INTRODUCTION:HS is an inflammatory skin condition that causes abscesses, nodules, and tunnels in intertriginous areas. Treatment consists of multimodal therapy such as topical and systemic antibiotics, washes and ointments, hormonal modulation, retinoids, surgery, and recently biologic therapy. The FDA approved three biologics for HS in the last 10 years, although novel options are needed for recalcitrant disease. AREAS COVERED:A comprehensive search of the National Institutes of Health (NIH) Clinical Trials database was performed in April 2025, with an updated search in October 2025. Trials were limited to hidradenitis suppurativa, phase II or III, and a status of not yet recruiting, recruiting, active, completed, or terminated. Data were supplemented with a PubMed query and an internet search for data and press releases from companies. Results include 52 phase 2 and 16 phase 3 studies. EXPERT OPINION:Biologics serve as a steppingstone to a new age of therapy for HS. Investigations are needed for recalcitrant disease, to minimize adverse events, and provide personalized treatment. Compounds with promise include JAK inhibitors, while other compounds await results, and others limited by small sample sizes and non-randomized study designs. Future trials should focus on comparative drug designs and ensuring fair access for all, particularly patients with the highest disease burden.
INTRODUCTION:Claudins are integral components of tight junctions with emerging roles in cancer biology. Dysregulated claudin expression during malignant transformation exposes these proteins on the tumor cell surface, creating opportunities for targeted therapy. Claudin-6, an oncofetal protein largely absent from normal adult tissues, is aberrantly expressed in a significant subset of ovarian cancers, making it an attractive therapeutic target. AREAS COVERED:This review summarizes the biological rationale for targeting claudin-6 in ovarian cancer and evaluates current therapeutic strategies, including monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engagers, CAR-T cells, and CAR-NK cells. The analysis is based on a structured literature search conducted in major biomedical databases, including MEDLINE (via PubMed), EMBASE, Scopus, and Web of Science, as well as ClinicalTrials.gov for ongoing studies. EXPERT OPINION:Claudin-6-targeted therapies represent a promising advancement for patients with recurrent or platinum-resistant ovarian cancer. Among current approaches, ADCs appear closest to broad clinical applicability due to their potency and manageable safety profiles. Future success will depend on standardized diagnostic assays, biomarker-driven trial designs, and rational combination strategies to overcome resistance and maximize durable clinical benefit.
INTRODUCTION:Advanced gastroesophageal adenocarcinomas (GEAs) continue to represent an area in need of new drug development. Targeting human epidermal growth factor receptor-2 (HER2) in GEAs has been standard since 2010 and continues to be an area of further development. AREAS COVERED:Trastuzumab became the first targeted agent approved for GEA. Added to front-line fluoropyrimidine plus platinum chemotherapy in HER2+ metastatic disease, trastuzumab improved survival. Pembrolizumab was approved in HER2 positive GEA for those PD-L1 positive with modest benefit. Since trastuzumab's approval, other anti-HER2 agents had limited impact until 2021 with the FDA approval of trastuzumab deruxtecan. Trastuzumab deruxtecan represents an option after trastuzumab-based therapy fails. Other agents are currently being investigated. EXPERT OPINION:With the abundance of anti-HER2 therapies in the investigative pipeline, understanding key resistance mechanisms seen in HER2+ GEA will be the path to success. Technology advancements to provide real‑time precision medicine are likely in the coming years. We hope these advancements can help combat and/or understand some of the intratumoral heterogeneity, HER2 expression changes, and tumor microenvironment resistance pathways seen in HER2+ GEA.
INTRODUCTION:The amyloid cascade hypothesis provided a compelling rationale for Alzheimer's disease (AD) drug development, but many amyloid-β (Aβ)-targeted agents failed to show benefit. The present review article evaluated emerging Aβ-directed therapies, focusing on mechanisms, clinical efficacy, safety, and regulatory progress. AREAS COVERED:The recent approvals of lecanemab and donanemab offered the first convincing evidence that reducing Aβ burden can modestly slow cognitive decline in early AD. Beyond these first-generation monoclonal antibodies, the pipeline includes next-generation antibodies with enhanced brain penetration (trontinemab), therapies designed also for presymptomatic intervention (remternetug tested for secondary prevention), and novel approaches targeting galectin-3 to disrupt Aβ aggregation and neuroinflammation. Active immunotherapies like UB-311 and small molecules such as ALZ-801, avoiding amyloid-related imaging abnormalities (ARIA), broaden the therapeutic horizon with potentially safer and more accessible options, but with no proven efficacy. EXPERT OPINION:Clinical benefits for Aβ-centric therapies are modest, ARIA poses ongoing safety concerns, and high costs coupled with intensive monitoring limit accessibility. Regulators have begun to restrict approval to genetically defined subgroups according to apolipoprotein E genotype, underscoring the need for precision medicine. Therefore, while Aβ-centric therapies are incremental, they represent essential steps toward combination and precision strategies in the treatment of AD.
INTRODUCTION:Menstrual migraine is a common and disabling subtype of migraine, linked to hormonal fluctuations and characterized by attacks that are often more severe, longer lasting and less responsive to treatment than non-menstrual episodes. Despite its relevance, menstrual migraine remains underdiagnosed and undertreated. AREAS COVERED:This review examines the role of therapies targeting the calcitonin gene-related peptide (CGRP) pathway in menstrual migraine. We summarize current evidence on monoclonal antibodies and gepants, focusing on their efficacy in hormonally triggered attacks and their potential advantages over traditional treatments. EXPERT OPINION:CGRP-targeted therapies represent a promising mechanism-based approach for menstrual migraine, although their role is not yet fully defined. These treatments reduce overall migraine burden, but the perimenstrual component may remain relatively resistant. The lack of dedicated clinical trials is a major limitation. Among available options, gepants offer the greatest potential due to their flexibility for both acute and short-term preventive use. Future research should focus on time-specific treatment strategies and a broader understanding of the underlying biology, including the role of additional neuropeptides.
INTRODUCTION:Dravet syndrome (DS), a catastrophic developmental and epileptic encephalopathy primarily caused by SCN1A haploinsufficiency, remains largely refractory to current antiseizure medications. In recent years, gene-targeted therapies, including antisense oligonucleotides (ASOs)-and viral-based therapies, have emerged as promising disease-modifying strategies. AREAS COVERED:Preclinical in vitro and in vivo models demonstrated that ASO-mediated modulation of SCN1A can restore transcript and protein levels, normalize interneuron excitability, and extend survival. Key advances include the discovery of deep-intronic 'poison' exons expanding actionable ASO targets and the demonstration of long-term functional rescue after early-life administration. Complementary strategies, such as SCN8A modulation, SCN1A viral delivery, and tau suppression, further broadened therapeutic options. Clinically, the ASO STK-001 trial showed favorable safety, pharmacodynamic activity, and durable seizure reduction in Phase 1/2a and open-label extension trials, alongside improvements in adaptive behavior and cognition. EXPERT OPINION:ASO-based modulation of SCN1A represents a pivotal advance in DS therapy, translating robust preclinical efficacy into early clinical benefit. Optimization of dosing regimens, durability, and combinatorial approaches targeting parallel molecular pathways will be critical to realize precision gene therapy for DS. Viral gene therapy approaches constitute a promising therapeutic platform, but comprehensive validation will be essential to ascertain their immunogenic safety and demonstrate clinical efficacy.
INTRODUCTION:Ulcerative colitis (UC) is an inflammatory bowel disease with a relapsing- remitting course, whose etiology is still unknown. Mild forms are generally managed with mesalazine, whereas moderate-to-severe disease may be addressed through a stepwise approach, often starting with corticosteroids and immunomodulators, and, when needed, progressing to advanced therapies targeting specific molecular pathways. Even though these therapies have led to substantial improvements in patients' quality of life and prognosis over recent decades, consistent and lasting therapeutic responses remain challenging to attain. AREAS COVERED:This review aims to outline emerging small molecules for UC, emphasizing efficacy and safety data from recent phase II-III clinical trials, including both published studies and ongoing research. We performed a thorough literature search using PubMed, Scopus, and ClinicalTrials.gov, excluding earlier-phase studies, and identified additional relevant articles through reference screening. EXPERT OPINION:It is essential to investigate innovative, safe, and easy-to-administer therapies that target alternative immunological pathways to enhance UC treatment. Some molecules, such as miRNA-124 upregulators, JAKi, S1P modulators, and LANCL2 agonists, may enrich our therapeutic armamentarium in UC management. To further optimize therapeutic strategies, combining small molecules with biologic agents could enhance treatment effectiveness, reduce immunogenicity, and improve long-term durability by targeting complementary inflammatory pathways.
INTRODUCTION:The tight junction protein Claudin-18.2 (CLDN-18.2) has been identified as a novel drug target for various solid tumors, including biliary tract cancers (BTC). Antibody-based approaches to target CLDN-18.2 have shown promising results in early clinical trials and several novel modalities like antibody-drug conjugates, bispecific T-cell engagers or CAR T-cells are currently also explored. AREAS COVERED:This review discusses the translational knowledge and gaps related to the underrepresentation of BTC in early clinical (basket) studies. We outline the current status of early clinical trials of drugs targeting CLDN-18.2 in BTC and discuss the need to determine prevalence and cutoff data in larger cohorts to overcome limitations related to clinical and molecular heterogeneity of BTC. EXPERT OPINION:Targeting CLDN-18.2 is a promising novel approach to treat solid tumors, including BTC. To confirm encouraging first clinical data, larger studies specific for BTC are needed to address tumor heterogeneity and to determine cutoff levels of CLDN-18.2 expression. Such studies are also needed to understand combination options and sequencing of therapies and to further validate novel approaches to fully exploit the potential of targeting CLDN-18.2 in BTC.
INTRODUCTION:Focal epilepsy is a leading cause of neurological disability, with about one-third of patients failing to achieve seizure freedom despite numerous antiseizure medications (ASMs) are available. Most current therapies broadly modulate synaptic transmission, leading to dose-limiting cognitive, psychiatric, and systemic adverse effects. Kv7 (KCNQ) potassium channels, responsible for the neuronal M-current, represent a high-precision therapeutic target that regulates intrinsic excitability and provides a fundamental 'molecular brake' against pathological firing. AREAS COVERED:This mini-review summarizes the clinical evolution of Kv7 modulation, from the first-generation prototype ezogabine to more selective second-generation candidates. We outline the scientific rationale for targeting the M-current, review emerging clinical data for agents such as azetukalner (XEN1101) and opakalim (BHV-7000), and highlight preclinical strategies including dual-mechanism modulators and drug repurposing. EXPERT OPINION:Kv7 agonists offer a mechanistically elegant approach to restoring seizure resistance. Second-generation agents provide encouraging mechanistic and clinical proof-of-concept, but long-term success will depend on clear advantages in patient-centered outcomes over established ASMs. Future value is likely to lie in precision-medicine strategies for KCNQ2/3-related encephalopathies and a carefully defined role in managing neuropsychiatric comorbidities.
INTRODUCTION:Neovascular age-related macular degeneration (nAMD), or wet AMD, remains a leading cause of vision loss in older adults. Current standard of care relies on repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, which create significant treatment burdens for patients and healthcare systems. Emerging gene therapies aim to address these challenges by delivering sustained therapeutic effects via single administration. AREAS COVERED:Next-generation gene therapies are transforming AMD treatment by enabling sustained, autonomous production of therapeutic proteins within ocular tissues, enabling the eye to synthesize its own anti-VEGF agents. A comprehensive literature search was performed using both PubMed and ClinicalTrials.gov to identify pertinent manuscripts and clinical trials for this narrative review. Keywords utilized included: Gene therapy, wet AMD, neovascular AMD, Viral Vectors, Adeno-associated viral vectors, Subretinal, Suprachoroidal, and Retinal Pigment Epithelium. EXPERT OPINION:Advances in gene therapy for wet AMD may revolutionize treatment by enabling sustained intraocular anti-VEGF protein, reducing frequent injections, improving patient adherence, and potentially lowering long-term healthcare costs. Although promising, challenges including long-term safety, complex delivery procedures, immune responses, regulatory hurdles, and the need for optimized vectors and clinical protocols must be addressed before widespread adoption and integration into standard care.
INTRODUCTION:Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobinopathy that causes significant morbidity and mortality in children and adults. The availability of novel therapeutic agents that are safe, effective, and affordable and new cell therapy techniques remains highly desirable for the treatment of SCD. AREAS COVERED:After a brief reminder of the main SCD complications, this review summarizes emerging disease-modifying agents and promising cell therapy strategies for the treatment of patients with SCD. A comprehensive search to look for the efficacy and safety of new agents was made on PubMed.ncbi.nlm.nih.gov for published studies and ClinicalTrials.gov for registered trials. EXPERT OPINION:The landscape of therapy in patients with SCD has recently moved toward more personalized therapeutic approaches. Promising preliminary data were obtained with some disease-modifying agents and gene therapies became available and promising for curing patients. However, the high cost remains a major limiting factor for these new therapies, which are far from being used in all patients, even in the more developed countries. Hydroxyurea is still regarded as the best disease-modifying treatment for SCD and allogeneic hematopoietic stem cell transplantation as the standard 'curative' therapy. Continued research is still warranted to sustain therapeutic advancements and development in SCD.
INTRODUCTION:Obesity and cancer cachexia represent two seemingly contrasting yet interrelated ends of the metabolic disorder spectrum, both characterized by disrupted energy homeostasis, inflammation and neuroendocrine dysfunction, and associated with increased morbidity and mortality. Existing treatments often fail to address the complex underlying pathophysiological mechanisms. Emerging research highlights the role of the gut microbiome in the pathophysiology of both conditions and how it can serve as a novel therapeutic target. AREAS COVERED:This review explores shared and distinct pathways linking obesity and cancer cachexia. Key systems discussed include the gut-brain axis as well as skeletal muscle and adipose tissue metabolism. We discuss how the gut microbiota influences these processes through (diet-derived) gut microbial metabolites that affect specific signaling pathways. The review evaluates the efficacy and limitations of current anti-obesity and cachexia therapies and summarizes clinical and preclinical interventions targeting the gut microbiome, including pre-, pro-, postbiotics and fecal microbiota transplantation. EXPERT OPINION:The gut microbiota holds potential as a therapeutic target in metabolic diseases, offering opportunities for precision medicine based on microbial and metabolic profiles. While early microbiota-based therapies show promise, further investigation into mechanistic pathways and novel engineered microbiota is essential to develop effective treatments for obesity and cachexia.
INTRODUCTION:Glaucoma is a progressive optic neuropathy with medical therapies historically focusing on topical administration of drops. Thus, large barriers to effective treatment exist, including poor medication adherence and intolerance to local adverse effects. Emerging therapies are targeted toward circumventing some of these challenges and are now focused on newer topical formulations, sustained-release implants, and more recently gene therapy. AREAS COVERED:This review is intended to cover the existing and emerging medical therapies for glaucoma. It includes literature from searches from PubMed, published abstracts as well as press releases and company communications. Included articles were published from 1954 to 2025. EXPERT OPINION:Several new medical therapies for glaucoma are currently in development. Emerging pharmacological and drug delivery methods have the potential to provide longer-lasting therapeutic and potentially preventative treatments for individuals with glaucoma. Further investigation is needed to determine the long-term clinical implications of such treatments for glaucoma.
INTRODUCTION:Immune thrombocytopenia (ITP) is an autoimmune disorder leading to low platelet counts and increased bleeding risk. The management of ITP, particularly in chronic or refractory cases, presents ongoing challenges, necessitating the development of novel therapeutic approaches that target its complex immunopathophysiology. AREAS COVERED:This review evaluates the current ITP treatment landscape, including established first-line and second-line therapies, and provides an in-depth analysis of emerging drug classes. Key areas include neonatal Fc receptor inhibitors, Bruton's tyrosine kinase inhibitors, spleen tyrosine kinase inhibitors, complement inhibitors, and novel immunotherapies. The scientific rationale, clinical trial data, efficacy, safety profiles, and potential positioning of these agents in future ITP management algorithms are discussed. The literature search encompassed PubMed, Embase, and clinical trial registries for articles and data published up to early 2025. EXPERT OPINION:Therapeutic options for ITP are rapidly expanding beyond conventional immunosuppressants and splenectomy. Emerging targeted therapies offer the promise of improved efficacy, better safety profiles, and the potential for durable, treatment-free remission. Future research should focus on personalized medicine approaches, biomarker identification for predicting treatment response, optimizing treatment sequencing, and understanding long-term outcomes to transform ITP care.
INTRODUCTION:The treatment armamentarium for multiple myeloma (MM) has evolved substantially over the past 20 years. Standard-of-care regimens for newly diagnosed MM and early relapsed/refractory disease (RRMM) include quadruplets and triplets comprising CD38 monoclonal antibodies, proteasome inhibitors, and/or immunomodulatory drugs, plus dexamethasone. Targeted agents and immune-based therapies are being used increasingly early in the treatment algorithm. There is an ongoing need for novel treatment options to improve outcomes with existing therapies and in subsequent lines of treatment. AREAS COVERED:We review preclinical/clinical data on the cereblon E3 ligase modulator mezigdomide, which is in phase 3 investigation in RRMM. We searched the published literature using PubMed, plus congress abstracts from the past 5 years and current records on ClinicalTrials.gov, using the terms 'mezigdomide' or 'CC-92480' and 'myeloma.' EXPERT OPINION:Mezigdomide, which is not currently approved for the treatment of MM, has higher cereblon binding affinity and greater potency for substrate protein degradation than the immunomodulatory drugs, and this is translating into notable clinical efficacy in early-phase trials, including in poor-prognosis settings such as triple-class-refractory disease. It has shown synergistic effects in preclinical studies with standard-of-care therapies and is being evaluated clinically in various combinations, including with/following T-cell engaging therapies for RRMM.
