Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
Background: The monkeypox virus (MPXV) has attracted considerable global attention due to its potential to cause widespread outbreaks, necessitating the development of rapid and accurate diagnostic methods of significant clinical importance. A29, a key envelope protein of MPXV, represents a promising diagnostic target. Methods: A novel monoclonal antibody, D10, was isolated from the human Tomlinson I+J phage display library by biopanning against the recombinant A29 protein. The D10 Fab fragment was expressed and purified, and its binding affinity was characterized by biolayer interferometry. Molecular docking was performed to predict potential interacting residues. Specificity and detection performance were evaluated by direct and competitive enzyme-linked immunosorbent assay (ELISA). Results: D10 possesses a unique complementarity-determining region sequence and exhibits strong binding affinity toward the A29 protein. Structural modeling analysis suggested potential interacting residues of A29, including Gln67, Arg74, Asn75, Arg81, and Asn84, which may primarily interact with Ser10, Thr5, Gly49, Gly47, and Glu97 in the heavy chain of D10. The binding affinity, determined by biolayer interferometry, showed a dissociation equilibrium constant of 6.44 nM, indicating strong binding capability. Furthermore, competitive ELISA demonstrated that D10 binds selectively to the A29 protein, with a half-maximal inhibitory concentration of 1.88 μg/mL and a limit of detection of 0.12 μg/mL. Conclusions: Overall, this monoclonal antibody provides a valuable tool for the immunological detection of MPXV and holds potential for future clinical diagnostic applications....
Background: Post-approval manufacturing changes for biologics require rigorous comparability assessments to ensure uninterrupted quality and clinical performance. CMAB007 (Aomaishu®), a China-approved (2023) omalizumab biosimilar, underwent process enhancements—including media optimization and anion-exchange chromatography substitution—yielding a 5-fold increase in production without altering the host cell line. Methods: A novel three-arm tiered strategy was adopted to compare post-change CMAB007, pre-change CMAB007, and reference (Xolair®) products. Critical quality attributes (CQAs) were classified into tiers based on risk impact, with tier-specific acceptance criteria. Comprehensive analytics assessed structure, post-translational modifications, purity/impurities, activity, and Fc-mediated functions. Forced degradation (lyophilized/reconstituted states) and accelerated stability studies were evaluated. Based on the high degree of CMC similarity and to prevent “biological drift”, the pharmacokinetic (PK) and safety comparability of the post-change CMAB007 versus the reference product (Xolair®) was confirmed in a randomized, double-blind, two-arm study in healthy males (N = 114; single 150 mg subcutaneous administration). The pre-change product was not included in this clinical PK study. Results: Post-change CMAB007 exhibited analytical similarity within tiered acceptance criteria for all CQAs. Stability studies confirmed enhanced robustness under stress conditions. PK equivalence was demonstrated for AUC0–inf (GMR: 99.82%; 90% CI: 91.46~108.94%), AUC0–t (99.54%; 91.40~108.41%), and Cmax (101.88%; 95.21~109.01%). Immunogenicity (ADA incidence: 10.5% vs. 12.5%, p = 0.742) and safety profiles were comparable. Conclusions: This study pioneers a tiered three-arm comparability strategy for post-approval changes, integrating advanced analytics, risk-based quality assessment, and clinical validation. The approach mitigates “biological drift” risks, ensuring biosimilar quality, efficacy, and safety while enabling sustainable production scalability....
Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies are widely used for chronic migraine prevention, but comparative real-world evidence on healthcare utilization remains limited. This study aimed to compare the association of onabotulinumtoxinA versus CGRP monoclonal antibodies with acute triptan prescription and migraine-related return visits in patients with chronic migraine. Methods: We conducted a retrospective cohort study using the TriNetX global federated electronic health record database from 2018 to 2024. Adults with chronic migraine who initiated onabotulinumtoxinA or a CGRP monoclonal antibody were matched 1:1 by propensity score. The primary outcomes were time to acute triptan prescription and time to first migraine-related return visit during follow-up. Results: After propensity score matching, 10,140 patients were included in each treatment group. OnabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies (hazard ratio 0.513, 95% confidence interval 0.481–0.546; p < 0.001), whereas migraine-related return visits were similar between groups (hazard ratio 1.008, 95% confidence interval 0.977–1.039; p = 0.69). Conclusions: In this multicenter real-world analysis, onabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies, while migraine-related return visits were comparable. These findings reflect treatment-related healthcare utilization patterns in routine practice and should be interpreted considering the limitations of retrospective electronic health record data....
N-glycosylation, particularly terminal mannose exposure, is a critical quality attribute affecting macrophage targeting and the clinical efficacy of enzyme replacement therapy for Gaucher disease. This study developed a universal, sensitive, and quantitative method to compare the N-glycan profiles of three recombinant human glucocerebrosidase products from different expression systems: imiglucerase, velaglucerase alfa, and velaglucerase beta. Using 2-aminobenzamide labeling combined with HILIC-UPLC-FLD and high-resolution mass spectrometry, an N-glycan profiling platform was established. A multidimensional calibration system integrating retention time, glucose unit values, and mass-to-charge ratios was constructed, and collision-induced dissociation tandem MS was used to identify isomers and phosphorylated glycans. The method showed good specificity, linearity, precision, and accuracy. Glycan profiling revealed clear product-dependent differences: imiglucerase was enriched in core-fucosylated Man3 structures, velaglucerase alfa was dominated by Man9 and contained more phosphorylated and sialylated glycans, whereas velaglucerase beta showed a highly homogeneous Man5 profile. These findings demonstrate how distinct manufacturing strategies shape glycosylation patterns and provide a basis for biosimilar development and comparability assessment....
Background The introduction of biosimilars can lead to substantial price reductions which can alter costeffectiveness conclusions in health technology assessments. This study, undertaken for the National Institute for Health and Care Excellence (NICE), aimed to pilot a test-and-learn approach for biosimilars appraisals whilst pragmatically assessing the cost-effectiveness of bevacizumab (originator and biosimilars) plus fluoropyrimidinebased chemotherapy versus chemotherapy alone for patients with metastatic colorectal cancer. Methods A partitioned survival model with three health states (progression-free, post-progression and dead) was used. No additional active lines of treatment were modelled assuming that all further treatments were costeffective and assuming no interaction between bevacizumab and the efficacy of subsequent treatments. Analyses were undertaken independently for the use of bevacizumab plus fluoropyrimidine-based chemotherapy as firstline, and second-line, treatment. Analyses were conducted in line with NICE guidance. The clinical effectiveness of treatments was estimated from reviews of previous NICE technology appraisals, published literature, and expert input. Confidential prices of bevacizumab weighted by the market share were used. Results The use of bevacizumab plus fluoropyrimidine-based chemotherapy was shown to extend life and increase quality-adjusted life-years (QALYs). Whilst cost per QALY values cannot be reported due to confidentiality reasons, the NICE Appraisal Committee stated that these were below what NICE considers a cost-effective use of resources for both first- and second-line treatment. Conclusions The pragmatic modelling approach piloted was accepted by NICE and allowed for a quicker, internally funded, appraisal of bevacizumab biosimilars; this approach likely can be extended to other biosimilar appraisals....
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