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-...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.
Azevedo RS, Nooruddin Z, Bhatia S
… +10 more, Finn L, Davis C, Alsfeld LC, Subbiah S, Norkin M, Ulrickson M, De La Fuente A, Larson ML, Budak-Alpdogan T, Pemmaraju N
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...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.
INTRODUCTION: Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are aggressive hematologic malignancies with poor outcomes, particularly in relapse...INTRODUCTION: Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN) are aggressive hematologic malignancies with poor outcomes, particularly in relapsed/refractory settings. CD123, the interleukin-3 receptor alpha chain, is highly expressed on leukemic blasts and leukemia stem cells, making it an attractive therapeutic target with limited expression on normal hematopoietic cells. CD123-directed therapies - including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapies - are under active investigation. AREAS COVERED: This review details the preclinical rationale, clinical development, efficacy, and toxicity of CD123-targeted therapies. It discusses completed and ongoing clinical trials for agents such as tagraxofusp, pivekimab sunirine, flotetuzumab, vibecotamab, and investigational CAR T-cell therapies (e.g. MB-102, UCART123v1.2). Toxicities, including myelosuppression, cytokine release syndrome (CRS), and hepatotoxicity - are characterized in detail, with attention to mitigation strategies. Future directions highlight combination regimens, switchable CAR designs, and biomarker-driven personalization. EXPERT OPINION: CD123-targeted therapy represents a promising yet challenging frontier in treating high-risk leukemias. While clinical activity has been demonstrated, especially in BPDCN, therapeutic durability and safety remain hurdles. Precision in antigen targeting, combination strategies, and toxicity management will be critical for successful integration of CD123-directed therapies into standard clinical practice.
INTRODUCTION: The antibody therapeutic landscape has been dominated by monoclonal antibodies (mAbs) since the early 2000s, leading to polyclonal antibodies (pAbs) assuming a less prominent role in clinical use. However,...INTRODUCTION: The antibody therapeutic landscape has been dominated by monoclonal antibodies (mAbs) since the early 2000s, leading to polyclonal antibodies (pAbs) assuming a less prominent role in clinical use. However, the multiepitope targeting capability of pAbs has generated renewed interest over the last five years. Emerging technologies such as recombinant antibody pools are prompting a revisit of the distinction between traditional mAb and pAb therapies. AREAS COVERED: Using listed FDA-approved polyclonal therapies as a basis for our literature searches, we explore the applications of current pAb therapies and examine whether mAbs may eventually replace them. We also discuss the costs and cost-effectiveness of directly competing mAb and pAb therapies for a variety of clinical indications. Finally, we review emerging technologies, such as glyco-humanized and recombinant pAbs, covering their modes of action, manufacturing approaches, and current clinical trial statuses. EXPERT OPINION: The current clinical pAb therapy landscape is varied, evolving, and continues to be challenged by mAbs. For the pAb therapies explored in this review, multiple competing mAb alternatives are progressing toward clinical approval. Future hybrid technologies like recombinant pAbs may allow multiple epitope targeting while achieving enhanced safety profiles and batch-to-batch consistency; however, their cost-effectiveness remains uncertain.
BACKGROUND: To evaluate early real-world clinical outcomes on the safety and efficacy of the ranibizumab biosimilar (Oceva, Sun Pharmaceuticals, India). RESEARCH DESIGN AND METHODS: A multicenter, retrospective, uncontro...BACKGROUND: To evaluate early real-world clinical outcomes on the safety and efficacy of the ranibizumab biosimilar (Oceva, Sun Pharmaceuticals, India). RESEARCH DESIGN AND METHODS: A multicenter, retrospective, uncontrolled observational study evaluating data from 404 eyes that received a total of 742 intravitreal injections of the ranibizumab biosimilar (Oceva 0.5 mg) across four centers in India, administered between August 2024 and May 2025 in variable approved and off label indications. Of the total eyes, 288 were treatment-naïve naïve, while 116 eyes were previously treated. RESULTS: The mean (SD) follow-up was 14.39 ± 12.5 weeks. The mean BCVA improved significantly from 0.87 to 0.59 LogMAR ( < 0.0001; d = 0.61), and mean CFT reduced from 406.8 µm to 306.5 µm ( < 0.0001; d = 0.66). Naïve eyes showed greater improvements than previously treated ones. No serious ocular or systemic adverse events were observed. CONCLUSIONS: The preliminary real-world data from this limited early series suggest that ranibizumab biosimilar (Oceva) appears to be efficacious and safe across the approved indications. However, long-term data with a larger population are needed to further strengthen the findings of this study.
INTRODUCTION: Small-cell lung cancer (SCLC) is a rapidly progressive form of cancer often expressing DLL3. Tarlatamab is a bispecific antibody which blocks DLL3-related downstream pathways and activates antitumor host im...INTRODUCTION: Small-cell lung cancer (SCLC) is a rapidly progressive form of cancer often expressing DLL3. Tarlatamab is a bispecific antibody which blocks DLL3-related downstream pathways and activates antitumor host immunity. It is currently authorized in the U.S.A. for the treatment of extensive SCLC. AREAS COVERED: This is a review evaluating the basic pharmacology and clinical data regarding tarlatamab. Most data come from SCLC; in the other two diseases, tarlatamab is in early clinical development. EXPERT OPINION: Tarlatamab is an effective therapy mainly in relapsed/progressed SCLC, and its assessment in limited SCLC alone or combined with other therapies is supported by the existing data.
BACKGROUND: Biologic agents have significantly improved psoriasis treatment, but patient responses exhibit considerable heterogeneity, highlighting the urgent need for practical predictive biomarkers of therapeutic effic...BACKGROUND: Biologic agents have significantly improved psoriasis treatment, but patient responses exhibit considerable heterogeneity, highlighting the urgent need for practical predictive biomarkers of therapeutic efficacy. RESEARCH DESIGN AND METHODS: This prospective cohort study enrolled 422 psoriasis patients and 150 healthy controls. Sixteen CPD parameters were measured using a hematology analyzer. We analyzed associations between baseline CPD and disease severity as well as inflammatory markers, assessed their predictive value for treatment response over 48 weeks of biologic therapy, and monitored early dynamic changes in CPD and their relationship with treatment response in 169 patients. RESULTS: All CPD parameters were significantly elevated in psoriasis patients compared to healthy controls (all < 0.001). Baseline mean lymphocyte volume (MN-V-LY) demonstrated sustained negative correlations with PASI improvement rates from weeks 4 to 48 (ρ = -0.278 to -0.449, all < 0.001). Early reduction in monocyte volume heterogeneity (SD-V-MO) was significantly associated with long-term efficacy (ρ = -0.355 to -0.546, all < 0.001). CONCLUSIONS: As simple, standardized hematological parameters, CPD show potential for clinical application in predicting biologic therapy response in psoriasis.
INTRODUCTION: Bispecific antibodies (BsAbs) are a novel class of immunotherapy agents that engage endogenous T cells to target and eradicate malignant B cells by simultaneously binding CD3 and CD20. BsAbs such as epcorit...INTRODUCTION: Bispecific antibodies (BsAbs) are a novel class of immunotherapy agents that engage endogenous T cells to target and eradicate malignant B cells by simultaneously binding CD3 and CD20. BsAbs such as epcoritamab, glofitamab, and mosunetuzumab have demonstrated substantial efficacy across both aggressive and indolent B-cell non-Hodgkin lymphomas (B-NHL), with largely manageable safety profiles. Their off-the-shelf administration offers a practical alternative to CAR T-cell therapy, particularly for patients who are transplant-ineligible or lack access to cellular approaches. AREAS COVERED: This review provides a comprehensive overview of BsAbs in B-NHL. We detail pivotal studies in relapsed/refractory (R/R) DLBCL, FL, and MCL, highlighting single-agent outcomes and emerging combination strategies. Approaches incorporating BsAbs into cytotoxic backbones and antibody-drug conjugates, as well as chemotherapy-free regimens such as BsAbs combined with lenalidomide, are discussed. We also examine their potential to address poor-risk disease features and historically refractory subsets. EXPERT OPINION: BsAbs represent a major advance in B-NHL, offering high rates of deep remission with predictable safety and outpatient feasibility. As trial data continues to mature, BsAb-based regimens are poised to become foundational across multiple lines of therapy, reshaping expectations for patients with both aggressive and indolent lymphomas.
Arık SD, Doğru Kılınç A, Menentoğlu B
… +10 more, Başer Taşkın B, Dudaklı A, Kavrul Kayaalp G, Akgün Ö, Türkmen Ş, Özaslan NZ, Şahin N, Çakan M, Sözeri B, Aktay Ayaz N
OBJECTIVE: To evaluate indications, clinical response, outcomes, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) in a multicenter cohort. METHODS: This retros...OBJECTIVE: To evaluate indications, clinical response, outcomes, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) in a multicenter cohort. METHODS: This retrospective multicenter study included 29 patients with JDM who received IVIG. Demographic data, clinical features, laboratory parameters, and standardized disease activity scores were recorded at disease onset, before and after IVIG treatment, and at final follow-up. Treatment response and adverse events were analyzed. RESULTS: IVIG was initiated a median of 1.2 months (IQR: 0.1-18.9) after diagnosis and continued for a median of 8.2 months (IQR: 5.6-21.6). Indications included refractory muscle weakness, persistent skin disease, calcinosis, and interstitial lung disease (ILD). IVIG therapy was associated with significant improvements in disease activity measures and laboratory parameters ( < 0.001). Calcinosis partially or completely resolved in 3 of 6 patients, while no change was observed in the single ILD case. IVIG was well tolerated, with only mild adverse effects. CONCLUSION: IVIG appears to be a safe and effective treatment option for JDM, particularly in refractory or skin-predominant disease. Although causal inferences are limited by the retrospective design and the absence of a control group, these real-world findings support the inclusion of IVIG in an individualized treatment approach.
INTRODUCTION: Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contri...INTRODUCTION: Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contribute to immune surveillance and regulation. Their therapeutic potential lies in their ability to act across donor barriers with a reduced risk of graft-related complications; however, clinical translation remains challenging due to tumor immune evasion and limited persistence in suppressive environments. AREAS COVERED: This review summarizes the biological roles of NK cells in cancer immunity and examines recent therapeutic approaches that harness their cytotoxic and regulatory properties. We discuss barriers to clinical application, including immune suppression, antigen loss, and manufacturing limitations. In addition, we highlight emerging strategies, such as gene editing, rational combination therapies, and standardized clinical trial designs, aimed at improving therapeutic efficacy. EXPERT OPINION: NK cell-based therapies represent a promising avenue in cancer immunotherapy but require carefully designed solutions to overcome their inherent limitations. Advances in biomarker-guided patient selection, integration with existing treatment modalities, and international collaboration will be critical for translating NK cell biology into effective and durable clinical outcomes.
INTRODUCTION: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder and has a considerable impact on patients' quality of life. Dupilumab, the first biologic approved for moderate-to-severe AD, is a hu...INTRODUCTION: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder and has a considerable impact on patients' quality of life. Dupilumab, the first biologic approved for moderate-to-severe AD, is a human monoclonal antibody targeting the interleukin (IL)-4 receptor α, thereby blocking both IL-4 and IL-13 signaling, key drivers of type 2 inflammation in AD. Its introduction has marked a paradigm shift in the management of AD and paved the way for future therapies. As real-world evidence on biologics and Janus kinase (JAK) inhibitors is rapidly emerging, comprehensive and up-to-date reviews are important. AREAS COVERED: This review primarily summarizes real-world data on dupilumab, with a focus on its effectiveness and safety in clinical practice, highlighting recent findings and their implications for optimizing patient management. EXPERT OPINION: Real-world evidence consistently confirms the high effectiveness, favorable safety profile, and long-term treatment durability of dupilumab across various patient subgroups, including children, elderly, and patients with different underlying immune and genetic profiles. Additionally, dupilumab has demonstrated beneficial effects in patients with comorbid asthma and food allergies. Emerging data further support its potential safety during pregnancy, breastfeeding, and (non-)live vaccinations. Dose tapering is often successful and lowers the socio-economic impact of dupilumab.
INTRODUCTION: Interleukin (IL)-23 is a cytokine implicated in the pathogenesis of ulcerative colitis (UC). Guselkumab, a selective IL-23 antagonist, was approved for the treatment of moderately-to severely active UC in 2...INTRODUCTION: Interleukin (IL)-23 is a cytokine implicated in the pathogenesis of ulcerative colitis (UC). Guselkumab, a selective IL-23 antagonist, was approved for the treatment of moderately-to severely active UC in 2024/5. AREAS COVERED: The review briefly summarizes the pathophysiology of the IL-23 pathway and summarizes the available evidence on the efficacy and safety of guselkumab in UC. We discuss future challenges and clinical dilemmas in the use of guselkumab. EXPERT OPINION: Guselkumab has demonstrated efficacy across all endpoints with a favorable safety profile. No direct comparisons are available between individual IL-23 antagonists or with ustekinumab, the IL-12/23 antagonist, which limits decision-making in clinical practice. Combining two biologics as advanced combination treatment is an attractive strategy to break the therapeutic efficacy ceiling in UC - a proof-of-concept phase 2 trial combining guselkumab and golimumab has shown promise, the combination is currently undergoing evaluation in a larger ongoing trial.
BACKGROUND: Pediatric rheumatic diseases impose substantial significant physical, emotional, and social burdens. Biologic therapies have revolutionized disease management; however, few data exist exploring caregivers' li...BACKGROUND: Pediatric rheumatic diseases impose substantial significant physical, emotional, and social burdens. Biologic therapies have revolutionized disease management; however, few data exist exploring caregivers' lived experiences with pediatric biologic therapy. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted between August and October 2025 across three pediatric rheumatology centers in Türkiye. Primary caregivers of 156 children receiving biologic disease-modifying antirheumatic drugs (bDMARDs) for ≥3 months completed structured questionnaires assessing demographics, knowledge, perceptions, emotions, treatment experiences, satisfaction, and support needs. RESULTS: Among caregivers, 42% initially reported fear and 33% expressed trust or reliance upon treatment recommendation. Overall satisfaction with clinic services was high (98%), and 79% perceived marked improvement in their child's well-being and daily functioning. Perceived insufficiency of information was associated with increased fear and concern ( = 0.005). Subcutaneous, weekly regimens predominated, and mothers more often reported difficulty with administration ( = 0.042). Longer treatment duration was associated with more positive perceptions ( = 0.049), while adverse events were linked to lower perceived efficacy ( = 0.035). CONCLUSION: Caregiver perceptions significantly affect adherence and satisfaction. Structured caregiver education and psychosocial support should be integrated into routine pediatric rheumatology practice to strengthen adherence and family-centered care.
INTRODUCTION: Talquetamab is a GPRC5DxCD3 T-cell-engaging bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma. GPRC5D represents a novel and emerging target in antimyeloma therapy, and...INTRODUCTION: Talquetamab is a GPRC5DxCD3 T-cell-engaging bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma. GPRC5D represents a novel and emerging target in antimyeloma therapy, and there is substantial drug development for new therapies targeting this antigen. AREAS COVERED: Herein, we review the efficacy, safety, and future development directions of talquetamab, including emerging talquetamab-based combination regimens and ongoing clinical trials. We will also review the growing landscape of GPRC5D-targeting immunotherapies in development for multiple myeloma, including CAR-T and trispecific antibodies. EXPERT OPINION: Talquetamab, a GPRC5D-targeting bispecific antibody, was FDA-approved in 2023 for relapsed/refractory multiple myeloma after 4 or more prior lines of therapy. In contrast to the historic overall response rate (ORR) of 29.5%, talquetamab monotherapy achieved a promising ORR of ~70% in a triple-class-exposed population. Real-world evidence supports talquetamab as a bridging therapy to CAR-T. Notable adverse drug reactions include CRS, dysgeusia, nail/skin toxicities, and infections, which are often manageable but can be persistent. Sequencing studies suggest talquetamab retains efficacy before or after BCMA-directed therapies without diminishing effectiveness. Potential future directions for talquetamab include combination regimens with other antimyeloma therapies. Additional GPRC5D-directed therapies are also under development, including trispecific antibodies and CAR-T.