BioDrugs最新文献

{"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}

{"title":"Comment on \"Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review\".","authors":"Joao Goncalves, Paolo Caliceti","doi":"10.1007/s40259-025-00724-2","DOIUrl":"10.1007/s40259-025-00724-2","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"669-671"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315867","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 Fomivirsen, Patisiran, and Givosiran Odyssey: How the Success Stories May Pave the Way for Future Clinical Translation of Nucleic Acid Drugs.","authors":"Mona Mansouri, Kimia Mansouri, Zahra Taheri, Samira Hossaini Alhashemi, Ali Dehshahri","doi":"10.1007/s40259-025-00711-7","DOIUrl":"10.1007/s40259-025-00711-7","url":null,"abstract":"<p><p>Over the past 25 years, the approval of several nucleic acid-based drugs by the US Food and Drug Administration (FDA) has marked a significant milestone, establishing nucleic acid drugs as a viable therapeutic modality. These groundbreaking discoveries are the result of some crucial points in the timeline of nucleic acid drug development. The inventions used in fomivirsen (Vitravene; Isis Pharmaceuticals) development paved the road for structural backbone modifications as well as nucleobase and sugar modifications. The approval of patisiran (Onpattro; Alnylam) demonstrated an effective and safe delivery system for small interfering RNA (siRNA), extending potential applications to other nucleic acids such as messenger RNA (mRNA). Givosiran (Givlaari; Alnylam) further revolutionized the field with a carrier-free, targeted platform, utilizing N-Acetylgalactosamine (GalNAc)-siRNA conjugates to enable efficient delivery, expanding therapeutic applications beyond rare genetic disorders to more common conditions such as hyperlipidemia and hypertension. In this review paper, we highlight the evolution of nucleic acid-based drug development, focusing on the pioneering agents fomivirsen, patisiran, and givosiran, and discuss the ongoing challenges in advancing these therapeutics and vaccines.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"359-371"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787738","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":"Biosimilar Policies and Their Impact on Market Penetration of Adalimumab, Etanercept and Infliximab: A Policy Synthesis and Descriptive Analysis in 13 OECD Countries.","authors":"Alexander C T Tam, Jasleen Badesha, Daphne P Guh, Nick Bansback, Kevin K Peter, Aidan Hollis, Paul Grootendorst, Sang-Cheol Bae, Aslam H Anis, Wei Zhang","doi":"10.1007/s40259-025-00709-1","DOIUrl":"10.1007/s40259-025-00709-1","url":null,"abstract":"<p><strong>Background: </strong>Different biosimilar-promoting policies have been implemented worldwide to improve biosimilar uptake and reduce expenditures on costly biologics.</p><p><strong>Objective: </strong>The aim was to review biosimilar-promoting policies in 13 countries, and examine biosimilar uptake and expenditure reduction for adalimumab, etanercept, and infliximab, among countries with different biosimilar-promoting policies.</p><p><strong>Methods: </strong>Quarterly IQVIA MIDAS sales data from 2012 to 2023 for the three originators and their biosimilars in 13 countries were used. Two countries for a given setting (retail or hospital) and originator were paired if they differed only on one specific policy. Biosimilar uptake and relative expenditure reduction were compared between pairs. Biosimilar uptake was calculated by dividing the sales volume of biosimilars by the total sales volume of biosimilars and their corresponding originator. Expenditure reduction was the difference between the actual expenditure in 2023 and the but-for-biosimilar expenditure (based on the price of the originator in the year before biosimilar launch).</p><p><strong>Results: </strong>Biosimilar uptake and relative expenditure reduction have grown over time across the three originators in all country-settings. We identified ten country-setting-anti-tumor necrosis factor (anti-TNF) pairs for three policies: tendering, price link, and quotas. All three policies appeared to facilitate greater biosimilar uptake, but this did not consistently translate to greater expenditure reductions. Tendering facilitated greater reductions in three out of four paired comparisons in the retail setting and zero of two comparisons in the hospital setting. Price link with low discount rates (- 20 to - 25% of originator price) and prescribing quotas facilitated greater reductions in one of three comparisons and zero of one comparison in the hospital setting, respectively.</p><p><strong>Conclusions: </strong>Procurement of biosimilars through tendering could potentially reduce spending on anti-TNFs in the retail setting, whereas price links at low discounts did not appear to help. The impact of prescribing quotas needs to be further investigated.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"461-476"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490654","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":"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":"427-444"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","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}