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We studied alpha-glucosidase activity in plasma and leukocytes after an infusion of 40 mg/kg of recombinant alglucosidase alpha in patients with classic infantile Pompe disease to assess the pharmacokinetics and identify potential surrogate efficacy markers of gene therapy in patients on enzyme replacement therapy. Samples were collected by pharmacokinetic curves (n = 5) and random samples (n = 21 patients). Alpha-glucosidase activity was measured in plasma (substrate 4-methylumbelliferyl-α-D-glucopyranoside, MU) and leukocytes (substrate glycogen, Gn, and MU). Plasma peak concentration occurred at the end of the infusion, reaching concentrations > 5000 and > 100,000 times higher than the control and untreated patient levels, with a median half-life of 3.1 h (1.3-4.2 h). In leukocytes, plasma peak concentration occurred 24 h after the start of enzyme replacement therapy; plasma peak concentration did not exceed the control level (0.7 [Gn] and 0.9 [MU] times higher than controls). The estimated half-life was 2-4 days. Seven days after enzyme replacement therapy, median enzyme activity was 1.3 times higher than the control levels in plasma and within the control range in leukocytes; after 14 days, median values in plasma and leukocytes were below the control level. These findings suggest alpha-glucosidase activity in plasma and leukocytes may serve as an efficacy marker for gene therapy studies in patients with classic infantile Pompe disease receiving enzyme replacement therapy. Similar studies with next-generation enzyme replacement therapy are advised.

Nanocarriers (NCs) are nanosized delivery systems that can be engineered from lipids, polymers, inorganic compounds, viral structural proteins and extracellular vesicles to transport cargo efficiently. Their unique characteristics, including biocompatibility, a modifiable surface for targeted delivery, increased uptake and sustained release of antigens, make them an ideal platform for vaccine development. NCs can also improve antigen stability, increase retention and act as adjuvants to enhance immune responses. Nanovaccines offer promising solutions to overcome the issues of conventional vaccine design in terms of efficacy, time and resource consumption. However, challenges in developing nanovaccines, such as a limited understanding of NC mechanisms of action, upscaling, safety and regulatory issues, need to be addressed to advance NCs into licensed vaccines. This review describes the types, advantages, limitations and clinical applications of NCs, with updates on nanovaccine candidates for infectious diseases and cancer in clinical trials, along with key lessons learnt. The development of nanovaccines that are protective against multiple pathogenic strains or for prophylactic treatment for cancer could potentially enhance global capacity in pandemic preparedness and disease prevention. Hence, continued research to advance NC technologies and to gain a deeper understanding of their mechanisms of immune activation is warranted to pave the way for more effective, personalized and accessible vaccines.

Even though the use of biosimilar medicines is increasing across European countries, detailed and regularly published official data on biosimilar uptake are not publicly available except in Italy and Portugal. The main objective of this study was to provide a nationwide assessment of biosimilar consumption and uptake patterns in Spain between 2016 and 2023. Data were provided by the Ministry of Health and included the defined daily dose (DDD) of biosimilars (N = 17) dispensed through both community pharmacies and public hospitals, biosimilar market share, and information on the registration status of both the bio-originator and biosimilars of each active principle. Data were analysed using non-parametric tests and bootstrap analysis with 10,000 replications, considering market share, time since market entry, number of competitors, and indication type (acute vs. chronic). The results show that biosimilar penetration increased from 9% in 2016 to 47% in 2023. In 2023, the biosimilar market share was substantially higher in the hospital setting (68%) compared to community pharmacies (34%). Biosimilars indicated for acute conditions achieved significantly higher market shares than those used for chronic conditions (p < 0.05). A positive correlation was observed between market share and the number of competitors, which was statistically significant only in the hospital setting (p = 0.007), while no significant association was found in the community pharmacy setting. Additionally, no correlation was identified between biosimilar market penetration and the time elapsed since the introduction of the first biosimilar. Other factors, such as prices, tendering, interchangeability, patients' characteristics, etc., may also influence biosimilar use. We suggest further analysis of policies aimed at promoting biosimilar adoption in Spain.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Advances in understanding MS immunopathogenesis have led to the development of monoclonal antibodies (MABs) that target key immune pathways, providing highly selective and effective treatment options. Approved MABs, including those against CD20, CD25, CD52, and α4‑integrin, have demonstrated robust efficacy in reducing relapse rates, suppressing MRI activity, and, to some extent, slowing disability progression. Meanwhile, emerging agents aim to modulate neuroinflammation, promote remyelination, and improve safety profiles. This review summarizes the mechanisms of action, clinical efficacy, safety, and future perspectives of MAB therapies in MS, highlighting lessons from discontinued agents and opportunities for next‑generation therapeutics.

Chronic obstructive pulmonary disease (COPD), a leading cause of global morbidity and mortality, is a complex and heterogeneous respiratory condition characterised by incompletely reversible airflow obstruction on spirometry. The aetiologies and pathological patterns of COPD are varied, which has long been viewed as a hindrance to targeted treatment. Yet inflammation is central to the diverse mechanisms of COPD pathogenesis, and type 2 inflammation has emerged as a measurable, modifiable and clinically meaningful therapeutic target in those patients in whom it is identified. The approval of first biological therapy against type 2 inflammation in COPD builds on our understanding of immunological mechanisms in airways diseases, is informed by a decade of randomised trials and makes possible a fundamental shift in our approach to this common condition. This review will (1) assess aspects of pathological inflammation in COPD, namely type 1, 2 and 3 inflammation, and the role of epithelial alarmins; (2) examine data from randomised trials on the efficacy and safety of monoclonal antibodies against inflammatory mediators in COPD; and (3) discuss future directions for biological therapies in COPD, including new patient populations, new agents and new approaches that focus on high-risk disease and open the door to prevention.

Drug-resistant bacteria have become one of the greatest threats to human health in recent decades. With the large-scale abuse of antibiotics, bacteria resistant to traditional antibiotics are becoming increasingly common while clinical options for treating refractory infections are rapidly diminishing. Antimicrobial peptides (AMPs) as a promising alternative to traditional antibiotics, exhibit unique antibacterial mechanisms and potent antimicrobial activity. In recent years, numerous AMPs have been identified and validated in laboratory settings for their efficacy against the 'ESKAPE' pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. Although the clinical translation of AMPs is currently hindered by challenges such as stability, toxicity, and production costs, advances in biotechnology and continued research are paving the way for their development as promising alternatives for treating drug-resistant ESKAPE pathogens. This review focuses on summarizing AMPs with demonstrated efficacy against ESKAPE pathogens and explores their clinical application potential, aiming to provide insights for future AMP research and therapeutic development.

Oncolytic viruses (OVs) are naturally occurring or genetically modified viruses that selectively target cancer cells for infection, replication, and lysis. Specifically, their tumor tropism and promising antitumoral efficacy through direct oncolysis and indirect immunogenic activation make OVs a novel immunotherapeutic class of high interest. OVs find particular relevance in solid tumors that are notoriously refractory to chemoradiation, are immunologically silent, express heterogeneous antigens, and are difficult to penetrate with existing agents. Distinct OVs have been identified; many have been extensively studied and have been approved or are pending approval in humans, including adenoviruses, herpes simplex viruses, reoviruses, vaccinia viruses, and measles viruses. While each virus type is unique in size, structure, targeting, replication, and behavior, they broadly share several antitumor mechanisms-direct oncolysis, immunogenic cell death, and modification of the tumor microenvironment. Modifications to OVs build on these features, ranging from genetic manipulation to insertion of cytokines or genes of interest, such as checkpoint inhibitors, altering virulence for tumor specificity or safety, to viral targeting enhancements. Moreover, the most recent iterations of OVs are often paired as combination therapies with chemotherapy, radiation, or other immunotherapeutic agents. This review aims to provide an up-to-date, in-depth discussion of major OVs, their precise mechanisms of action, modifications for improved therapeutic outcomes, and current combination therapy approaches against solid tumors in pre-clinical and clinical settings.