Expert Opinion on Biological Therapy最新文献

Introduction: Adding monoclonal antibodies to chemotherapy drastically changed the landscape of advanced colorectal cancer. The prediction of benefit from anti-EGFR therapies is mainly based on the absence of mutations in RAS and BRAF genes, the primary tumor sidedness and microsatellite MSS/MSI status. Molecular hyperselection may optimize the outcome of patients receiving anti-EGFR while detecting additional resistance alterations, both in chemo-naïve and in chemo-refractory settings.

Areas covered: Our review focuses on negative molecular hyperselection, both on tissue samples and ctDNA, and the impact of this further patient selection on response rate and survival outcomes. We searched electronic database, selecting relevant English-language publications from 2017 to 2024.

Expert opinion: Negative hyperselection beyond RAS and BRAF in advanced colorectal cancer appears to be a powerful tool for predicting outcomes to anti-EGFR therapy and spare patients from unnecessary treatment. This improvement appears in both naïve and pre-treated patients. However, data come mainly from retrospective studies. Therefore, to validate and integrate these findings in the clinical practice, prospective studies should be conducted. It will be interesting to elucidate the role of ctDNA in this setting and the choice of molecular techniques, considering costs and accessibility, to guarantee its implementation in the clinic.

Objectives: Many biosimilars have been approved in both the United States of America (U.S.A.) and European Union (EU). We aim to highlight how regulatory challenges and divergent requirements between both agencies exist.

Methods: A comprehensive review of biosimilars approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) was conducted. We aimed to highlight similarities and differences in approaches taken by the agencies regarding the use of non-local (i.e. non -US and non-EU) reference medicinal products in biosimilar development. A search of the six most frequent classes of biosimilars authorized (cutoff date: 12 June 2024) by these agencies were identified and their public assessment reports reviewed.

Results: The review highlighted that pharmacokinetic (PK) bioequivalence studies are often replicated, the current process is inefficient and not entirely necessary when critical quality attributes are considered.

Conclusion: This article provides a comparative analysis of biosimilar approvals in EU and US regulatory agencies, focusing on non-local reference medicinal product (RMP) utilization and bioequivalence demonstration. The findings contribute to literature on biosimilar development and regulatory considerations, enhancing understanding of harmonization opportunities in biosimilar approval processes, potentially improving global access to high-quality, cost-effective biosimilars.

Background: Research has signaled the need for reformed biosimilar policy frameworks that adopt a behavioral approach, are informed by consensus-generating strategies and thus better align with the requirements of local healthcare communities.

Research design and methods: Through a series of co-creation workshops, the current study explores the feasibility of applying learnings from Collective Action Theory to formulate evidence-based multistakeholder-supported policy recommendations.

Results: Insights from the conducted workshops indicate that future policy frameworks would benefit from: 1) a working system of incentives and rewards aligned with stakeholder needs; 2) evaluating the cost-benefit balance for stakeholders prior to policy implementation; 3) involving multistakeholder panels in policy co-design; 4) adopting a long-term vision; 5) fostering coordination at the interface between levels of governance; 6) defining shared goals and efficient systems to monitor policy compliance; and 7) using policy outcome data to adapt current policy frameworks based on evolving needs. The incorporation of these elements to policies is expected to help prioritize long-term sustainable solutions, and balance short-term gains and long-term objectives in biosimilar markets.

Conclusions: This study constitutes a first approach to developing multistakeholder-supported principles for sustainable biosimilar markets. This is a necessary step toward generating stakeholders' consensus on biosimilar policies.

Introduction: X-linked myotubular myopathy (XLMTM) is a life-threatening congenital disorder characterized by severe respiratory and motor impairment. This disease presents significant therapeutic challenges, with various strategies being explored to address its underlying pathology. Among these approaches, gene replacement therapy has demonstrated substantial functional improvements in clinical trials. However, safety issues emerged across different therapeutic approaches, highlighting the need for further research.

Areas covered: This review provides a comprehensive analysis of the data gathered from natural history studies, preclinical models and clinical trials, with a particular focus on gene replacement therapy for XLMTM. The different therapeutic strategies are addressed, including their outcomes and associated safety concerns.

Expert opinion: Despite the encouraging potential of gene therapy for XLMTM, the occurrence of safety challenges emphasizes the urgent need for a more comprehensive understanding of the disease's complex phenotype. Enhancing preclinical models to more accurately mimic the full spectrum of disease manifestations will be crucial for optimizing therapeutic strategies and reducing risks in future clinical applications.

Introduction: The relationship between psoriasis, immunomodulatory therapies, and the risk of malignancies is complex and still debated. The scarcity of evidence in this field makes clinicians hesitate to prescribe biological therapies for 'difficult-to-treat' patients.

Areas covered: Based on a comprehensive MEDLINE/PUBMED search of articles published up to November 2024, this review synthesizes the current evidence on the association between psoriasis and cancer. This review specifically addresses four key aspects: the overall cancer risk in psoriatic patients, the potential role of cytokines involved in psoriasis pathogenesis in tumor development, the association between biological therapies and the incidence of new malignancies in this population, and the risk of cancer recurrence or progression in patients with a history of malignancy who are treated with biologics.

Expert opinion: Biological therapies do not significantly elevate malignancy risk compared to non-biological treatments or the general population. Evidence is also reassuring for patients with prior malignancy, showing no tumor progression or recurrence. These findings support the timely use of biological treatments in 'difficult-to-treat' patients. Regular cancer screenings and risk-factor minimization should always be recommended for psoriatic patients undergoing immunomodulatory therapies. Multidisciplinary management involving oncologists is suggested, particularly for patients with active and advanced oncological disease.

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 long-term 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: 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: 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.