BioDrugs最新文献

{"title":"Phase I Studies of HLX26, A Novel Anti-LAG-3 Antibody, Monotherapy or Combination Therapy in Patients with Advanced Solid Tumors.","authors":"Rujiao Liu, Hui Jing, Yang Chen, Shuiping Gao, Jinghao Zhang, Xubo Cao, Ke Li, Yuanyuan Liu, Meng Meng, Cong Chen, Ci Sun, Haoyu Yu, Qingyu Wang, Jing Li, Yanmin Wu, Jian Zhang","doi":"10.1007/s40259-025-00751-z","DOIUrl":"10.1007/s40259-025-00751-z","url":null,"abstract":"<p><strong>Background: </strong>HLX26 is a novel, recombinant humanized anti-LAG-3 IgG4 monoclonal antibody that exhibits high affinity for LAG-3 and demonstrates that it can block LAG-3 and its ligand interaction and activate T cells in preclinical in vitro studies.</p><p><strong>Objective: </strong>These two phase I, dose-escalation studies evaluated the safety, tolerability, pharmacokinetics profile, and preliminary efficacy of HLX26 monotherapy, or in combination with serplulimab (PD-1 inhibitor), in patients with advanced/metastatic solid tumors or lymphomas.</p><p><strong>Patients and methods: </strong>Adult patients with advanced/metastatic solid tumors that have failed or deemed clinically unsuitable for standard therapy, or lymphoma received different doses of HLX26 alone (at 60, 150, 300, 500, and 800 mg administered every 3 weeks [Q3W]) in the HLX26-001 study, or HLX26 plus serplulimab (HLX26 at 500, 800, and 1600 mg plus serplulimab (300 mg) administered Q3W) in the HLX26-002 study, respectively. The primary end points for both studies were the dose-limiting toxicities (DLT) and maximum tolerable dose (MTD).</p><p><strong>Results: </strong>As of 18 August 2023, with a median follow-up duration of 12.8 months, 26 patients were screened for the HLX26-001 study, 18 of whom were enrolled. As of 31 August 2023, with a median follow up duration of 6.0 months, 14 patients were screened for the HLX26-002 study, 9 of whom received HLX26 plus serplulimab. No DLT was observed, and the MTD was not reached for both studies. In the HLX26-001 study, 17 (94.4%) patients experienced at least one treatment-emergent adverse event (TEAE), most commonly proteinuria (n = 6, 33.3%) and hypercholesterolemia (n = 5, 27.8%). In the HLX26-002 study, all nine (100.0%) patients experienced TEAEs that were all treatment-related and predominantly mild in severity.</p><p><strong>Conclusions: </strong>HLX26 was well-tolerated and safe at various doses as a single agent, and in combination with serplulimab for patients with advanced solid tumors and warrants further investigation.</p><p><strong>Trial registration: </strong>HLX26-001-ClinicalTrials.gov: NCT05078593; HLX26-002-ClinicalTrials.gov: NCT05400265.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"335-348"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984337","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":"Immunogenicity of Gene and Cell Therapies.","authors":"Kirk Hofman, Priyanka Jangied, Sathy V Balu-Iyer","doi":"10.1007/s40259-025-00756-8","DOIUrl":"10.1007/s40259-025-00756-8","url":null,"abstract":"<p><p>Gene and cell therapies have been gaining popularity with market approvals by the US Food and Drug Administration, European Medicines Agency, and other regulatory bodies. Adeno-associated viral vector gene therapies approved for rare inherited diseases and chimeric antigen receptor T-cell therapies approved as a novel modality for hematological anti-cancer therapies have led the way in a new paradigm of drug discovery and development. Previously incurable diseases such as hemophilia A and B have now been effectively treated via adeno-associated viral vector-mediated gene therapy, and chimeric antigen receptor T-cell therapies have provided cures for lymphomas in patients refractory to all previous treatments demonstrating the great promise of these agents. Immunogenicity is a major factor hampering the efficacy and eligible population of gene therapies as well as creates a safety risk for some individuals. Inherent attributes of adeno-associated viral vector gene and autologous chimeric antigen receptor T-cell therapies present a unique set of factors that can influence immunogenicity to the drug compared to widely used small-molecule or biologic drugs. This review outlines immunogenicity concerns of gene and cell therapy, and their clinical manifestations. We detail mechanisms by which these therapies can trigger innate, humoral, and cellular immunity. Additionally, we give an in-depth discussion of in silico, in vitro, and in vivo immunogenicity screening methods that have been applied in gene and cell therapy development, and the utility of each.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"215-236"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948571","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":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40259-025-00763-9","DOIUrl":"https://doi.org/10.1007/s40259-025-00763-9","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910343","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":"Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.","authors":"Namyeong Kim, Inchan Kwon","doi":"10.1007/s40259-025-00752-y","DOIUrl":"10.1007/s40259-025-00752-y","url":null,"abstract":"<p><p>Conditionally activatable antibodies represent a promising strategy to improve the therapeutic index of antibody-based drugs by restricting their activity to disease sites, thereby minimizing systemic toxicity. These engineered platforms leverage disease-associated cues-such as protease activity, pH, redox gradients, or other microenvironmental factors-to modulate antigen binding or effector function in a spatially and temporally controlled manner. In this review, we categorize recent advances in activatable antibody technologies into three principal strategies: (1) masking domains or peptides that block target recognition until removed by disease-specific triggers, (2) structural rearrangement by fusing external domains to antibodies to regulate access to the paratope, and (3) payload activation approaches in antibody-drug conjugates. We summarize key design principles, representative examples, and their preclinical or clinical development status, highlighting strengths, limitations, and translational challenges. Special attention is given to linker chemistry, trigger specificity, and pharmacokinetic considerations that influence therapeutic performance. Finally, we discuss emerging trends, including multi-input activation systems and integration with next-generation modalities such as bispecific antibodies and immune cell engagers, which could further refine target selectivity and broaden therapeutic applications. This overview highlights representative advances to guide the rational design of future activatable antibody platforms and to accelerate their progression toward clinical use.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"79-108"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773389","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":"Cell Engineering for Increasing Production of Recombinant Proteins in Mammalian Cells.","authors":"Xi Zhang, Yuan Shen, Zihan Guo, Yanfang Wang, Xiaoyin Wang, Tianyun Wang","doi":"10.1007/s40259-025-00753-x","DOIUrl":"10.1007/s40259-025-00753-x","url":null,"abstract":"<p><p>Mammalian cell lines are the preferred host cells for the biopharmaceutical industry. Chinese hamster ovary (CHO) and human embryonic kidney 293 (HEK293) cells are frequently utilized in the production of recombinant therapeutic proteins (RTPs) owing to their capacity to facilitate appropriate protein folding and perform accurate post-translational modifications (PTMs). However, there are still some bottlenecks in the biopharmaceutical process using mammalian cells, including lower productivity, higher production cost and increased risk of contamination compared with bacterial or yeast expression systems. In addition to vector, media and bioprocess optimization, advances in host cell engineering including gene overexpression, knockout and knockdown have significantly advanced cell-line development. Besides targeting known genes and pathways, miRNA engineering and omics analysis are also employed to enhance mammalian cell culture performance. Optimization of cell engineering and production processes further drives the development of more efficient mammalian cell expression systems. This review systematically summarizes key achievements in cell engineering and offers insights into potential targets and pathways for improving therapeutic protein production in mammalian cells.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"23-40"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556371","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":"Clinical Qualification of Subcutaneous Injection Devices for Monoclonal Antibodies.","authors":"Beate Bittner, Javier Munoz, Sabine Frank, Michael Dolton, Renato Ravanello, Markus Dembowski, Aude Clement, Wolfgang F Richter","doi":"10.1007/s40259-025-00755-9","DOIUrl":"10.1007/s40259-025-00755-9","url":null,"abstract":"<p><p>Subcutaneous autoinjectors serve as a convenient and user-friendly alternative to manual injection using prefilled syringes or handheld syringes, enhancing self-administration in decentralized care settings, patient compliance, and dosing accuracy. Autoinjectors consistently penetrate the skin to the same depth, and are, thus, expected to reduce variability in injection conditions as compared to more operator-dependent manual self-injection. Even with an established autoinjector platform, molecule-specific technical development requirements often preclude the availability of the automated device at the start of pivotal clinical studies. This necessitates manual injections during these studies and frequently subsequent pharmacokinetic comparability studies to transition to the autoinjector. A proposed Molecule-Independent Device Bridging Approach (MIDBA) aims to eliminate the need for dedicated pharmacokinetic comparability studies for each new monoclonal antibody developed with a previously validated autoinjector platform by referring to PK data from other mAbs with dosing volumes up to 2 mL. The rationale for this approach lies in the slow absorption rates of mAbs following SC injection, which is primarily influenced by the residence time in subcutaneous tissue and subsequent lymphatic drainage rather than the specifics of the injection method. A narrative review of clinical data from 29 pharmacokinetic comparability studies revealed that independent of the molecule and the injection device, comparable pharmacokinetic and tolerability profiles were achieved following manual and automated injection. The review supports the applicability of the MIDBA as a streamlined development pathway for autoinjector validation without molecule-specific pharmacokinetic studies. This framework is expected to present a novel methodology for efficient transition from manual to automated subcutaneous injections for biotherapeutics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"5-21"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145539086","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":"Xeligekimab, an Interleukin-17A Antagonist for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 48-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Shangzhu Zhang, Dong Xu, Shengyun Liu, Shujie Li, Xiaoxia Wang, Fenghong Yuan, Wei Gou, Baijie Xu, Lingyun Sun, Jieruo Gu, Dongmei Zhou, Xiaomei Li, Ning Kong, Yi Zhao, Jie Hao, Tianwang Li, Xiaoyun Fan, Qiang Shu, Hua Wei, Tao Jiang, Jing Yang, Long Qian, Hongsheng Sun, Xiaoyan Cai, Zhenyu Jiang, Guohua Yuan, Li Qin, Min Yang, Jian Xu, Wenqiang Fan, Li Sun, Hua Zhang, Chunyan Zhang, Ning Zhang, Zhanyun Da, Jiankang Hu, Jingchun Jin, Ju Liu, Lie Dai, Lingli Dong, Wei Wang, Xiaofeng Zeng","doi":"10.1007/s40259-025-00750-0","DOIUrl":"10.1007/s40259-025-00750-0","url":null,"abstract":"<p><strong>Background: </strong>Xeligekimab is a novel immunoglobulin G4 (IgG4) monoclonal antibody targeting interleukin-17A (IL-17A). In a phase III trial in patients with plaque psoriasis, xeligekimab showed efficacy and safety consistent with other IL-17A inhibitors, supporting its potential application in the treatment of spondyloarthritis.</p><p><strong>Objective: </strong>This phase III trial aimed to investigate the efficacy and safety of xeligekimab in patients with radiographic axial spondyloarthritis (r-axSpA).</p><p><strong>Methods: </strong>This was a phase III study conducted at multiple centers in China. Eligible patients were randomly assigned (1:1:1) to receive xeligekimab 100 mg, xeligekimab 200 mg, or placebo. Randomization was stratified by medication history (biologic-experienced vs. biologic-naïve) and weight (≥ 70 kg vs. < 70 kg). The primary endpoint was the proportion of patients achieving an Assessment of SpondyloArthritis International Society 20 (ASAS20) response at week 16. A key secondary endpoint was the ASAS40 response rate at the same time point.</p><p><strong>Results: </strong>A total of 465 patients were recruited. A significantly higher proportion of patients receiving xeligekimab 200 mg (n = 114 (74.0%); p < 0.001, 95% confidence interval (CI) 28.5-48.4) and xeligekimab 100 mg (n = 102 (65.8%); p < 0.001, 95% CI 19.4-41.0) achieved an ASAS20 response compared to the placebo group (n = 56 (35.9%)) at week 16. Similarly, a significantly higher ASAS40 response rate was observed in the xeligekimab 100 mg group (n = 62 (40.0%); p < 0.001) and the xeligekimab 200 mg group (n = 64 (41.6%); p < 0.001) compared to placebo. Adverse events were similar across all groups, with serious adverse events occurring in 1.6% of the treatment group during the core treatment period. No unexpected safety signals were reported through week 48.</p><p><strong>Conclusion: </strong>Xeligekimab demonstrated significant efficacy in improving the signs and symptoms of active r-axSpA in Chinese patients at week 16, with sustained effects observed through week 48 and no new safety signals identified.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT05881785 (Date: 21 May 2023).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"151-162"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145539058","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":"Pharmacokinetic Similarity of Biosimiliar AVT05 Versus Reference Product Golimumab in Healthy Adults: A Double-Blind, Three-Arm, Parallel-Group Study.","authors":"Chris Wynne, Ulrike Lorch, Edrich Krantz, Rohit Katial, Thomas Ashdown, Monica Luque, Abid Sattar, Masna Rai, Laxmikant Vashishta, Katarina Petrovic, Ruth Ruffieux, Steffen Leutz, Fausto Berti","doi":"10.1007/s40259-025-00749-7","DOIUrl":"10.1007/s40259-025-00749-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;AVT05, a recombinant, human, immunoglobulin G1қ monoclonal antibody, is a biosimilar to Simponi&lt;sup&gt;®&lt;/sup&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The purpose of this study was to investigate the pharmacokinetic (PK) similarity, safety, tolerability, and immunogenicity between AVT05 and US-licensed and European Union (EU)-approved reference product (RP) golimumab (US-RP and EU-RP, respectively) in healthy adult participants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Three hundred and thirty-six healthy male and female participants aged 18-55 years were randomized in a 1:1:1 ratio to AVT05, US-RP, or EU-RP. Participants received a single 50 mg/0.5 mL subcutaneous injection on Day 1 and were followed until Day 75. The primary PK endpoints were maximum serum concentration (C&lt;sub&gt;max&lt;/sub&gt;) and area under the serum concentration-time curve from time zero to infinity (AUC&lt;sub&gt;0-inf&lt;/sub&gt;). Pharmacokinetic similarity was demonstrated if the 90% confidence intervals for the geometric mean ratio for both AUC&lt;sub&gt;0-inf&lt;/sub&gt; and C&lt;sub&gt;max&lt;/sub&gt; were entirely contained within the prespecified margins of 80.00% and 125.00% for all six pairwise treatment comparisons. Secondary endpoints were additional PK parameters (area under the concentration-time curve from time zero to the last quantifiable concentration, time to C&lt;sub&gt;max&lt;/sub&gt;, terminal elimination rate constant, terminal elimination half-life, apparent volume of distribution, and apparent clearance), safety, tolerability, and immunogenicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Demographic and baseline characteristics were balanced between the treatment groups. The 90% confidence intervals for the geometric means ratio for the protein-adjusted primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C&lt;sub&gt;max&lt;/sub&gt; [AVT05/US-RP 89.45, 106.75; AVT05/EU-RP 92.33, 110.15; EU-RP/US-RP 88.64, 105.92]; AUC&lt;sub&gt;0-inf&lt;/sub&gt; [AVT05/US-RP 94.35, 108.40; AVT05/EU-RP 98.46, 113.13; EU-RP/US-RP 89.36, 102.76]), supporting the demonstration of PK similarity. The secondary PK parameters were also comparable between the treatment arms. The mean serum golimumab concentrations through Day 75 post-dose were similar between treatment arms. Overall, 66.1% of participants experienced at least one treatment-emergent adverse event (TEAE) during the study period. The frequency of TEAEs was comparable across the treatment arms. The majority of TEAEs were mild to moderate in severity. There were two serious TEAEs reported (one [0.9%] each in AVT05 and EU-RP arms), neither of which was considered treatment related. Local administration site reactions were mild in severity and observed in 6.1%, 10.8%, and 5.5% of participants in the AVT05, EU-RP, and US-RP arms, respectively. Overall, 87 (75.7%), 92 (82.9%), and 89 (80.9%) participants in the AVT05, EU-RP, and US-RP arms, respectively, were anti-drug antibody positive; among those 66 (57.4%), 68 (61.3%), and 61 (55.5%) pa","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"121-133"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480723","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":"Recombinant Molecules as a New Frontier in Mucositis Therapy.","authors":"Luís Cláudio Lima de Jesus, Rhayane Cristina Viegas Santos, Vasco Azevedo","doi":"10.1007/s40259-025-00758-6","DOIUrl":"10.1007/s40259-025-00758-6","url":null,"abstract":"<p><p>Mucositis significantly impairs patients' quality of life, and despite its clinical importance and the availability of symptomatic treatments, no gold-standard therapeutic protocol has been established. Recent advances in biotechnology and molecular biology have enabled the development of genetically engineered probiotic strains capable of producing or delivering therapeutic molecules directly to inflamed mucosal sites. Although several recombinant biotherapeutic bacteria have advanced to clinical evaluation, most have not yet reproduced the efficacy observed in preclinical models, and no products have yet been commercially approved for human use. This is the first review to comprehensively outline the recombinant molecules as an innovative biotherapeutic option for mucosal inflammation induced by chemoradiotherapy. In this review, we describe how genetically modified bacteria function as living drug delivery platforms, focusing on their ability to produce or deliver recombinant molecules, including antimicrobial peptides, antioxidant enzymes, growth factors, and interleukin receptor antagonists, for mucositis therapy. We further discuss key limitations, including biosafety, control of gene expression, and gut protection levels, while outlining future challenges.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"41-55"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653285","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":"Efficacy and Safety of Biosimilar AVT05 Versus Reference Product Golimumab in Combination with Methotrexate in Moderate-to-Severe Rheumatoid Arthritis: 52-Week Results of a Randomized, Parallel-Group, Double-Blind Study.","authors":"Monica Luque, Kristina Zhelyazkova, Laxmikant Vashishta, Masna Rai, Abid Sattar, Katarina Petrovic, Richard Bucknall, Steffen Leutz, Fausto Berti","doi":"10.1007/s40259-025-00748-8","DOIUrl":"10.1007/s40259-025-00748-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Golimumab is a safe and effective treatment for patients with rheumatoid arthritis. Biosimilars to the reference product (RP; Simponi&lt;sup&gt;®&lt;/sup&gt;) may make treatment more accessible.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study was to assess the efficacy of AVT05, a golimumab biosimilar, and RP, each used in combination with methotrexate, in participants with moderate-to-severe rheumatoid arthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a 52-week, randomized, double-blind, two-arm, parallel-group, active-controlled study. Participants were randomized 1:1 to receive AVT05 (n = 251) or RP (n = 251), 50 mg subcutaneously once every 4 weeks to Week 12 inclusive. Randomization was stratified by the baseline Disease Activity Score-28 for Rheumatoid Arthritis using C-Reactive Protein (DAS28-CRP) [≤ 5.1 and &gt; 5.1]. The primary endpoint was the change from baseline in DAS28-CRP at Week 16. At Week 16, responder participants (DAS28-CRP decreased by &gt; 0.6 from baseline and disease activity DAS28-CRP ≤ 5.1) initially enrolled in the AVT05 arm continued to receive AVT05 every 4 weeks. Responder participants initially randomized to RP were re-randomized 1:1 to either continue receiving RP or switch to AVT05. Non-responders were discontinued from the study drug. Change from baseline in DAS28-CRP response criteria at weeks 4, 8, 12, 24, 32, 40, 48, and 52 and percentage of subjects achieving American College of Rheumatology 20/50/70 at weeks 4, 8, 12, 16, 24, 32, 40, 48, and 52 were assessed as secondary endpoints. Safety and immunogenicity endpoints were also assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At Week 16, the least squares mean (standard error) change from baseline in DAS28-CRP in AVT05 and RP was - 2.89 (0.058) and - 2.98 (0.058), respectively. The two-sided 95% confidence interval of the least squares mean difference (0.09; standard error 0.082) was entirely contained within the prespecified equivalence margin of - 0.6, 0.6 (- 0.07, 0.25), supporting a demonstration of comparative efficacy. Two sensitivity analyses (one [S1] without exclusion of any data because of intercurrent events, and one [S2] excluding data following intercurrent events or relevant protocol deviations) supported the robustness of the primary endpoint estimates (S1 95% confidence interval - 0.07, 0.25; S2 95% confidence interval - 0.07, 0.25). There were no notable differences in subgroup analyses. Secondary efficacy analyses were consistent with the primary endpoint, including in participants who switched treatments. Overall safety profiles showed no clinically meaningful differences between treatments, including in participants who switched treatments. Immunogenicity profiles were comparable between treatment arms at all timepoints, including in participants who switched treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Analysis of the change in DAS28-CRP from baseline to Week 16 supported the assessment of comparative efficacy betwee","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"135-149"},"PeriodicalIF":6.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437062","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}