Expert Opinion on Biological Therapy最新文献

Introduction: The approval in 2011 of belimumab, the first biologic approved for systemic lupus erythematosus (SLE), paved the way for testing additional biologic agents to expand treatment options for SLE. We discuss new biologic therapies that show promising results and discuss some of the barriers that must be considered in SLE clinical trials.

Areas covered: This review focuses on established and novel biologics targeting the BAFF/APRIL, type-I IFN, CD20, and CD40/CD40 ligand pathways and on CAR-T therapy. We review the relevant clinical trials, focusing on safety and efficacy. A literature search was conducted in PubMed/MEDLINE. Keywords used were "Lupus Erythematosus, Systemic' OR (("Lupus* AND ("Biological Products' OR Biologics*)). These search results were filtered to include only clinical trials. In addition, literature from the authors' personal collections were considered.

Expert opinion: Several novel therapies have shown promising results. The treatment approach for SLE is shifting toward a balanced and targeted immunosuppression tailored to key drivers of SLE pathophysiology and diverse phenotypes. Given the number of agents already or soon-to-be approved, the appropriate therapy for a given patient must be a shared patient-physician decision.

Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an ultra-rare disease that arises from malignant precursor dendritic cells. Historically, there was no uniform standard-of-care chemotherapy. In this setting, outcomes were substandard, especially for patients not eligible for intensive chemotherapy, clinical trials, and/or hematopoietic stem cell transplantation, which constituted the majority of patients. The development of targeted therapy, namely the anti-CD123 agent tagraxofusp, marked the beginning of a new era in the treatment of BPDCN.

Areas covered: This review summarizes current targeted therapies in BPDCN, highlights recent therapeutic strategies and emerging approaches with the potential to improve patient outcomes. We also discuss key barriers to clinical implementation, including adverse events associated with anti-CD123-directed therapies and limitations related to treatment cost and accessibility.

Expert opinion: The approval of tagraxofusp established a foundation for targeted therapy in BPDCN and demonstrated high response rates, leading to the development of additional antibody - drug conjugates and cellular therapies targeting CD123. Other promising investigational targeted approaches may include BCL2 inhibitors, proteasome inhibitors, and therapies directed against surface antigens such as CD38 and CD303, as well as bromodomain and extraterminal (BET) inhibitors. Collectively, these strategies represent important advances that may significantly improve the historically poor outcomes associated with BPDCN.

Background: Axial spondyloarthritis (axSpA) leads to significant impairments in quality of life (QoL) and work productivity. While infliximab is effective in treating axSpA, its impact in patients with concomitant extra-skeletal manifestations is limited, particularly in the Greek population.

Aims: To evaluate intravenous infliximab's impact on disease activity, QoL, and work productivity in Greek patients with axSpA, and to compare treatment effects in subgroups with and without concomitant psoriasis and inflammatory bowel disease.

Methods: Thirty-nine patients with axSpA participated in a prospective, observational study and assessed at baseline, 6 and 12 months. Disease activity was measured using ASDAS and BASDAI, QoL was assessed via EQ VAS and HAQ, and work productivity was evaluated with WPAI.

Results: Infliximab resulted in significant reductions in ASDAS and BASDAI. QoL improved (HAQ decreased and EQ VAS increased). Work productivity also significantly improved, with decreases in absenteeism, presenteeism, activity impairment, and work productivity loss. Importantly, no significant differences were observed between subgroups.

Conclusion: This study provides real-world evidence that infliximab improved disease activity, quality of life, and work productivity in all patient groups. Although subgroup differences were not statistically significant, these findings suggest consistent therapeutic benefits across diverse clinical presentations of axSpA.

Introduction: Rapid and equitable access to antiviral biologics in outbreaks is constrained by bespoke manufacturing, lengthy trials, and uneven procurement. Biosimilar antivirals could change responsiveness from single-source supply to multi-manufacturer preparedness if regulatory and chemistry, manufacturing, and controls (CMC) platforms are leveraged.

Areas covered: Evidence on antiviral biologic classes, orthogonal analytics, critical quality attributes, pharmacokinetic/pharmacodynamic (PK/PD) biomarkers, regulatory convergence, value assessment, and manufacturing scale-up is summarized. Platform CMC and tech-transfer enablers (e.g. single-use, modular/distributed facilities) are described alongside integration of dynamic transmission models with distributional cost-effectiveness analysis to address equity. The review evaluates how high-resolution analytical similarity, combined with comparative clinical pharmacology, can reduce the need for comparative clinical efficacy studies in selected programs. paradigm. Databases and regulatory/health technology assessment portals were searched from January 2010 to 10 October 2025. Predetermined criteria with structured extraction and consensus resolution were utilized for dual screening.

Expert opinion: The field is moving toward PK/PD-anchored, analytics-first pathways that, with thorough mapping of structure - function relationships, may limit the need for Phase III trials. Pre-specified PD/analytic packages are provided for each modality/virus, along with reference product batch libraries, bridging plans, reliance agreements, and standing commission regulations to operationalize this approach in an emergency.

Introduction: Zolbetuximab, the first monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved as first-line treatment for patients with HER2-negative and CLDN18.2-positive gastric or gastroesophageal junction cancers, offering new hope to patients who previously derived limited benefit from molecular targeted therapies or immune checkpoint inhibitors.

Areas covered: This review presents clinical insights not fully captured in pivotal phase III trials, examining the clinicopathological characteristics of zolbetuximab-induced gastritis and the dynamics of CLDN18.2 expression during treatment. It further explores key clinical challenges - including standardized patient selection, management of gastrointestinal toxicities, and optimization of treatment sequencing - while providing an overview of recent advances in next-generation CLDN18.2-targeted strategies such as antibody - drug conjugates, bispecific antibodies, and CAR-T cell therapies.

Expert opinion: CLDN18.2-targeted therapy has demonstrated the therapeutic feasibility of targeting non-oncogenic drivers, representing a paradigm shift in gastric cancer treatment. Next-generation modalities such as ADCs, bispecific antibodies, and CAR-T cell therapies have shown efficacy even in patients with lower CLDN18.2 expression, suggesting potential to expand treatment eligibility. Moving forward, deeper understanding of gastrointestinal toxicities associated with CLDN-targeted therapies, elucidation of resistance mechanisms, and development of rational combination strategies will be essential to maximize therapeutic benefit in patients with CLDN18.2-positive gastric cancer.

Introduction: The rapid development and approval of biosimilars in the US offer a critical opportunity to improve the affordability and accessibility of biologic therapies.

Areas covered: This targeted literature review was conducted using PubMed to examine the broad impact of biosimilars on the US health system, focusing on payers, healthcare professionals, and patients within oncology and inflammatory disease settings. Literature published between 1 January 2016, and 1 December 2024, was analyzed.

Expert opinion: Existing research primarily addresses clinical equivalence to reference biologics and safety of switching, with a paucity in data demonstrating broader patient population benefits of biosimilars. Cost savings from biosimilars are described, but there is a lack of evidence that these savings translate into improved access or earlier use of biologics, or whether budgetary reallocations enable access to other innovative treatments. While biosimilars are expected to reduce spending and expand treatment options, data on their extended stability and real-world outcomes are scarce. In conclusion, biosimilars offer potential to reduce healthcare costs and improve access to biologic therapies. Further research is needed to fully establish their holistic benefits across patient populations. This would enable a better understanding of how biosimilar adoption influences real-world treatment access, clinical and system-wide outcomes.

Introduction: Oncolytic virus (OV) therapy represents a promising approach currently undergoing (pre)-clinical testing for several cancers. Until recently, it was thought that the tropism of oncolytic viruses was restricted to epithelial cancer cells unless they were modified to target additional cell types. It has now become evident that some OVs possess a natural ability to target cancer-associated fibroblasts (CAFs). CAFs are strongly highlighted in supporting cancer progression and impeding anti-cancer therapeutics. Therefore, targeting CAFs in addition to tumor cells could enhance therapy efficacy.

Areas covered: To date, the molecular determinants of tumor cell permissiveness to OV therapy have been thoroughly investigated. The recent notion that CAFs could also be a target for OVs highlights the importance of a comparable understanding of what makes CAFs permissive to OVs. This review explores the various molecular pathways and molecules that may affect the susceptibility of CAFs to OV infection and lysis. We discuss the potential impact of virus entry receptors, microRNAs, Ras and PI3K/AKT signaling, p53 status and type I interferon signaling.

Expert opinion: Further scrutinizing the factors that influence sensitivity of CAFs to OVs can help to identify targets for therapy optimization, especially in tumors with a high abundance of CAFs.

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have rapidly become an integral part of the treatment landscape for relapsed or refractory lymphomas. While early clinical trials demonstrated impressive response rates in patients with multiply relapsed disease and improved outcomes in those with disease refractory to first-line treatments, subsequent longer follow-up has revealed the occurrence of both early and late relapses, as well as the emergence of delayed toxicities.

Areas covered: Ten years after the initiation of the pivotal phase I/II trials that led to the approval of CD19-directed CAR T-cell therapies for large B-cell lymphoma (LBCL), extended follow-up data is now available. This review focuses on the long-term outcomes and toxicities of these therapies, as well as challenges to durable responses and future directions.

Expert opinion: Long-term follow-up has confirmed the curative potential of CAR T-cell therapy in relapsed or refractory LBCL. Toxicities are generally manageable, and although infections remain an important cause of non-relapse mortality, standardized prophylactic approaches can mitigate risk. Advances in CAR T-cell engineering and administration are likely to enhance treatment effectiveness, expand indications, and improve patient outcomes.