Expert Opinion on Biological Therapy最新文献

Introduction: Bispecific antibody therapies, primarily targeting B-cell maturation antigen (BCMA), have shown remarkable outcomes in the treatment of heavily pretreated patients with multiple myeloma (MM). However, there are no current head-to-head trials informing practice for selection or sequencing of optimal T cell redirection strategies in later lines of therapy. Linvoseltamab is a novel BCMA-targeted bispecific antibody that was recently evaluated in the phase 1/2 LINKER-MM1 trial and is currently pending formal regulatory approval.

Areas covered: In this drug evaluation, we review efficacy and toxicity profiles of linvoseltamab in the context of currently approved bispecific antibody therapies for MM. Specifically, we highlight differences in dosing strategy, cytokine release syndrome (CRS) kinetics, and indirect efficacy comparisons between trials of linvoseltamab and other bispecific antibodies.

Expert opinion: Linvoseltamab has a similar efficacy profile with favorable CRS incidence and time-to-onset compared to other approved bispecific antibodies. Pending final regulatory approval and labeling, further real-world analyses are needed to evaluate its final role in the evolving landscape of T cell redirection therapy for MM.

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, systemic, autoinflammatory disease characterized by the eruption of sterile pustules, often accompanied by more general symptoms, such as fever, fatigue, and a burning sensation in the skin. GPP can be potentially life-threatening, if untreated, as it can lead to complications, such as sepsis and heart failure.

Areas covered: In this literature review and expert opinion article, we provide an overview of the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of GPP. Eleven dermatologists representing seven different Italian regions considered relevant evidence in the literature to discuss the current diagnosis and treatment of GPP. The expert panel of dermatologists identified several weaknesses in the current clinical management of GPP.

Expert opinion: There is an inconsistent definition and classification of the disease across the literature, which can lead to misdiagnosis and delay in disease treatment. Furthermore, there are no international and standardized clinical guidelines on disease management, especially in Europe. There is a profound need for the development of novel therapeutic agents with sustained efficacy to decrease the impact of the comorbidities and mortality associated with GPP, prevent the onset of complications, and support the unmet needs of these patients.

Introduction: The human endometrium is a highly regenerative tissue that contains mesenchymal stem/stromal cells (MSCs). These MSCs are sourced via office-based biopsies and menstrual fluid providing a less invasive and readily available option for cell-based therapies. This review provides an update on endometrial-derived MSCs as a treatment option for gynecological diseases.

Areas covered: This narrative review covers the characterization and therapeutic mechanisms of endometrium biopsy-derived MSCs (eMSCs) and menstrual fluid-derived mesenchymal stromal cells (MenSCs), highlighting similarities and differences. It also covers studies of their application in preclinical animal models, and in clinical trials as potential cell-based therapies for gynecological diseases.

Expert opinion: eMSCs and MenSCs from a homologous tissue source have the potential to promote regenerative activity as a treatment for gynecological diseases. Both eMSCs and MenSCs demonstrate therapeutic benefits through their paracrine activity in tissue regeneration, immunomodulation, angiogenesis and mitigating fibrosis. Further research is essential to establish standardized isolation and characterization protocols, particularly for heterogeneous MenSCs, and to fully understand their mechanisms of action. Implementing SUSD2 magnetic bead sorting for purifying eMSCs from endometrial tissues and menstrual fluid is crucial for their use in future cell-based therapies. Optimization of production, storage and delivery methods will maximize their therapeutic effectiveness.

Introduction: The amyloid cascade hypothesis postulated that the accumulation of amyloid-β (Aβ) was the first step of the Alzheimer's disease (AD) pathological process. Effective reduction of Aβ plaque load by numerous drug candidates, among which anti-Aβ monoclonal antibodies, has produced discussible clinical successes and several failures. It was questioned whether Aβ may be the principal AD pathogenic factor and a valid therapeutic target and if targeting Aβ different species could make the difference.

Areas covered: This review article summarized successes and failures of anti-Aβ monoclonal antibody therapy for AD, delineating the latest advances for their clinical development also according to their target engagement and downstream biomarkers.

Expert opinion: The preliminary success of the recent Phase III randomized clinical trials (RCTs) of lecanemab, donanemab, and remternetug, and lessons learned from the failure of previous anti-Aβ monoclonal antibodies RCTs, provided critical evidence to support the role of Aβ in AD pathogenesis. The loss of free Aβ instead of an Aβ toxicity may promote AD neuropathology. Cerebrospinal fluid analyses (i.e. increases in Aβ_1-42) may indicate a potential benefit of anti-Aβ monoclonal antibodies in AD and downstream biomarkers should be considered for providing comprehension in cognitive and clinical efficacy of future AD RCTs.

Introduction: Melanoma has become the poster child for transformative outcomes in advanced malignancy from the use of immunotherapy over the last 10-15 years with median survival improving from ~ 1 to > 5 years. With the increasing repertoire of immune checkpoint inhibitors (ICI) and other novel immunotherapeutic approaches, integrating and sequencing treatments to create new paradigms has gained prominence, with focus on optimizing toxicity management and complex scenarios such as immunotherapy resistance, brain metastases, fertility, and duration of follow-up.

Areas covered: In this review, we summarize the progress and emerging evidence in melanoma treatments to date and consider management and possible future directions to improve outcomes for above-mentioned specific patient cohorts.

Expert opinion: Personalized care with integration of novel prognostic and predictive biomarkers is the way forward in tailoring not only patient selection and choice of therapy, but also duration of treatment and surveillance to allow for early recurrence detection and access to newer therapies such as tumor infiltrating lymphocytes (TIL) to maximize the curative fraction of melanoma patients. Further research is needed in optimizing ICI and other immunotherapy toxicity management, including reducing steroid exposure for better patient outcomes and preserving quality of life.

Introduction: Migraine is a disabling neurological disorder with a complex neurobiology. It appears as a cyclic disorder of sensory processing, affecting multiple systems beyond nociception. Overlapping mechanisms, including dysfunctional processing of sensory input from brain structures are involved in the generation of attacks.

Areas covered: This review provides a comprehensive synthesis on migraine neurobiology, which was additionally informed by search of research databases (PubMed, ClinicalTrials.gov). Findings from the most recent literature are integrated in a pathophysiological framework. By combining mechanistic insights and clinical trial data, this review highlights the trajectory of precision medicine in migraine treatment, offering a perspective on the near future of targeted and individualized therapeutic strategies.

Expert opinion: Recent advances in migraine neurobiology offer potential solutions to longstanding challenges. While targeted CGRP therapies have shown promise by addressing specific mechanisms, the pathophysiology of migraine suggests that combination therapies targeting multiple pathways could be beneficial in migraine prevention. The growing diversity of treatment options presents challenges in therapy selection, underscoring the need for predictive biomarkers. These innovations can optimize treatment strategies and improve patient outcomes. As the field progresses, personalized, multimodal approaches are poised to become the standard of care, significantly advancing precision medicine in this area.

Introduction Choroideremia is a rare disease with a significant disease burden. Gene-supplementation methods for choroideremia gene therapy have been the most successful form of gene therapy thus far. Areas covered The aim of the current review is to provide an overview of current progress of gene therapy trials to date, with a focus on potential and pitfalls of such trials. We propose a novel end point that may be clinically meaningful for obtaining regulatory approval in subsequent clinical trials. Additionally, we offer recommendations for further optimization of surgical techniques. Expert opinion Lessons learnt from this phase 3 clinical trial, encompassing optimal vector design, delivery techniques, patient selection criteria, and longterm safety profiles can be used in the development of treatments for polygenic retinal disorders, which may necessitate a more nuanced approach due to genetic complexity.

Introduction: Clinical experience with anti-interleukin (IL)-5 biologic therapies for severe asthma has been increasing, alongside deeper and broader research focusing on the role of IL-5 and the IL-5 targeted mepolizumab. This review aims to provide an update of the evidence on the role of IL-5 and mepolizumab, with discussions of the benefits of mepolizumab and its future potential, to promote the comprehension of the pathophysiology and therapeutic approaches to asthma.

Areas covered: For this narrative review, we conducted a database search in PubMed and Embase using the keywords 'IL-5' and 'mepolizumab,' focusing on randomized controlled trials and real-world studies up to September 2024. An overview of the pathogenesis of severe asthma, new insights on the role of IL-5 and mepolizumab, and the evidence on the efficacy and safety of mepolizumab in the treatment of severe eosinophilic asthma is provided, and its benefits in clinical remission and future applications are also discussed.

Expert opinion: Mepolizumab holds considerable promise in asthma treatment due to its mechanism of action and multiple potential benefits. In clinical practice, it may be worth considering the exploratory initiation of mepolizumab add-on treatment from the time of medium-dose inhaled glucocorticosteroid use.

Introduction: Revolutionary drugs have been developed and approved in the last 5 years for the treatment of hereditary angioedema (HAE). Increased knowledge of HAE pathophysiology has led to the development of innovative drugs for self-administered on-demand therapy and for short- and long-term prophylaxis (LTP). This has rendered possible a personalized approach for patients, allowing greater control of symptoms, better quality of life and reduction in the incidence of adverse effects linked to old treatments.

Areas covered: In this review we have highlighted which treatments are currently approved for HAE and some of the promising future therapies under development.

Expert opinion: While the first generation of approved treatments improved disease control for most patients, innovative therapies may allow individualized action plans and reduce complexity of treatment. Switching therapies due to insufficient efficacy, patient preference or adverse events is becoming progressively feasible and common. New LTPs may lead to the achievement of attack-free remission, allowing us to hopefully reach complete disease control for all patients and further improving their quality of life. In particular, LTPs with longer administration intervals, and on-demand therapies administered via the oral route will have a key role and will set more prominent targets for the upcoming drugs.