BioDrugs最新文献

{"title":"Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.","authors":"Wei Wang, Shengnan Zhang, Changlin Dou, Baihui Hu, Hongtao Song, Fan Qi, Yanyan Zhao, Xiaojing Li, Ming Zhou, Jinlian Xie, Kunhong Deng, Qian Wu, Ling Ye, Chang Cui, Li Liu, Jie Huang, Guoping Yang","doi":"10.1007/s40259-024-00679-w","DOIUrl":"10.1007/s40259-024-00679-w","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab (Opdivo^®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.</p><p><strong>Objectives: </strong>This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo^®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed.</p><p><strong>Patients and methods: </strong>A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3 mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC_0-∞, and the secondary pharmacokinetic endpoints included AUC_0-t and C_max. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%.</p><p><strong>Results: </strong>This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo^® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo^® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC_0-∞, AUC_0-t, and C_max of LY01015 to Opdivo^® were 94.49% (90.29-98.88%), 94.92% (88.73-101.54%), and 96.55% (93.32-99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00-125.00%. The safety and immunogenicity were also comparable between the two groups.</p><p><strong>Conclusions: </strong>LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles.</p><p><strong>Trial registration: </strong>This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"855-865"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341165","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":"Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.","authors":"Amberley D Stephens, Trevor Wilkinson","doi":"10.1007/s40259-024-00682-1","DOIUrl":"10.1007/s40259-024-00682-1","url":null,"abstract":"<p><p>Complex integral membrane proteins, which are embedded in the cell surface lipid bilayer by multiple transmembrane spanning polypeptides, encompass families of proteins that are important target classes for drug discovery. These protein families include G protein-coupled receptors, ion channels, transporters, enzymes, and adhesion molecules. The high specificity of monoclonal antibodies and the ability to engineer their properties offers a significant opportunity to selectively bind these target proteins, allowing direct modulation of pharmacology or enabling other mechanisms of action such as cell killing. Isolation of antibodies that bind these types of membrane proteins and exhibit the desired pharmacological function has, however, remained challenging due to technical issues in preparing membrane protein antigens suitable for enabling and driving antibody drug discovery strategies. In this article, we review progress and emerging themes in defining discovery strategies for a generation of antibodies that target these complex membrane protein antigens. We also comment on how this field may develop with the emerging implementation of computational techniques, artificial intelligence, and machine learning.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"769-794"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494659","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":"Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab.","authors":"Krzysztof Selmaj, Karsten Roth, Josef Höfler, Klaus Vitzithum, Rafał Derlacz, Oliver von Richter, Cyrill Hornuss, Johann Poetzl, Barry Singer, Laura Jacobs","doi":"10.1007/s40259-024-00671-4","DOIUrl":"10.1007/s40259-024-00671-4","url":null,"abstract":"<p><p>A biosimilar medicine is a successor to a reference ('originator'/'original-brand') biologic medicine brought to market once the patent and exclusive marketing rights for the reference have expired. Biosimilar natalizumab (PB006 [biosim-NTZ]; developed by Polpharma Biologics S.A. and marketed globally as Tyruko^®; Sandoz) has been developed as a successor to reference natalizumab (Tysabri^® [ref-NTZ]; Biogen) and is the first US Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biosimilar in neurology. As per the FDA and EMA indications for ref-NTZ, biosim-NTZ is approved to treat relapsing forms of multiple sclerosis (USA, EU) and Crohn's disease (USA only). Approval of biosim-NTZ was based on the 'totality of evidence', a comprehensive body of data collected during the development process, demonstrating similarity to its reference medicine. The foundational step of demonstrating structural and functional similarity between biosim-NTZ and ref-NTZ confirmed identical primary and indistinguishable higher order structures, as well as matching binding affinity to α4β1/α4β7 integrins. Following the confirmation of matching structure and function, pharmacokinetic/pharmacodynamic similarity of biosim-NTZ to ref-NTZ in healthy subjects was demonstrated, with no clinically meaningful differences identified in safety and immunogenicity. A comparative, double-blind, randomized study (Antelope) was also conducted in patients with relapsing-remitting multiple sclerosis and demonstrated matching efficacy, safety, and immunogenicity with no clinically meaningful differences between biosim-NTZ and ref-NTZ. This review presents the totality of evidence that confirmed the biosimilarity of biosimilar natalizumab to its reference medicine, which supported its approval by the FDA and the EMA. [Graphical plain language summary available].</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"755-767"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341155","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":"Biochemical Amenability in Fabry Patients Under Chaperone Therapy-How and When to Test?","authors":"Malte Lenders, Elise Raphaela Menke, Eva Brand","doi":"10.1007/s40259-024-00678-x","DOIUrl":"10.1007/s40259-024-00678-x","url":null,"abstract":"<p><strong>Aim: </strong>Current recommendations for Fabry disease include α-galactosidase A (AGAL) activity measurements to assess the biochemical response in migalastat-treated patients. Owing to contradictory data from laboratories, we aimed to analyze why AGAL activity measures from dried blood spots (DBS) often fail to detect migalastat-mediated enzymatic activity increases in treated patients.</p><p><strong>Methods: </strong>43 patients with 58 visits under migalastat were consecutively recruited. Enzymatic AGAL activities were measured from DBS and peripheral blood mononuclear cells (PBMCs). Migalastat concentrations in sera were determined using modified serum-mediated inhibition assays to assess C_max and serum half-life. Results were set in relation to the time of last migalastat intake and blood sampling to assess an optimal timepoint for AGAL activity measures.</p><p><strong>Results: </strong>DBS-based AGAL activity measurements of 21 (42.0%) amenable patients were below the limit of detection. Serum samples from migalastat-treated patients showed significant AGAL inhibition, depending on the time between migalastat intake and blood sampling (r² = 0.8140, p < 0.0001). Migalastat concentrations were determined in serum samples confirming a C_max at 3 h and a serum half-life of 4 h. At 24 h after intake, migalastat clearance was significantly associated with renal function (r² = 0.3135, p = 0.0102). Enzymatic AGAL activities were higher in samples from DBS and PBMCs 24 h after migalastat intake (both p < 0.05).</p><p><strong>Conclusion: </strong>The optimal time for enzymatic AGAL activity measurement in migalastat-treated patients appears to be 24 h after the last migalastat intake. Since migalastat is a competitive inhibitor of AGAL, enzymatic AGAL activity measurements should be better performed from PBMCs to reduce migalastat-mediated interferences.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"845-854"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341154","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":"Eblasakimab, an Anti-IL‑13Rα1 Antibody, Reduces Atopy-Associated Serum Biomarkers in Moderate‑to‑Severe Atopic Dermatitis.","authors":"Ferda Cevikbas, Alison Ward, Karen A Veverka","doi":"10.1007/s40259-024-00685-y","DOIUrl":"10.1007/s40259-024-00685-y","url":null,"abstract":"<p><strong>Introduction: </strong>Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD.</p><p><strong>Methods: </strong>A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed.</p><p><strong>Results: </strong>Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose.</p><p><strong>Conclusion: </strong>The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor.</p><p><strong>Trial registration number: </strong>NCT04090229.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"821-830"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457392","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":"Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review.","authors":"Chae Sung Lee, Yogesh Kulkarni, Vicki Pierre, Manish Maski, Christoph Wanner","doi":"10.1007/s40259-024-00684-z","DOIUrl":"10.1007/s40259-024-00684-z","url":null,"abstract":"<p><p>The beneficial effects of polyethylene glycol (PEG)-conjugated therapeutics, such as increased half-life, solubility, stability, and decreased immunogenicity, have been well described. There have been concerns, however, about adverse outcomes with their use, but understanding of those adverse outcomes is still relatively limited. The present study aimed to characterize adverse outcomes associated with PEGylation of protein-based therapeutics on immunogenicity, pharmacologic properties, and safety. A targeted review of English language articles published from 1990 to September 29, 2023, was conducted. Of the 29 studies included in this review, 18 reported adverse safety outcomes such as hematologic complications, hepatic toxicity, injection site reactions, arthralgia, nausea, infections, grade 3 or 4 adverse events (AEs), and AE-related discontinuations and dose modifications. Fifteen studies reported immunogenicity-related outcomes, such as the prevalence of pre-existing antibodies to PEG, treatment-emergent antibody response, and hypersensitivity reactions to PEGylated drugs. Seven studies reported pharmacological outcomes such as increased clearance and reduced activity in response to PEGylated drugs. This review aims to contribute to a balanced view of PEGylated therapies by summarizing the adverse outcomes or lack of benefit associated with PEGylated therapeutics reported in the literature. We identified several studies characterizing adverse outcomes, pharmacological effects, and immunogenicity associated with the use of PEGylated therapeutics. Our findings suggest that using PEGylated therapeutics may require careful monitoring for adverse safety outcomes, including screening and monitoring for pre-existing antibodies and those induced in response to PEGylated therapy, as well as monitoring and adjusting the dosing of PEGylated therapeutics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"795-819"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457391","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":"Patient Satisfaction and Experience with CT-P17 Following Transition from Reference Adalimumab or Another Adalimumab Biosimilar: Results from the Real-World YU-MATTER Study.","authors":"Guillaume Bouguen, Laure Gossec, Vered Abitbol, Eric Senbel, Guillaume Bonnaud, Xavier Roblin, Yoram Bouhnik, Stéphane Nancey, Nicolas Mathieu, Jérôme Filippi, Lucine Vuitton, Stéphane Nahon, Azeddine Dellal, Alice Denis, Lucile Foulley, Caroline Habauzit, Salim Benkhalifa, Hubert Marotte","doi":"10.1007/s40259-024-00681-2","DOIUrl":"10.1007/s40259-024-00681-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar.</p><p><strong>Patients and methods: </strong>This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, \"What is your global satisfaction with the CT-P17 injection?\", using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17.</p><p><strong>Results: </strong>The total analysis population included 232 patients (IBD 72.0%, CIRD 28.0%). Median patient age was 57.0 years (interquartile range [IQR] 46.0-63.0), 50.4% were men, and median disease duration was 9 years (IQR 5-16). Approximately half of the cohort (51.2%) switched to CT-P17 from an ADA-BioS (including 19.4% from an ADA-BioS with citrate) and half (48.7%) from R-ADA. The proportion of patients who were satisfied with treatment was stable between baseline (under previous treatment) and 3 months (under CT-P17). More patients reported increased satisfaction after switching to CT-P17 from an ADA-BioS (22.7% vs 8.0% when switching from R-ADA; p = 0.002), or from an ADA-BioS containing citrate (28.9% vs 12.3% when switching from a citrate-free ADA-BioS; p = 0.008). Independent prognostic factors for increased satisfaction were previous treatment with an ADA-BioS (odds ratio [OR] 2.88 [95% confidence interval 1.17-7.08]; p = 0.021) and pain at the injection site under previous treatment (OR 1.26 [1.08-1.47]; p = 0.004). Significantly fewer patients reported pain, redness, itching, and hematoma after 3 months of CT-P17 treatment versus baseline (p < 0.001).</p><p><strong>Conclusions: </strong>The majority of patients had stable or increased treatment satisfaction after switching from R-ADA or an ADA-BioS to CT-P17. In particular, switching to CT-P17 from a low-concentration ADA-BioS or an ADA-BioS containing citrate was associated with increased patient satisfaction. An improvement in overall tolerance with CT-P17 versus previous adalimumab treatment was also reported.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT05427942, registered June 22, 2022.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"867-878"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341164","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":"Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness.","authors":"Tomoka Mamori, Maki Tanioka, Kenji Takada, Hirofumi Hamano, Takahiro Tsukioki, Yuko Takahashi, Tsuguo Iwatani, Tadahiko Shien, Shinichi Toyooka","doi":"10.1007/s40259-024-00686-x","DOIUrl":"https://doi.org/10.1007/s40259-024-00686-x","url":null,"abstract":"<p><strong>Background: </strong>Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important.</p><p><strong>Objective: </strong>This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population.</p><p><strong>Methods: </strong>The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization's VigiBase, the global adverse event reporting database.</p><p><strong>Results: </strong>No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization's VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates.</p><p><strong>Conclusions: </strong>By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457393","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":"Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept","authors":"Benjamin Stump, Aaron B. Waxman","doi":"10.1007/s40259-024-00680-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00680-3","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is a rare and progressive disease that continues to remain highly morbid despite multiple advances in medical therapies. There remains a persistent and desperate need to identify novel methods of treating and, ideally, reversing the pathologic vasculopathy that results in PAH development and progression. Sotatercept is a first-in-class fusion protein that is believed to primarily inhibit activin signaling resulting in decreased cell proliferation and differentiation, though the exact mechanism remains uncertain. Here, we review the currently available PAH therapies, data highlighting the importance of transforming growth factor-β (TGF-β) superfamily signaling in the development of PAH, and the published and on-going clinical trials evaluating sotatercept in the treatment of PAH. We will also discuss preclinical data supporting the potential use of the fusion protein KER-012 in the inhibition of aberrant TGF-β superfamily signaling to ameliorate the obstructive vasculopathy of PAH.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"27 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262711","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":"Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure","authors":"Whitney C. Weber, Daniel N. Streblow, Lark L. Coffey","doi":"10.1007/s40259-024-00677-y","DOIUrl":"https://doi.org/10.1007/s40259-024-00677-y","url":null,"abstract":"<p>Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"30 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262712","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}