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Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study. Ixekizumab治疗中国患者活动性放射性轴性脊柱炎:一项III期、随机、双盲、安慰剂对照研究的16周和52周结果。
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-09-22 DOI: 10.1007/s40259-023-00625-2
Yu Xue, Jiankang Hu, Dongzhou Liu, Jingyang Li, Huaxiang Wu, Chunyu Tan, Lie Dai, Lingyun Sun, Zhijun Li, Zhengyu Xiao, Cibo Huang, Yan Yan, Fei Ji, Rong Chen, Hejian Zou
{"title":"Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Yu Xue, Jiankang Hu, Dongzhou Liu, Jingyang Li, Huaxiang Wu, Chunyu Tan, Lie Dai, Lingyun Sun, Zhijun Li, Zhengyu Xiao, Cibo Huang, Yan Yan, Fei Ji, Rong Chen, Hejian Zou","doi":"10.1007/s40259-023-00625-2","DOIUrl":"10.1007/s40259-023-00625-2","url":null,"abstract":"<p><strong>Introduction: </strong>Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA.</p><p><strong>Methods: </strong>Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16.</p><p><strong>Results: </strong>In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest.</p><p><strong>Conclusions: </strong>IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov identifier: NCT04285229.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"145-156"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111097","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
Effect of feeding frequency on reproductive performances and stress responses in gestating sows. 饲喂频率对妊娠母猪繁殖性能和应激反应的影响
IF 2.3 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2024-01-31 DOI: 10.5187/jast.2023.e42
Sung-Woong Jung, Sungho Do, Jae-Cheol Jang, Jinsu Hong, Geonil Lee, Yoo Yong Kim
{"title":"Effect of feeding frequency on reproductive performances and stress responses in gestating sows.","authors":"Sung-Woong Jung, Sungho Do, Jae-Cheol Jang, Jinsu Hong, Geonil Lee, Yoo Yong Kim","doi":"10.5187/jast.2023.e42","DOIUrl":"10.5187/jast.2023.e42","url":null,"abstract":"<p><p>The objective of this study was to investigate the influence of feeding frequency on a sow's reproductive performance and stress response during gestation. A total of twenty multiparous sows (Yorkshire × Landrace) were used in a completely randomized design based on their parity, body weight (BW), and backfat thickness (BFT), and the sows were allotted to two different feeding systems: 1) once daily feeding (OF) and 2) twice daily feeding (TF) in corn-soybean meal based diets. The gestation diet was formulated to contain 3,265 kcal of metabolizable energy (ME) / kg, 12.90% of crude protein (CP), and 0.75 % of total lysine. The lactation diet was formulated to contain 3,265 kcal of ME / kg, 16.80% of CP, and 1.08% of total lysine and provided ad libitum during lactation. In gestation, sow BFT and BF changes were not affected by feeding frequency, but higher BW and BW gain from day 35 to 90 and day 35 to 110 were observed in OF sow (<i>p</i> < 0.10). In lactation, feeding frequency did not influence on BW, BW gain, BFT, BF changes, average daily feed intake, and wean-to-estrus interval. Also, there were no differences in litter size, litter weight and piglet weight in lactating sows. OF sows had higher (<i>p</i> < 0.05; <i>p</i> < 0.10) protein, solid-not-fat, and total solid concentrations in colostrum compared to TF sows, while OF sows had a lower (<i>p</i> < 0.05) lactose concentration in colostrum compared to TF sows. Sows in OF showed significantly lower average daily water consumption (ADWC) from day 35 to 110 of gestation (<i>p</i> < 0.05). While there were no significant differences in stereotypic behaviors and salivary cortisol levels during gestation between treatments, the OF sows showed less time spending on the activity at day 105 (<i>p</i> < 0.05). In conclusion, reduced feeding frequency increased BW gain during gestation, decreased activation time, and changed the colostrum composition. This information may contribute to the understanding of the physiological and behavioral change of gestating sows by manipulating feeding frequency.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"8 1","pages":"135-144"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11007455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90074939","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
Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned? 靶向IL-6或IL-6受体治疗类风湿关节炎:我们学到了什么?
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-11-21 DOI: 10.1007/s40259-023-00634-1
Ali Berkant Avci, Eugen Feist, Gerd R Burmester
{"title":"Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned?","authors":"Ali Berkant Avci, Eugen Feist, Gerd R Burmester","doi":"10.1007/s40259-023-00634-1","DOIUrl":"10.1007/s40259-023-00634-1","url":null,"abstract":"<p><p>The use of different pathways in the treatment of rheumatoid arthritis has led to a significant decrease in the number of treatment-resistant patients. In this context, interleukin (IL)-6 inhibition has filled an important gap in rheumatoid arthritis treatment with its effectiveness and safety in both monotherapy and combinations. The process of IL-6 inhibition initiated with IL-6 receptor blockers has prompted questions regarding the potential impact and safety of different inhibitions of this pathway, such as the direct blockade of IL-6. Following the termination of the development of sirukumab because of mortality data in early studies, the investigation of olokizumab, which targets a different region of the IL-6 cytokine, has renewed the hope in this area and the safety concerns have been largely alleviated by the open-label extension data. In addition, the efficacy and safety of tocilizumab and sarilumab have led to a rapid investigation of biosimilars and new potent IL-6 receptor blockers. A comprehensive understanding of mechanisms of this pathway with further long-term clinical data and basic research may provide a decisive impact on selecting the appropriate mechanism as the first choice in personalized treatments.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"61-71"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290260","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
Immunotherapy Guided by Immunohistochemistry PD-L1 Testing for Patients with NSCLC: A Microsimulation Model-Based Effectiveness and Cost-Effectiveness Analysis. 免疫组织化学PD-L1检测指导的NSCLC患者免疫治疗:基于微刺激模型的有效性和成本效益分析。
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-10-04 DOI: 10.1007/s40259-023-00628-z
Mingjun Rui, Yingcheng Wang, Yunfei Li, Zhengyang Fei
{"title":"Immunotherapy Guided by Immunohistochemistry PD-L1 Testing for Patients with NSCLC: A Microsimulation Model-Based Effectiveness and Cost-Effectiveness Analysis.","authors":"Mingjun Rui, Yingcheng Wang, Yunfei Li, Zhengyang Fei","doi":"10.1007/s40259-023-00628-z","DOIUrl":"10.1007/s40259-023-00628-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;On the basis of immunohistochemistry PD-L1 testing results, patients with advanced non-small cell lung cancer (NSCLC) are treated differently. Theoretically, patients with high PD-L1 expression (50% or 1%) should receive PD-1 monotherapy for fewer adverse reactions and cost savings from avoiding chemotherapy; however, there is controversy surrounding the cut-off criteria (1% or 50%) for immunohistochemistry testing and threshold for PD-1 monotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to predict the effectiveness and cost-effectiveness of different immunotherapy strategies for patients with NSCLC in China from the healthcare system perspective.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and methods: &lt;/strong&gt;A microsimulation model was developed to evaluate the effectiveness and cost-effectiveness of three treatment strategies: PD-L1 testing (1%) (PD-1 monotherapy for those with PD-L1 expression at 1% threshold, and combination with chemotherapy for others with immunohistochemistry testing), PD-L1 testing (50%) (PD-1 monotherapy for those with PD-L1 expression at 50% threshold, and combination with chemotherapy for others with immunohistochemistry testing), and No PD-L1 testing (PD-1 combined with chemotherapy without immunohistochemistry testing). The model assumed 1000 patients per strategy, with each patient entering a unique clinical path prior to receiving treatment on the basis of PD-L1 test results. Clinical inputs were derived from clinical trials. Cost and utility parameters were obtained from the database and literature. One-way probabilistic sensitivity analyses (PSA) and six scenario analyses were used to test the model's robustness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study revealed a hierarchy of survival benefits across three strategies, with No PD-L1 testing demonstrating the most survival advantage, followed by PD-L1 testing (50%), and finally, PD-L1 testing (1%). The comparative analysis demonstrated that No PD-L1 testing significantly enhanced overall survival (OS) (HR 0.85, 95% CI 0.78-0.93), progression-free survival (HR 0.82, 95% CI 0.75-0.90), and progression-free2 survival (PFS2) (HR 0.91, 95% CI 0.83-0.99) when juxtaposed against PD-L1 testing (1%). However, these improvements were not as pronounced when compared with PD-L1 testing (50%), particularly in relation to PFS, PFS2, and OS. The cost-effectiveness analysis further unveiled incremental cost-utility ratios (ICUR), with No PD-L1 testing versus PD-L1 testing (50%) at $34,003 per quality-adjusted life year (QALY) and No PD-L1 testing versus PD-L1 testing (1%) at $34,804 per QALY. In parallel, the ICUR for PD-L1 testing (50%) versus PD-L1 testing (1%) stood at $35,713 per QALY. Remarkably, the PSA result under a willingness-to-pay (WTP) threshold of $10,144 per QALY, with a 100% probability, demonstrated PD-L1 testing (1%) as the most cost-effective option.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The survival benefits of PD-1 monotherapy for hig","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"157-170"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105058","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
AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies. 基于aav的视网膜和脉络膜血管疾病治疗策略:年龄相关性黄斑变性和糖尿病视网膜病变治疗的进展。
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-10-25 DOI: 10.1007/s40259-023-00629-y
Brenda F M Castro, Jason C Steel, Christopher J Layton
{"title":"AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.","authors":"Brenda F M Castro, Jason C Steel, Christopher J Layton","doi":"10.1007/s40259-023-00629-y","DOIUrl":"10.1007/s40259-023-00629-y","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"73-93"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50156873","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
Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review. 肌营养不良和肌营养不良的治疗Duchenne肌营养不良方法:比较综述。
IF 5.4 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-11-02 DOI: 10.1007/s40259-023-00632-3
Sylwia Szwec, Zuzanna Kapłucha, Jeffrey S Chamberlain, Patryk Konieczny
{"title":"Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.","authors":"Sylwia Szwec, Zuzanna Kapłucha, Jeffrey S Chamberlain, Patryk Konieczny","doi":"10.1007/s40259-023-00632-3","DOIUrl":"10.1007/s40259-023-00632-3","url":null,"abstract":"<p><p>Duchenne muscular dystrophy is a devastating disease that leads to progressive muscle loss and premature death. While medical management focuses mostly on symptomatic treatment, decades of research have resulted in first therapeutics able to restore the affected reading frame of dystrophin transcripts or induce synthesis of a truncated dystrophin protein from a vector, with other strategies based on gene therapy and cell signaling in preclinical or clinical development. Nevertheless, recent reports show that potentially therapeutic dystrophins can be immunogenic in patients. This raises the question of whether a dystrophin paralog, utrophin, could be a more suitable therapeutic protein. Here, we compare dystrophin and utrophin amino acid sequences and structures, combining published data with our extended in silico analyses. We then discuss these results in the context of therapeutic approaches for Duchenne muscular dystrophy. Specifically, we focus on strategies based on delivery of micro-dystrophin and micro-utrophin genes with recombinant adeno-associated viral vectors, exon skipping of the mutated dystrophin pre-mRNAs, reading through termination codons with small molecules that mask premature stop codons, dystrophin gene repair by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated genetic engineering, and increasing utrophin levels. Our analyses highlight the importance of various dystrophin and utrophin domains in Duchenne muscular dystrophy treatment, providing insights into designing novel therapeutic compounds with improved efficacy and decreased immunoreactivity. While the necessary actin and β-dystroglycan binding sites are present in both proteins, important functional distinctions can be identified in these domains and some other parts of truncated dystrophins might need redesigning due to their potentially immunogenic qualities. Alternatively, therapies based on utrophins might provide a safer and more effective approach.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"95-119"},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420466","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
Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access. 推进生物治疗的皮下给药方案:加快市场准入的临床策略。
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-10-13 DOI: 10.1007/s40259-023-00626-1
Beate Bittner, Johannes Schmidt
{"title":"Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access.","authors":"Beate Bittner, Johannes Schmidt","doi":"10.1007/s40259-023-00626-1","DOIUrl":"10.1007/s40259-023-00626-1","url":null,"abstract":"<p><p>In recent years, subcutaneous administration of biotherapeutics has made significant progress. The self-administration market for rheumatoid arthritis has witnessed the introduction of additional follow-on biologics, while the first subcutaneous dosing options for monoclonal antibodies have become available for multiple sclerosis. Oncology has also seen advancements with the authorization of high-volume subcutaneous formulations, facilitated by the development of high-concentration formulations and innovative delivery systems. Regulatory and Health Technology Assessment bodies increasingly consider preference data in filing dossiers, particularly in evaluating novel drug delivery methods. The adoption of a pharmacokinetic-based clinical bridging approach has become standard for transitioning from intravenous to subcutaneous administration. Non-inferiority studies with pharmacokinetics as the only primary endpoint have started deviating from traditional randomization schemes, favoring the subcutaneous route and comparing with historical intravenous data. While nonclinical and computational models made progress in predicting safety and immunogenicity for subcutaneously dosed antibodies, clinical trial evidence remains essential due to inter-individual variations and the impact of formulation parameters on anti-drug antibody formation. Ongoing technological advancements and the expanding knowledge base on pharmacokinetic-pharmacodynamic correlation across specialty areas are expected to further accelerate clinical development of subcutaneous biologics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"23-46"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190468","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
Outer Membrane Vesicle Vaccine Platforms. 外膜囊泡疫苗平台。
IF 6.8 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-10-05 DOI: 10.1007/s40259-023-00627-0
Francesca Micoli, Roberto Adamo, Usman Nakakana
{"title":"Outer Membrane Vesicle Vaccine Platforms.","authors":"Francesca Micoli, Roberto Adamo, Usman Nakakana","doi":"10.1007/s40259-023-00627-0","DOIUrl":"10.1007/s40259-023-00627-0","url":null,"abstract":"<p><p>Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development. There are a few licensed OMV vaccines mainly for the prevention of meningitis caused by Neisseria meningitidis serogroup B (MenB) and Haemophilus influenzae type b (Hib). There are several candidates in clinical development against other gram-negative organisms from which the OMVs are derived, but also against heterologous targets in which the OMVs are used as carriers (e.g. coronavirus disease 2019 [COVID-19]). The use of OMVs for targets other than those from which they are derived is a major advancement in OMV technology, improving its versatility by being able to deliver protein or polysaccharide antigens. Other advances include the range of genetic modifications that can be made to improve their safety, reduce reactogenicity, and increase immunogenicity and protective efficacy. However, significant challenges remain, such as identification of general tools for high-content surface expression of heterologous proteins on the OMV surface. Here, we outline the progress of OMV vaccines to date, particularly discussing licensed OMV-based vaccines and candidates in clinical development. Recent trends in preclinical research are described, mainly focused on genetic manipulation and chemical conjugation for the use of OMVs as carriers for heterologous protein and polysaccharide antigens. Remaining challenges with the use of OMVs and directions for future research are also discussed.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"47-59"},"PeriodicalIF":6.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41098871","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: 1
Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer's Disease. 抗淀粉样蛋白单克隆抗体治疗阿尔茨海默病
IF 5.4 2区 医学
BioDrugs Pub Date : 2024-01-01 Epub Date: 2023-11-13 DOI: 10.1007/s40259-023-00633-2
Jeffrey Cummings, Amanda M Leisgang Osse, Davis Cammann, Jayde Powell, Jingchun Chen
{"title":"Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer's Disease.","authors":"Jeffrey Cummings, Amanda M Leisgang Osse, Davis Cammann, Jayde Powell, Jingchun Chen","doi":"10.1007/s40259-023-00633-2","DOIUrl":"10.1007/s40259-023-00633-2","url":null,"abstract":"<p><p>Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's disease patients who have proven β-amyloid pathology (Aβ). One of these, lecanemab, has subsequently received full approval and other monoclonal antibodies are poised for positive review and approval. Anti-amyloid mAbs share the feature of producing a marked reduction in total brain Aβ revealed by amyloid positron emission tomography. Trials associated with slowing of cognitive decline have achieved a reduction in measurable plaque Aβ in the range of 15-25 centiloids; trials of agents that did not reach this threshold were not associated with cognitive benefit. mAbs have differences in terms of titration schedules, MRI monitoring schedules for amyloid-related imaging abnormalities (ARIA), and continuing versus interrupted therapy. The approximate 30% slowing of decline observed with mAbs is clinically meaningful in terms of extended cognitive integrity and delay of onset of the more severe dementia phases of Alzheimer's disease. Approval of these agents initiates a new era in Alzheimer's disease therapeutics with disease-modifying properties. Further advances are needed, i.e. greater efficacy, improved safety, enhanced convenience, and better understanding of ill-understood observations such as brain volume loss.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"5-22"},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716810","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
Acknowledgement to Referees. 鸣谢裁判员。
IF 6.8 2区 医学
BioDrugs Pub Date : 2023-12-18 DOI: 10.1007/s40259-023-00638-x
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