00725-1","DOIUrl":"10.1007/s40259-025-00725-1","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"673-674"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315866","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":"Progress and Challenges in the Treatment of Fabry Disease.","authors":"Malte Lenders, Elise Raphaela Menke, Eva Brand","doi":"10.1007/s40259-025-00723-3","DOIUrl":"10.1007/s40259-025-00723-3","url":null,"abstract":"<p><p>Fabry disease is a rare but life-threatening, X-linked, inherited lysosomal storage disorder in which globotriaosylceramide is insufficiently metabolized because of reduced α-galactosidase A activity. Cellular globotriaosylceramide accumulation causes a multisystemic disease, which, if left untreated, reduces life expectancy in female and male individuals by around 10 and 20 years, respectively, leading to progressive renal failure, hypertrophic cardiomyopathy, cardiac arrhythmia, and premature cerebral infarction. The method of choice for confirming the diagnosis is the determination of reduced α-galactosidase A activity in leukocytes in male individuals and the molecular genetic detection of a disease-causing mutation in female individuals. Current approved treatment includes enzyme replacement therapy (agalsidase alfa [0.2 mg/kg body weight], agalsidase beta or pegunigalsidase alfa [both 1.0 mg/kg body weight]) every other week intravenously or, if a responding ('amenable') α-galactosidase A mutation is present, oral pharmacological chaperone therapy (migalastat 123 mg, every other day). Future therapeutic options may include substrate reduction therapy, gene therapy, messenger RNA therapy, and/or vesicle-packaged enzyme replacement therapy. This review presents current and future treatment options with advantages and disadvantages of the different treatment options.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"517-535"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958304","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":"Demand- Versus Supply-Side Policies in Market Penetration of Biosimilars: Which is More Effective?","authors":"Gyeongseon Shin, Heejin Han, Gyeyoung Choi, Donghwan Lee, SeungJin Bae","doi":"10.1007/s40259-025-00721-5","DOIUrl":"10.1007/s40259-025-00721-5","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of demand- and supply-side policies on the biosimilar market penetration and identify effective strategies for promoting biosimilar uptake in eight high-income countries.</p><p><strong>Methods: </strong>We analyzed biosimilar market penetration for infliximab, rituximab, and trastuzumab in six European countries-France, Germany, Italy, Spain, Sweden, and the UK-and two Asian countries-Japan and South Korea. Biosimilar market penetration was measured using two indicators: biosimilar market share and the time required for biosimilars to reach the majority point (> 50% market share). Policies were categorized into demand- and supply-side measures, and weights were applied to reflect the extent and timing of policy implementation. Spearman correlation examined the relationship between policy implementation and biosimilar market penetration.</p><p><strong>Results: </strong>Sweden, Italy, and the UK showed the highest biosimilar market shares, adopting various demand-side policies, while Japan and South Korea exhibited slower biosimilar adoption with fewer or no demand-side policies. Biosimilars in most European countries reached the majority point within 5-6 quarters, while projections for Japan and South Korea exceeded 30 quarters. Correlation analysis revealed that adoption of demand-side policies was significantly associated with higher market share (r_s = 0.69, p < 0.001) and shorter time to reach the majority point (r_s = - 0.62, p < 0.01). In contrast, supply-side policies showed a weaker and less consistent association.</p><p><strong>Conclusions: </strong>Demand-side policies, such as financial incentives and prescribing guidelines, are significantly associated with rapid and widespread biosimilar adoption, while supply-side policies had limited impact. Policymakers should prioritize demand-side measures to improve biosimilar uptake and reduce healthcare expenditures effectively.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"635-644"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965609","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":"Interrogation of Structure-Activity Relationships in Charge Variants of Therapeutic IgG2s Enabled by Free-Flow Isoelectric Focusing Fractionation.","authors":"Lingyu Wang, Yajun Zeng, Wenyuan Gao, Pengcheng Shen, Ping Han, Zhongli Zhang","doi":"10.1007/s40259-025-00718-0","DOIUrl":"10.1007/s40259-025-00718-0","url":null,"abstract":"<p><strong>Background: </strong>Recombinant immunoglobulin G2 (IgG2) antibodies are effective neutralization agents or antagonists with high medical value because of their high specificity, long half-life, and absent effector functions. During biopharmaceutical process development, charge heterogeneity and bioactivity alternation related to charge variation should be investigated to understand the structure-activity relationship (SAR) in therapeutic antibodies. Isoelectric focusing can provide fine resolution for the charge heterogeneity profiling of IgG2, while ion exchange chromatography cannot achieve effective separation of IgG2 charge variants. In-depth investigation of charge heterogeneity requires a fractionation tool to enrich and isolate acidic and basic variants.</p><p><strong>Objectives: </strong>This study aims to investigate the structural origins and functional implications of charge heterogeneity in two therapeutic IgG2 antibodies, including an anti-receptor activator of nuclear factor κ-B ligand (RANKL) biosimilar of denosumab and an innovative anti-CD73 IgG2 (H-mab), using free-flow isoelectric focusing (FF-IEF).</p><p><strong>Methods: </strong>Charge variants of denosumab and H-mab were fractionated using FF-IEF, followed by characterization of isolated IgG2 charge variants to establish the SAR between charge-related antibody modifications and bioactivities. The investigation incorporated in silico 3D modeling of the FcRn-IgG2 Fc complex and the CD73-Fab complex to facilitate the SAR interrogation of these two IgG2s.</p><p><strong>Results: </strong>The acidic charge variants of denosumab were driven primarily by N-glycan sialylation and deamidation in the Fc region, showing negligible effects on biological functions except for a reproducible reduction in FcRn binding affinity. In contrast, the basic charge variants of H-mab were associated with D₉₉-succinimide formation in the heavy chain complementarity-determining region 3 (CDR3), significantly impairing binding and enzymatic inhibition activities.</p><p><strong>Conclusions: </strong>This study underscores the irreplaceable role of FF-IEF in both biosimilar and innovative therapeutic pipelines, highlighting the importance of monitoring charge heterogeneity and understanding SAR in therapeutic IgG2 antibodies.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"621-633"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965614","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":"Characterization of Biosimilar Monoclonal Antibodies and Their Reference Products Approved in Japan to Reveal the Quality Characteristics in Post-approval Phase.","authors":"Hiroko Shibata, Akira Harazono, Masato Kiyoshi, Yoshiro Saito, Akiko Ishii-Watabe","doi":"10.1007/s40259-025-00722-4","DOIUrl":"10.1007/s40259-025-00722-4","url":null,"abstract":"<p><strong>Background: </strong>Promoting the use of biosimilars is a global issue from the perspective of reducing medical costs. In Japan, the replacement of original biopharmaceuticals with biosimilars has not progressed as expected. To promote the use of biosimilar monoclonal antibodies, it is necessary to increase the public's understanding of biosimilars by evaluating and confirming the quality of biosimilar products. However, there are limited data to compare among multiple biosimilars and/or the reference, and among their product lots.</p><p><strong>Objective: </strong>In this study, we evaluated quality attributes of multiple lots of reference products and their biosimilars to determine the extent of distribution in quality attributes between products as well as the quality consistencies from lot to lot.</p><p><strong>Methods: </strong>As the quality attributes, the glycosylation profile, charge heterogeneity, binding affinity for the antigen and Fcγ receptors, and high-molecular-weight species and subvisible particles were measured.</p><p><strong>Results: </strong>The degree of similarity in quality attributes with a reference product was different for each biosimilar product. We confirmed the differences between reference and biosimilar product reported in previous articles or review reports, and that some quality attributes of biosimilars were out of the quality ranges of reference products. Although lot-to-lot variations and trends at some degrees were observed for some products, no clear drifts among lots were observed.</p><p><strong>Conclusion: </strong>Analyzing several lots of these products enabled us to capture a profile of quality characteristics for each product. Overall, the extent of variability of each quality attribute among reference products and biosimilars was revealed by this study for the first time.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"645-667"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962333","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":"Emerging Therapy in Osteoarthritis: Mesenchymal Stem Cells, Secretomes, and Using Hydrogels to Enhance Efficacy.","authors":"Qiming Pang, Jingdi Zhan, Zhuolin Chen, Lili Dong, Wei Huang","doi":"10.1007/s40259-025-00728-y","DOIUrl":"10.1007/s40259-025-00728-y","url":null,"abstract":"<p><p>Osteoarthritis is a prevalent condition among middle-aged and elderly populations characterized primarily by the progressive degeneration of articular cartilage. Despite advances in medical technology, the complexity of osteoarthritis pathogenesis presents significant challenges in halting or reversing cartilage degradation. Recently, mesenchymal stem cells and their secretome have emerged as promising regenerative therapies for osteoarthritis. Mesenchymal stem cells not only differentiate into chondrocytes to repair cartilage defects but also maintain chondrocyte homeostasis by interacting with existing chondrocytes and modulating synovial inflammation. Additionally, the proteins and bioactive molecules contained within the mesenchymal stem cell secretome offer multifaceted therapeutic benefits. However, challenges such as the limited survival and integration of transplanted mesenchymal stem cells, potential for unwanted differentiation, and variable efficacy of the secretome persist. Hydrogels, which mimic the chemical and mechanical properties of the extracellular matrix, are frequently utilized as carriers for mesenchymal stem cells and their secretome in osteoarthritis treatments. This review explores the current applications of mesenchymal stem cells and their secretome in osteoarthritis therapy, proposing innovative strategies to overcome these existing treatment limitations.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"555-571"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186456","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":"Switching from Adalimumab Reference Product to and Among Adalimumab Biosimilars Outside the USA: Insights for US Clinicians.","authors":"John R P Tesser, Aline Charabaty, Adelaide A Hebert","doi":"10.1007/s40259-025-00719-z","DOIUrl":"10.1007/s40259-025-00719-z","url":null,"abstract":"<p><p>Ten adalimumab biosimilars have been introduced in the United States (USA) since 2023, while adalimumab biosimilars have been available for several years in other countries. These experiences of biosimilar uptake outside the USA can inform US-based healthcare professionals on switching in real-life practice settings. Considerations include how healthcare professionals might meaningfully address patient concerns about outcomes to improve patient satisfaction. A search of the MEDLINE database was used to identify publications on switching to and among adalimumab biosimilars in an ex-US setting, with no restriction on publication language and using a time frame of 1 January 2017 through 12 December 2023, coinciding with the European Union approval of the first adalimumab biosimilar, adalimumab-atto, in March 2017. This narrative review aims to provide insights into the efficacy and safety of transitioning to and among adalimumab biosimilars in adult patients from clinical studies but also, more importantly, using real-world evidence (RWE) from outside the USA. Overall, RWE suggested that efficacy and outcomes were consistent in patients who underwent switching from the reference product (RP) across various immune-mediated inflammatory diseases when compared to patients who did not switch from the RP. The ex-US RWE of RP and biosimilar adalimumab switches generally reflected the experiences observed in clinical trials; however, RWE findings elucidated several challenges to biosimilar uptake, including patient education, provider training, and supportive policies.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"591-606"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957123","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":"Emerging Role of Targeted Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders.","authors":"Angela H Holian, Brian G Weinshenker","doi":"10.1007/s40259-025-00729-x","DOIUrl":"10.1007/s40259-025-00729-x","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease that results in recurring, often severe attacks on the optic nerves and spinal cord that may result in profound visual loss and paralysis. Since the late 1990s, NMOSD was treated with traditional immunosuppressive therapies. Recently, four monoclonal antibodies (mAbs) were granted Food and Drug Administration approval for aquaporin-4 antibody (AQP4-IgG)-seropositive NMOSD treatment: eculizumab, inebilizumab, satralizumab, and ravulizumab. These targeted immunomodulatory therapies have emerged as a transformative approach to effectively reduce NMOSD attack frequency in AQP4-IgG-seropositive patients. We explore the role of these preventative mAbs for NMOSD management by reviewing the efficacy, safety, mechanisms of action, and administration of these agents, and compare them to rituximab and traditional immunosuppressants. We discuss therapy selection and the clinical challenges of therapeutic management, including medication adherence, therapeutic monitoring strategies, economic considerations, and medication accessibility, while managing therapy failure and indications for transitioning to alternative therapies.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"573-589"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282256","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":"The Use of Biologics for Thyroid Eye Disease.","authors":"Shoaib Ugradar, Emanuil Parunakian, Raymond S Douglas","doi":"10.1007/s40259-025-00726-0","DOIUrl":"10.1007/s40259-025-00726-0","url":null,"abstract":"<p><p>Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease. It is an autoimmune disorder that may present with signs of inflammation and extracellular matrix modification, leading to the characteristic features of swelling within the orbit, proptosis, diplopia, and vision loss. Recently, a growing body of work has focused on novel therapies for the treatment of TED. We review novel therapeutic agents aimed at treating TED. A review of the literature was performed through search of PubMed, Scopus, and Web of Science databases for terms related to the treatment of TED. There are multiple therapeutic agents available for the treatment of TED, focusing on the different molecular pathways that are dysregulated in the pathogenesis of the condition. Therapeutic targets include: B cells (rituximab), cytokines (interleukin [IL]-6] and IL-11), insulin-like growth factor 1 receptor, and antibodies (neonatal fragment crystallizable receptor). Currently, clinical evidence supports the use of anti-insulin-like growth factor 1 receptor therapy. However, research involving anti-IL-11, anti-IL-6, and the neonatal fragment crystallizable receptor is promising.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"607-619"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233102","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":"Beyond Cost: Observations on Clinical and Patient Benefits of Biosimilars in Real-World Settings.","authors":"Tore K Kvien, Neil Betteridge, Ines Brückmann, Wolfram Bodenmüller, Galyna Bryn, Silvio Danese, João Gonçalves, Zorana Maravic, Carter Thorne, Laura Wingate, Paul Cornes","doi":"10.1007/s40259-025-00727-z","DOIUrl":"10.1007/s40259-025-00727-z","url":null,"abstract":"<p><p>The introduction of biosimilars into healthcare systems globally is recognized by many as a healthcare success. Despite this, questions have been raised about whether biosimilars can deliver sufficient value to patients and healthcare professionals, as well as sufficient cost saving, for their use in treatment to be worthwhile. In this review, we discuss how the increasing financial burden of complex therapeutic medicines, such as biologics, can be ameliorated by off-patent biosimilar medicines, particularly with increasing worldwide incidences of cancer and other chronic diseases. We then describe real-world cases that demonstrate the significant direct and indirect benefits of biosimilars to patients and healthcare systems beyond costs. Healthcare sustainability is crucial to ensuring that healthcare systems can continue to deliver high-quality care to patients. The savings realized from the introduction of biosimilars have expanded treatment options and improved access to therapies across a spectrum of diseases. Cost savings from biosimilar use have also led to changes in treatment guidelines, increasing the availability of biologic medicines for earlier lines of therapy. This expansion of access can have a positive impact on the overall patient experience and can reduce the overall disease burden. However, the adoption of biosimilars has not been universally successful, and faces challenges in the current healthcare landscape and in the pharmaceutical development pipeline.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"537-553"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233101","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}