BioDrugs最新文献

{"title":"Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.","authors":"Torleif Tollefsrud Gjølberg, Simone Mester, Gaia Calamera, Jenny Skjermo Telstad, Inger Sandlie, Jan Terje Andersen","doi":"10.1007/s40259-025-00708-2","DOIUrl":"https://doi.org/10.1007/s40259-025-00708-2","url":null,"abstract":"<p><p>Autoimmune diseases are highly prevalent and affect people at all ages, women more often than men. The most prominent immunological manifestation is the production of antibodies directed against self-antigens. In many cases, these antibodies (Abs) drive the pathogenesis by attacking the body's own healthy cells, causing serious health problems that may be life threatening. Most autoantibodies are of the immunoglobulin G (IgG) isotype, which has a long plasma half-life and potent effector functions. Thus, there is a need for specific treatment options that rapidly eliminate these pathogenic IgG auto-Abs. In this review, we discuss how the neonatal Fc receptor (FcRn) acts as a regulator of the high levels of not only IgG Abs, but also albumin, by rescuing both these soluble proteins from cellular catabolism, and how a molecular and cellular understanding of this complex biology has spurred an intense interest in the development of FcRn-targeting strategies for the treatment of IgG-driven autoimmune diseases. We find that this emerging therapeutic class demonstrates efficacy within several autoimmune diseases with distinct pathophysiology. This offers hope for both new therapeutic avenues for highly prevalent diseases currently treated by other means, and rare diseases with no approved therapies to date. In addition, we elaborate on studies that have led to approval of the first FcRn antagonists, the clinical progress and structural design of molecules in the pipeline, their position in the overall therapeutic landscape of autoimmunity, the design of next-generation antagonists as well as the use of this receptor-targeting principle for other therapeutic applications.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742222","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":"Extracellular Vesicles and Immune Activation in Solid Organ Transplantation: The Impact of Immunosuppression.","authors":"Weicheng Xu, Karin Boer, Dennis A Hesselink, Carla C Baan","doi":"10.1007/s40259-025-00713-5","DOIUrl":"https://doi.org/10.1007/s40259-025-00713-5","url":null,"abstract":"<p><p>Recent advances in extracellular vesicle (EV) research in organ transplantation have highlighted the crucial role of donor-derived EVs in triggering alloimmune responses, ultimately contributing to transplant rejection. Following transplantation, EVs carrying donor major histocompatibility complex (MHC) molecules activate recipient antigen-presenting cells (APCs), initiating both alloreactive and regulatory T-cell responses. While immunosuppressive drugs are essential for preventing rejection, they may also influence the biogenesis and release of EVs from donor cells. This review examines the impact of maintenance immunosuppressive therapy on EV biogenesis and release post-transplantation. In addition, EV release and uptake may be influenced by specific factors such as the patient's end-stage organ disease and the transplant procedure itself. In-vitro studies using primary human parenchymal and immune cells-integrated with cutting-edge multi-omics techniques, including genomics, proteomics, lipidomics, and single-EV analysis-will offer deeper insights into EV biology and the mechanisms by which immunosuppressive agents regulate EV-initiated immune processes. A detailed understanding of how organ failure, the transplantation procedure and immunosuppressive drugs affect the biology of EVs may uncover new roles for EVs in immune activation and regulation in patients, ultimately leading to improved immunosuppressive strategies and better transplant outcomes.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717912","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":"Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.","authors":"Miaomiao Chen, Yuli Zhou, Kaicheng Bao, Siyu Chen, Guoqing Song, Siliang Wang","doi":"10.1007/s40259-025-00712-6","DOIUrl":"https://doi.org/10.1007/s40259-025-00712-6","url":null,"abstract":"<p><p>The development of immune checkpoint inhibitors has revolutionized the treatment of patients with cancer. Targeting the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1(PD-L1) interaction using monoclonal antibodies has emerged as a prominent focus in tumor therapy with rapid advancements. However, the efficacy of anti-PD-1/PD-L1 treatment is hindered by primary or acquired resistance, limiting the effectiveness of single-drug approaches. Moreover, combining PD-1/PD-L1 with other immune drugs, targeted therapies, or chemotherapy significantly enhances response rates while exacerbating adverse reactions. Multispecific antibodies, capable of binding to different epitopes, offer improved antitumor efficacy while reducing drug-related side effects, serving as a promising therapeutic approach in cancer treatment. Several bispecific antibodies (bsAbs) targeting PD-1/PD-L1 have received regulatory approval, and many more are currently in clinical development. Additionally, tri-specific antibodies (TsAbs) and tetra-specific antibodies (TetraMabs) are under development. This review comprehensively explores the fundamental structure, preclinical principles, clinical trial progress, and challenges associated with bsAbs targeting PD-1/PD-L1.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662024","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":"Interleukin-23 versus Interleukin-17 Inhibitors in Preventing Incidental Psoriatic Arthritis in Patients with Psoriasis: A Real-World Comparison From the TriNetX US Collaborative Network.","authors":"Sebastian Yu, An-Ping Huo, Yu-Hsun Wang, James Cheng-Chung Wei","doi":"10.1007/s40259-025-00705-5","DOIUrl":"10.1007/s40259-025-00705-5","url":null,"abstract":"<p><strong>Background: </strong>Psoriatic arthritis (PsA) is a common comorbidity in patients with psoriasis (PsO) that leads to significant disease burden. Biologic therapies targeting the interleukin (IL)-23/IL-17 axis have been widely used for PsO, but their comparative effectiveness in preventing PsA remains unclear.</p><p><strong>Objective: </strong>The study objective was to compare the occurrence of developing incidental PsA among PsO patients treated with interleukin-23 inhibitors (IL23is) or interleukin-17 inhibitors (IL17is).</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using real-world data from the TriNetX US Collaborative Network, including 53 healthcare organizations. Adult PsO patients treated with IL23is or IL17is between January 2019 and June 2022 were identified. Cox regression analysis was used to assess the risk of PsA incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Subgroup analyses were performed based on age, sex, and ethnicity. Sensitivity analyses included comparisons with tumor necrosis factor (TNF) inhibitors (TNFis) to ensure robustness.</p><p><strong>Results: </strong>A total of 4,580 PsO patients were included in the study, with 2,273 receiving IL23is and 2,307 receiving IL17is. Treatment with IL23is was associated with a significantly lower incidence of PsA compared to IL17is (HR = 0.60, 95% CI 0.44-0.82, P = 0.001). This reduction in risk was particularly notable in the 41- to 65-year age group (HR = 0.42, 95% CI 0.27-0.64, P < 0.001) and among females (HR = 0.57, 95% CI 0.38-0.86, P = 0.007). Subgroup analyses based on ethnicity revealed varying outcomes, with White patients showing a significant risk reduction (HR = 0.55, 95% CI 0.38-0.79, P = 0.001) but no significant risk reduction was observed in Black or African American patients (HR = 1.37, 95% CI 0.37-5.13, P = 0.637). Sensitivity analyses comparing IL23is and TNFis confirmed the robustness of the findings.</p><p><strong>Conclusion: </strong>IL23is are associated with a lower risk of PsA incidence compared to IL17is in PsO patients, particularly in specific age, sex, and ethnic groups. These findings suggest that IL23is may be more suitable for PsO patients at high risk of PsA and could inform potential updates to treatment guidelines. Further research should focus on refining therapeutic strategies by incorporating patient-specific factors such as comorbidities, ethnicity, and genetic predispositions, which could optimize biologic selection and enhance PsA prevention efforts in clinical practice.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"297-306"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057813","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":"Comparative Structure Activity Relationship Characterization of the Biosimilar BAT1806/BIIB800 to Reference Tocilizumab.","authors":"Yujie Liu, Jianhua Xie, Zhuxiang Li, Xiong Mei, Di Cao, Shengfeng Li, Linda Engle, Suli Liu, Hans C Ebbers, Cuihua Liu","doi":"10.1007/s40259-024-00698-7","DOIUrl":"10.1007/s40259-024-00698-7","url":null,"abstract":"<p><strong>Background: </strong>BAT1806/BIIB800 (Tofidence™/tocilizumab-bavi), a biosimilar of tocilizumab, demonstrated a high degree of analytical and functional similarity to reference tocilizumab (TCZ) in a comprehensive comparative analytical assessment. Minor differences with respect to TCZ were observed for some attributes and this study assessed the potential impact of these differences through structure activity relationship characterization.</p><p><strong>Methods: </strong>Structure activity relationship studies were conducted to assess glycation, glycosylation, charge variants, hydrophobicity, oxidation, and deamidation differences, using a range of investigative techniques. Structure activity relationship studies were performed on one lot each of BAT1806/BIIB800 and TCZ (European Union sourced only) except for glycation, where additional lots sourced from China and the USA were used.</p><p><strong>Results: </strong>Average total glycated protein content of BAT1806/BIIB800 was higher than TCZ (10.08% vs 1.19%); however, biological activity, including target binding and functional potency, was unaffected. Stress-induced glycation of BAT1806/BIIB800 and TCZ also did not affect the biological activity of the products despite up to 60% total glycation content. Minor differences were observed between BAT1806/BIIB800 and TCZ in glycosylation, charge variants, hydrophobicity, oxidation, and deamidation without a relevant impact on interleukin-6 receptor binding, Fc-receptor binding, and effector functions. In forced degradation studies, oxidation and deamidation trends were comparable between the two products.</p><p><strong>Conclusions: </strong>Comparative structure activity relationship characterization of BAT1806/BIIB800 and TCZ indicated that there are no relevant differences in quality attributes between BAT1806/BIIB800 and reference TCZ. Observed differences between BAT1806/BIIB800 and TCZ had no functional impact on BAT1806/BIIB800. The results support the conclusion that BAT1806/BIIB800 is similar to TCZ.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"307-320"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565900","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":"State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.","authors":"Julien Giron-Michel, Maël Padelli, Estelle Oberlin, Hind Guenou, Jean-Charles Duclos-Vallée","doi":"10.1007/s40259-024-00702-0","DOIUrl":"10.1007/s40259-024-00702-0","url":null,"abstract":"<p><p>Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment. These modifications enable CSCs to exhibit plasticity, differentiating into various resistant tumor cell types. Addressing this challenge requires urgent efforts to develop personalized treatments guided by biomarkers, with a specific focus on targeting CSCs. The lack of effective precision treatments for PLCs is partly due to the scarcity of ex vivo preclinical models that accurately capture the complexity of CSC-related tumors and can predict therapeutic responses. Fortunately, recent advancements in the establishment of patient-derived liver cancer cell lines and organoids have opened new avenues for precision medicine research. Notably, patient-derived organoid (PDO) cultures have demonstrated self-assembly and self-renewal capabilities, retaining essential characteristics of their respective in vivo tissues, including both inter- and intratumoral heterogeneities. The emergence of PDOs derived from PLCs serves as patient avatars, enabling preclinical investigations for patient stratification, screening of anticancer drugs, efficacy testing, and thereby advancing the field of precision medicine. This review offers a comprehensive summary of the advancements in constructing PLC-derived PDO models. Emphasis is placed on the role of CSCs, which not only contribute significantly to the establishment of PDO cultures but also faithfully capture tumor heterogeneity and the ensuing development of therapy resistance. The exploration of PDOs' benefits in personalized medicine research is undertaken, including a discussion of their limitations, particularly in terms of culture conditions, reproducibility, and scalability.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"237-260"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999412","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":"Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back.","authors":"Annapaola Mariniello, Maxime Borgeaud, Marc Weiner, Daniele Frisone, Floryane Kim, Alfredo Addeo","doi":"10.1007/s40259-024-00700-2","DOIUrl":"10.1007/s40259-024-00700-2","url":null,"abstract":"<p><p>Immunotherapy with checkpoint inhibitors has become the cornerstone of systemic treatment for non-oncogene addicted non-small-cell lung cancer. Despite its pivotal role, a significant proportion of patients-approximately 70-85%-either exhibit primary resistance to PD-1 blockade or develop acquired resistance following an initial benefit, even in combination with chemotherapy and/or anti-CTLA-4 agents. The phenomenon of primary and acquired resistance to immunotherapy represents a critical clinical challenge, largely based on our incomplete understanding of the mechanisms of action of immunotherapy, and the resulting lack of accurate predictive biomarkers. Here, we review the definitions and explore the proposed mechanisms of primary and acquired resistance, including those related to the tumor microenvironment, systemic factors, and intrinsic tumor characteristics. We also discuss translational data on adaptive changes within tumor cells and the immune infiltrate following exposure to checkpoint inhibitors. Lastly, we offer a comprehensive overview of current and emerging therapeutic strategies designed to prevent primary resistance and counteract acquired resistance.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"215-235"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424768","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":"Use of Semaglutide (Wegovy) in Adults in France: A Nationwide Drug Utilization Study.","authors":"Nadia Haddy, Hugo Jourdain, David Desplas, Marion Bertrand, Marie-Joelle Jabagi, Claire Rives-Lange, Mahmoud Zureik","doi":"10.1007/s40259-024-00699-6","DOIUrl":"10.1007/s40259-024-00699-6","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide 1 receptor agonists have shown promising results in obesity treatment. In France, semaglutide 2.4-mg (Wegovy) has benefited from an early-access program from July 2022 to September 2023.</p><p><strong>Objective: </strong>This study aimed to describe the user profile of semaglutide 2.4-mg and the dosage patterns under real-world conditions during this period.</p><p><strong>Methods: </strong>Between July 2022 and September 2023, semaglutide 2.4-mg initiators were identified through the nationwide APMO database (Accès Précoce-Médicaments Onéreux), built from the French National Health Data System (SNDS). The cohort was followed up until 31 December 2023. A sequence analysis was used to build clusters of dose escalation regimens.</p><p><strong>Results: </strong>Among the 6990 adult patients who started treatment, the median age was 49.0 years, with a majority of women (65.8%). The study revealed significant regional variations in initiation rates, with the highest in Ile-de-France (including Paris). Three groups of users were identified: standard adherence (74.5%), early discontinuation (13.0%), and high-dose initiation (12.5%). Factors influencing these clusters included age, with younger patients (25-34 years) more likely to discontinue early (odds ratio: 1.35 [95% confidence interval 1.05-1.75]). The use of anti-emetics during the first 5 months of the follow-up period was higher in the early-discontinuation group (15.7%) compared with the high-dose initiation group (9.0%) and standard adherence group (12.3%).</p><p><strong>Conclusions: </strong>This study involved a substantial number of real-life semaglutide 2.4-mg users and highlights the importance of monitoring treated patients from a public health perspective, given the broad prescription to come and the potential risks associated with misuse.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"321-332"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389900","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":"New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.","authors":"Lea Gerischer, Paolo Doksani, Sarah Hoffmann, Andreas Meisel","doi":"10.1007/s40259-024-00701-1","DOIUrl":"10.1007/s40259-024-00701-1","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a relevant proportion of patients does not achieve a satisfactory clinical improvement under standard treatment. Additionally, long-term therapy with steroids can cause significant side effects and latency to clinical improvement with standard steroid-sparing immunosuppressants and after thymectomy can take months to years. In recent years, treatment of MG has changed fundamentally due to improved evidence from phase 3 trials and the regulatory approval of complement inhibitors and FcRn inhibitors as add-on treatment options. This provides new optimism for substantially more patients reaching minimal manifestation status and has led to a shift in treatment strategy with more targeted therapies being employed early in the course of the disease, especially in patients with high disease activity. In this focussed review, we provide an overview of the diagnosis, classification and standard treatment of MG, followed by data from randomised controlled trials on the modern drugs already available for therapy and those still in the final stages of clinical development. In the second part, we provide an overview of real-world data for already approved therapies and outline how the availability of new biologicals is changing both clinical decision-making and patient journey.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"185-213"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045627","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":"An Automated Tool for Glycosimilarity Assessment of mAb Therapeutic Biosimilars: Trastuzumab and Bevacizumab as Case Studies.","authors":"Anuj Shrivastava, Sanjeet S Patil, Rohan Shah, Anurag S Rathore","doi":"10.1007/s40259-025-00704-6","DOIUrl":"10.1007/s40259-025-00704-6","url":null,"abstract":"<p><strong>Background: </strong>With the expiration of patents for multiple biotherapeutics, biosimilars are gaining traction globally as cost-effective alternatives to the original products. Glycosylation, a critical quality attribute, makes glycosimilarity assessment pivotal for biosimilar development. Given the complexity of glycoanalytical profiles, assessing glycosimilarity is nontrivial.</p><p><strong>Objective: </strong>This study proposes a Python-based automated tool for rapid estimation of glycosimilarity index (GI).</p><p><strong>Materials and methods: </strong>A comprehensive analytical glycosimilarity comparison of the trastuzumab originator product, Herclon (Roche), with five marketed biosimilars:Trasturel (Reliance Life Sciences), Canmab (Biocon), Vivitra (Zydus Ingenia), Hertraz (Mylan), and Biceltis (Cipla), has been performed. Similarly, a comparison between the bevacizumab originator product, Avastin (Roche), and its five biosimilars: Abevmy (Mylan), Krabeva (Biocon), Ivzumab (RPG LifeSciences), Bryxta (Zydus), and Advamab (Alkem Labs), is presented. Glycan profile  has been assessed using liquid chromatography-fluorescence detection, and the  data have been integrated using the XGBoost-machine learning algorithm to quantify glycan composition. The GI has been calculated by combining profile similarity and compositional similarity, estimated on the basis of the criticality and tolerance of each glycan.</p><p><strong>Results: </strong>The tool enabled rapid GI estimation (< 1 min/sample) with reduced errors compared with Excel (> 10 min/sample). Biosimilars exhibited high GI with several exceeding 95%, while the lowest GI observed were 87.80% for trastuzumab and 92.39% for bevacizumab.</p><p><strong>Conclusions: </strong>The Python-based tool offers a high-throughput and a reliable platform for glycosimilarity assessment, outperforming traditional analysis. Minor variations in glycosylation patterns were observed among the biosimilars, suggesting a modest glycosimilarity variation (GI range between 80 and 100%). However, the limited number of innovator batches analyzed constrained the establishment of definitive tolerance limits. Future studies should focus on analyzing larger datasets to improve accuracy and define precise tolerance limits, enhancing the tool's reliability and its potential to accelerate biosimilar development.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"333-345"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051516","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}