Peripherally administered therapeutics for neurological indications are challenged with anatomical and physiological barriers that limit their ability to access their site of action in the central nervous system (CNS). This is particularly true for complex therapeutics such as antibodies, immunotherapeutics, and gene therapies. The blood–brain barrier is the specialized structure...
Background Only a minority of patients with advanced gastric cancer (GC) or esophagogastric junction (EGJ) adenocarcinoma derive durable benefit from anti-programmed cell death 1 (PD-1) therapy. However, reliable biomarkers for real-world clinical decision-making remain limited. Objective To identify tumor site-specific genomic alterations associated with outcomes of nivolumab...
Background Patients with immune-mediated inflammatory diseases are routinely transitioned from originator biologics to biosimilars to reduce healthcare costs. While barriers related to patient and practitioner beliefs and knowledge are well-documented, less focus has been placed on system-level factors that may hinder biosimilar uptake. Aims This review aims to identify system...
Engineered virus-like particles (eVLPs) have emerged as a promising class of delivery systems for genome editing agents. By combining the efficient cellular entry of viral vectors with the safety advantages of nonviral platforms, eVLPs enable transient delivery of ribonucleoproteins such as Cas9, base editors, and prime editors. Successive design strategies, from rational...
Atopic dermatitis is a chronic inflammatory skin disease affecting approximately 15–20% of children and 2–10% of adults worldwide. Epidermal barrier dysfunction and immune dysregulation are central to its pathogenesis, creating a self-perpetuating cycle in which barrier disruption exacerbates inflammation, which in turn further impairs skin barrier integrity. The OX40/OX40L axis...
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...
Background 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. Objective This phase III trial aimed to investigate the...
Background AVT05, a recombinant, human, immunoglobulin G1қ monoclonal antibody, is a biosimilar to Simponi®. Objectives 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...
Background Golimumab is a safe and effective treatment for patients with rheumatoid arthritis. Biosimilars to the reference product (RP; Simponi®) may make treatment more accessible. Objectives 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...
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...
Background Advanced therapy medicinal products (ATMPs) often require long-term monitoring to assess both safety and efficacy post-authorisation due to uncertainties identified during the approval process. This study aims to characterise the use of real-world data (RWD) in post-authorisation measures (PAMs) for ATMPs approved in the European Union. Methods A systematic extraction...
Background and Objective Denosumab is a fully human monoclonal antibody (IgG2) k subclass that targets and binds with high affinity and specificity to receptor activator of nuclear factor-κB ligand (RANKL). Gedeon Richter’s denosumab RGB-14-P and RGB-14-X are proposed biosimilar drug products to the reference medicinal products Prolia® and Xgeva® (marketing authorisation holder...
Background and Objective Tocilizumab is a recombinant, humanised monoclonal antibody of the immunoglobulin G1 (IgG1) subclass, which specifically targets the interleukin-6 receptor (IL-6R). The RGB-19 product was developed as a biosimilar to the reference medicinal product RoActemra® (authorised for use in the European Union [EU]). The current study focuses on the demonstration...
Since blinatumomab’s approval as the first bispecific antibody (BsAb) in cancer therapy, these immunomodulatory agents have achieved substantial success in lymphoid malignancies. A decade after provisional approval in relapsed settings, blinatumomab became part of first-line induction therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL). Now, six additional BsAbs...
Comparative immunogenicity is a key regulatory requirement for biosimilars. In a streamlined biosimilar development process, absent a comparative clinical efficacy study, the analytical data and clinical pharmacokinetics (PK) study need to provide sufficient evidence for a conclusion of comparable immunogenicity. In this case study, we have reviewed the role of analytical and...
Background Increasing therapeutic options for inflammatory bowel disease calls for tools to aid choice of sequencing. We investigated if pharmacokinetic (PK) and pharmacodynamic (PD) failure mechanisms prompting therapy change influenced subsequent outcomes when switching to a different biologic drug class. Methods Retrospective single-center cohort study including patients...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease that results in recurring, often severe attacks on the optic nerves and spinal cord that may result in profound visual loss and paralysis. Since the late 1990s, NMOSD was treated with traditional immunosuppressive therapies. Recently, four monoclonal antibodies (mAbs) were granted Food and Drug...
The introduction of biosimilars into healthcare systems globally is recognized by many as a healthcare success. Despite this, questions have been raised about whether biosimilars can deliver sufficient value to patients and healthcare professionals, as well as sufficient cost saving, for their use in treatment to be worthwhile. In this review, we discuss how the increasing...
Objective To evaluate the impact of demand- and supply-side policies on the biosimilar market penetration and identify effective strategies for promoting biosimilar uptake in eight high-income countries. Methods We analyzed biosimilar market penetration for infliximab, rituximab, and trastuzumab in six European countries—France, Germany, Italy, Spain, Sweden, and the UK—and two...
Background Promoting the use of biosimilars is a global issue from the perspective of reducing medical costs. In Japan, the replacement of original biopharmaceuticals with biosimilars has not progressed as expected. To promote the use of biosimilar monoclonal antibodies, it is necessary to increase the public’s understanding of biosimilars by evaluating and confirming the quality...
Fabry disease is a rare but life-threatening, X-linked, inherited lysosomal storage disorder in which globotriaosylceramide is insufficiently metabolized because of reduced α-galactosidase A activity. Cellular globotriaosylceramide accumulation causes a multisystemic disease, which, if left untreated, reduces life expectancy in female and male individuals by around 10 and 20...
Ten adalimumab biosimilars have been introduced in the United States (USA) since 2023, while adalimumab biosimilars have been available for several years in other countries. These experiences of biosimilar uptake outside the USA can inform US-based healthcare professionals on switching in real-life practice settings. Considerations include how healthcare professionals might...
Immunoglobulin M (IgM) antibodies are an essential and conserved part of adaptive immunity. IgMs assemble into pentamers and hexamers that bind to antigens with high avidity. Pentamers incorporate a small protein called J-chain (JC) that is important for their transcytosis via the poly-immunoglobulin receptor (pIgR). IgM antibodies can efficiently activate complement and interact...
Limited real-world data on biological drug use in older patients with immune-mediated inflammatory diseases (IMIDs) exist despite these drugs carrying serious risks in this population. We aimed to describe the frequency and persistence of biological drug use in older patients (≥ 65 years) with IMID, including inflammatory bowel diseases (IBDs), psoriatic arthritis/psoriasis...