BioDrugs最新文献

筛选
英文 中文
Analytical Data and Single-Dose PK are Sufficient to Conclude Comparable Immunogenicity for Biosimilars: An Ustekinumab Case Study. 分析数据和单剂量PK足以得出类似生物仿制药的免疫原性结论:Ustekinumab案例研究
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-09-01 Epub Date: 2025-07-17 DOI: 10.1007/s40259-025-00733-1
Martin Schiestl, Nivedita Roy, Michael Trieb, Joseph P Park, Elena Guillen, Gillian Woollett, Elena Wolff-Holz
{"title":"Analytical Data and Single-Dose PK are Sufficient to Conclude Comparable Immunogenicity for Biosimilars: An Ustekinumab Case Study.","authors":"Martin Schiestl, Nivedita Roy, Michael Trieb, Joseph P Park, Elena Guillen, Gillian Woollett, Elena Wolff-Holz","doi":"10.1007/s40259-025-00733-1","DOIUrl":"10.1007/s40259-025-00733-1","url":null,"abstract":"<p><p>Comparative immunogenicity is a key regulatory requirement for biosimilars. In a streamlined biosimilar development process, absent a comparative clinical efficacy study, the analytical data and clinical pharmacokinetics (PK) study need to provide sufficient evidence for a conclusion of comparable immunogenicity. In this case study, we have reviewed the role of analytical and clinical data in the immunogenicity assessment of all currently available ustekinumab biosimilars and their reference product. Public information for European Medicines Agency-and US Food and Drug Administration-approved biosimilars reveal that the single-dose clinical PK studies were sensitive in detecting differences in terms of immunogenicity between the biosimilar and the reference product, a finding that was replicated in the comparative clinical efficacy studies. The rates for anti-drug antibodies and neutralizing antibodies were comparable albeit numerically lower for all biosimilars compared to their reference product, which correlates with lower levels of non-human glycans such as α-1,3 galactose known to be potentially relevant for immunogenicity. Our study demonstrates that the single-dose clinical PK studies were sensitive in confirming comparable immunogenicity of ustekinumab biosimilars with their reference product. The comparative clinical efficacy studies revealed no additional information. This finding adds on to the evidence that clinical PK and the comparative analytical assessment, specifically the comparison of quality attributes with potential immunogenic relevance, suffice for the evaluation of immunogenicity of biosimilars in general.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"769-776"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658337","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}
引用次数: 0
Comprehensive Physico-chemical and Functional Similarity Assessment Study of RGB-14-P and RGB-14-X Drug Products as Proposed Biosimilars to Denosumab Reference Products. RGB-14-P和RGB-14-X作为Denosumab参考产品生物类似药的综合理化和功能相似性评估研究
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1007/s40259-025-00738-w
Ágnes Szonja Garai, Dániel Hüse, Ádám Fizil, Zsolt Zólyomi, Gábor Lehoczki, Andrea Kis, Zsuzsanna Kálmán-Szekeres, Viktor Háda
{"title":"Comprehensive Physico-chemical and Functional Similarity Assessment Study of RGB-14-P and RGB-14-X Drug Products as Proposed Biosimilars to Denosumab Reference Products.","authors":"Ágnes Szonja Garai, Dániel Hüse, Ádám Fizil, Zsolt Zólyomi, Gábor Lehoczki, Andrea Kis, Zsuzsanna Kálmán-Szekeres, Viktor Háda","doi":"10.1007/s40259-025-00738-w","DOIUrl":"10.1007/s40259-025-00738-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Denosumab is a fully human monoclonal antibody (IgG2) k subclass that targets and binds with high affinity and specificity to receptor activator of nuclear factor-κB ligand (RANKL). Gedeon Richter's denosumab RGB-14-P and RGB-14-X are proposed biosimilar drug products to the reference medicinal products Prolia<sup>®</sup> and Xgeva<sup>®</sup> (marketing authorisation holder: Amgen Europe B.V. in the European Union [EU] and Amgen Inc. in USA, respectively). The present study demonstrates the structural, physico-chemical and functional similarity between RGB-14 and reference drug products marketed in the EU and US.</p><p><strong>Methods: </strong>Using an extensive, state-of-the-art analytical and functional panel of 38 methods ensured the comprehensive characterisation of the biosimilar and reference drug products. To assess biosimilarity, physico-chemical and biological functional tests were performed using multiple orthogonal techniques, in addition to the in-depth comparison of the primary and higher-order structures of the therapeutic proteins.</p><p><strong>Results: </strong>It has been demonstrated that the primary and higher order structures of RGB-14-P and RGB-14-X drug products are identical or highly similar to those of EU/US Prolia<sup>®</sup> and Xgeva<sup>®</sup>. The purity profiles of the biosimilar and reference products were similar. Only minor differences were observed in glycosylation patterns and charge variant profiles. A wide range of bioassays was used demonstrating similarity in terms of potency, ligand and receptor binding. Additionally, during comprehensive analysis of the reference product data as the function of expiry dates, shifts were revealed in certain quality parameters, although these did not impact the biological activity of the products.</p><p><strong>Conclusion: </strong>The extensive analytical and functional similarity assessment study provides robust evidence that the structure and function of RGB-14-P and RGB-14-X are highly similar to those of EU/US Prolia<sup>®</sup> and Xgeva<sup>®</sup>.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"697-724"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788212","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}
引用次数: 0
Individual Prescribing Incentives for Biosimilars in Selected European Countries and the USA: a Scoping Literature Review. 在选定的欧洲国家和美国生物仿制药的个人处方激励:范围文献综述。
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1007/s40259-025-00736-y
Félix Lobo, Isabel Río-Álvarez, Ángeles Flores
{"title":"Individual Prescribing Incentives for Biosimilars in Selected European Countries and the USA: a Scoping Literature Review.","authors":"Félix Lobo, Isabel Río-Álvarez, Ángeles Flores","doi":"10.1007/s40259-025-00736-y","DOIUrl":"10.1007/s40259-025-00736-y","url":null,"abstract":"<p><p>The uptake of biosimilar medicines in Europe and the USA remains highly variable and at times slow, despite the significant potential for cost savings for both patients and healthcare systems. One of the most recommended measures to address this issue is the use of prescribing incentives. On the basis of a well-defined concept of individual prescribing incentives, we conducted a scoping literature review aimed at exploring their role in promoting the uptake of biosimilars in six countries with advanced healthcare systems (the USA, Denmark, England, Italy, France and Germany), with a particular focus on gain-sharing initiatives. Online databases and other sources were used to identify papers published between 2010 and 2023, resulting in the selection of 47 publications. The results suggest that there are few real-world programmes that use provider incentives offered by health systems to encourage prescribing of biosimilars. However, we found gain-sharing schemes of particular interest in England, Italy, France and Germany, where savings are reinvested to improve the quality of care, incentivizing physicians and raising satisfaction, but without financial rewards. In contrast, we found unplanned disincentives hindering the uptake of biosimilars in the USA, as well as very successful top-down strategies that do not rely on individual incentives, including centralized procurement in Denmark, although it remains to be seen whether the success is idiosyncratic to its specific circumstances. In addition, the hypothesis that gain-sharing initiatives with the aforementioned characteristics are more adaptable to different cultural, organizational and political settings to promote biosimilar prescribing merits further research.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"777-791"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764439","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}
引用次数: 0
Comprehensive Physico-Chemical and Functional Similarity Assessment of Intravenous and Subcutaneous RGB-19 Drug Products as Proposed Biosimilars to Tocilizumab Reference Product. 静脉注射和皮下注射RGB-19药物作为托珠单抗参考产品生物类似药的综合理化和功能相似性评估
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1007/s40259-025-00734-0
Katalin Solti, Sarolta Timári, Tamás Faludi, Attila Iliás, Rózsa Hegedüs, Zoltán Pataj, Viktor Háda
{"title":"Comprehensive Physico-Chemical and Functional Similarity Assessment of Intravenous and Subcutaneous RGB-19 Drug Products as Proposed Biosimilars to Tocilizumab Reference Product.","authors":"Katalin Solti, Sarolta Timári, Tamás Faludi, Attila Iliás, Rózsa Hegedüs, Zoltán Pataj, Viktor Háda","doi":"10.1007/s40259-025-00734-0","DOIUrl":"10.1007/s40259-025-00734-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Tocilizumab is a recombinant, humanised monoclonal antibody of the immunoglobulin G1 (IgG1) subclass, which specifically targets the interleukin-6 receptor (IL-6R). The RGB-19 product was developed as a biosimilar to the reference medicinal product RoActemra<sup>®</sup> (authorised for use in the European Union [EU]). The current study focuses on the demonstration of structural, physico-chemical and functional similarity between RGB-19 (intravenous [IV] and subcutaneous [SC] presentations) and EU-sourced RoActemra<sup>®</sup> (IV and SC presentations).</p><p><strong>Methods: </strong>The RGB-19 biosimilar tocilizumab product was comprehensively tested using an extensive state-of-the-art analytical and functional panel of 44 methods to demonstrate similarity to the EU-sourced RoActemra<sup>®</sup>. Biosimilarity was rigorously evaluated through an extensive array of orthogonal physico-chemical and functional assays, supplemented by a detailed comparative characterisation of the primary and higher order structures of the therapeutic proteins.</p><p><strong>Results: </strong>Extensive structural analyses confirmed that the primary and higher order structures of tocilizumab proteins in RGB-19 IV and SC drug products are identical or exhibit a high degree of similarity to those of the RoActemra<sup>®</sup> reference products. The impurity profiles of RGB-19 and RoActemra<sup>®</sup> products were found to be highly comparable, as demonstrated by a series of physico-chemical techniques. A high level of similarity was shown for the most critical (soluble IL-6R binding and cell-based anti-proliferation assay) and for all other bioassay attributes. Based on the statistical evaluation, negligible differences could be detected for sialylation, glycation, fragments and charge variants, which do not affect the functional properties.</p><p><strong>Conclusion: </strong>Based on the similarity study, RGB-19 and RoActemra<sup>®</sup> can be considered highly similar drug products. The minor differences found for some physico-chemical attributes do not affect the biological potency, binding and other critical attributes, and are therefore not considered clinically meaningful.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"675-696"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764438","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}
引用次数: 0
Introduction of Biopharmaceuticals in Europe: A Cross-Sectional Study of Early Diffusion Patterns and Data Availability. 生物制药在欧洲的介绍:早期扩散模式和数据可用性的横断面研究。
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI: 10.1007/s40259-025-00732-2
Ivar Veszelei, Brian Godman, Katri Aaltonen, Gisbert W Selke, Kristina Garuolienė, Agnese Cangini, Amanj Kurdi, António Teixeira Rodrigues, Caridad Pontes, Carla Torre, Carlotta Lunghi, Edel Burton, Elita Poplavska, Freyja Jónsdóttir, Guenka Petrova, Irene Langner, Irina Iaru, Irina Odnoletkova, Juraj Slabý, Katarina Gvozdanović, Leena Saastamoinen, Ott Laius, Ria Benkö, Silvija Žiogaitė, Stuart McTaggart, Tanja Mueller, Thais de Pando, Tomáš Tesař, Zornitsa Mitkova, Björn Wettermark
{"title":"Introduction of Biopharmaceuticals in Europe: A Cross-Sectional Study of Early Diffusion Patterns and Data Availability.","authors":"Ivar Veszelei, Brian Godman, Katri Aaltonen, Gisbert W Selke, Kristina Garuolienė, Agnese Cangini, Amanj Kurdi, António Teixeira Rodrigues, Caridad Pontes, Carla Torre, Carlotta Lunghi, Edel Burton, Elita Poplavska, Freyja Jónsdóttir, Guenka Petrova, Irene Langner, Irina Iaru, Irina Odnoletkova, Juraj Slabý, Katarina Gvozdanović, Leena Saastamoinen, Ott Laius, Ria Benkö, Silvija Žiogaitė, Stuart McTaggart, Tanja Mueller, Thais de Pando, Tomáš Tesař, Zornitsa Mitkova, Björn Wettermark","doi":"10.1007/s40259-025-00732-2","DOIUrl":"10.1007/s40259-025-00732-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biopharmaceuticals add value in the treatment of many diseases but different health systems in Europe face clinical and economic challenges with introducing them. Joint efforts across Europe are therefore essential to ensure their sustainable and equitable use. However, to date few cross-national comparative studies have assessed their introduction. This study aimed to assess the availability of health authority data and variation in the early diffusion of biopharmaceuticals across Europe.</p><p><strong>Methods: </strong>A cross-sectional study was undertaken to analyze the diffusion of 17 biopharmaceuticals, approved between 2015 and 2019, among European countries between 2015 and 2022. The study assessed data availability, diffusion rates measured as accumulated defined daily doses per 1000 inhabitants, as well as relative rankings between countries during the first 4 years following market authorization.</p><p><strong>Results: </strong>Twenty countries and two regions out of 31 European countries provided data on biopharmaceutical utilization for out-of-hospital care, 15 provided wholesaler data, and 14 provided hospital data. Certain countries and regions contributed data in multiple categories, while six did not provide any data. Diffusion rates were assessed for 17 countries and two regions, which showed appreciable variation, with secukinumab and erenumab being introduced in most countries and follitropin delta and tildrakizumab in the least number of countries. Germany, Austria, and Norway demonstrated the highest early diffusion rates, while Lithuania, Romania, and Latvia had the lowest.</p><p><strong>Conclusions: </strong>This study revealed a substantial variation between European countries and regions in the early diffusion of biopharmaceuticals and the availability of data to monitor their use. The reasons behind these patterns require further investigation to support European countries in optimizing the use of biopharmaceuticals to reach an equitable and cost-effective use of medicines across Europe.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"735-751"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798108","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}
引用次数: 0
Real-World Data Included in Post-authorisation Measures: A Case Study of Approved Advanced Therapy Medicinal Products in the European Union between 2013 and 2024. 批准后措施中包含的真实世界数据:2013年至2024年欧盟批准的先进治疗药物案例研究
IF 6.9 2区 医学
BioDrugs Pub Date : 2025-08-26 DOI: 10.1007/s40259-025-00737-x
Diogo Almeida, Diana Mandslay, Peter G M Mol, Bruno Sepodes, Carla Torre
{"title":"Real-World Data Included in Post-authorisation Measures: A Case Study of Approved Advanced Therapy Medicinal Products in the European Union between 2013 and 2024.","authors":"Diogo Almeida, Diana Mandslay, Peter G M Mol, Bruno Sepodes, Carla Torre","doi":"10.1007/s40259-025-00737-x","DOIUrl":"https://doi.org/10.1007/s40259-025-00737-x","url":null,"abstract":"<p><strong>Background: </strong>Advanced therapy medicinal products (ATMPs) often require long-term monitoring to assess both safety and efficacy post-authorisation due to uncertainties identified during the approval process. This study aims to characterise the use of real-world data (RWD) in post-authorisation measures (PAMs) for ATMPs approved in the European Union.</p><p><strong>Methods: </strong>A systematic extraction of all PAMs from publicly available European Medicines Agency (EMA) regulatory documents for ATMPs approved between January 2013 and December 2024 was performed, followed by the identification of the presence and sources of RWD. Additional databases including the HMA-EMA Catalogue of RWD studies and sources and ClinicalTrials.gov were consulted.</p><p><strong>Results: </strong>Amongst 25 ATMPs approved by the European Commission over the study period, a total of 118 PAMs were identified, of which 49 (41.5%) involved RWD. Most RWD-PAMs were imposed by the EMA (n = 34; 69.4%), secondary data use was the most referenced data use type (n = 28; 57.1%) and registries were the main source of RWD being mentioned (n = 26; 53.1%). Further, 5 (10.2%) included a comparator group and 13 (32.5%) incorporated patient-reported outcomes.</p><p><strong>Conclusions: </strong>This study emphasises the instrumental role of RWD in the post-authorisation monitoring of ATMPs in the European Union. PAMs reflect the regulatory flexibility for these products, shifting some efforts to the post-authorisation phase to address benefit-risk gaps. Enhancing the use of RWD in this context could improve evidence generation, minimise uncertainties and support more informed regulatory decisions.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941686","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}
引用次数: 0
Author's Reply to Gonçalves: "Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review". 作者对gonalalves的回复:“聚乙二醇化蛋白治疗的不良影响:一项有针对性的文献综述”。
IF 5.4 2区 医学
BioDrugs Pub Date : 2025-07-01 Epub Date: 2025-06-17 DOI: 10.1007/s40259-025-00725-1
Chae Sung Lee
{"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}
引用次数: 0
Progress and Challenges in the Treatment of Fabry Disease. 法布里病治疗的进展与挑战。
IF 5.4 2区 医学
BioDrugs Pub Date : 2025-07-01 Epub Date: 2025-05-01 DOI: 10.1007/s40259-025-00723-3
Malte Lenders, Elise Raphaela Menke, Eva Brand
{"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}
引用次数: 0
Interrogation of Structure-Activity Relationships in Charge Variants of Therapeutic IgG2s Enabled by Free-Flow Isoelectric Focusing Fractionation. 自由流动等电聚焦分离诱导的治疗性IgG2s电荷变体的构效关系研究。
IF 5.4 2区 医学
BioDrugs Pub Date : 2025-07-01 Epub Date: 2025-04-22 DOI: 10.1007/s40259-025-00718-0
Lingyu Wang, Yajun Zeng, Wenyuan Gao, Pengcheng Shen, Ping Han, Zhongli Zhang
{"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 D<sub>99</sub>-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}
引用次数: 0
Demand- Versus Supply-Side Policies in Market Penetration of Biosimilars: Which is More Effective? 生物仿制药市场渗透的需求侧与供给侧政策:哪一个更有效?
IF 5.4 2区 医学
BioDrugs Pub Date : 2025-07-01 Epub Date: 2025-05-09 DOI: 10.1007/s40259-025-00721-5
Gyeongseon Shin, Heejin Han, Gyeyoung Choi, Donghwan Lee, SeungJin Bae
{"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<sub>s</sub> = 0.69, p < 0.001) and shorter time to reach the majority point (r<sub>s</sub> = - 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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信