Expert Opinion on Emerging Drugs最新文献

{"title":"Systemic mastocytosis: 2023 update on diagnosis and management in adults.","authors":"Alessandro Costa,&nbsp;Emilia Scalzulli,&nbsp;Ida Carmosino,&nbsp;Marcello Capriata,&nbsp;Claudia Ielo,&nbsp;Chiara Masucci,&nbsp;Mauro Passucci,&nbsp;Maurizio Martelli,&nbsp;Massimo Breccia","doi":"10.1080/14728214.2023.2221028","DOIUrl":"10.1080/14728214.2023.2221028","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.</p><p><strong>Areas covered: </strong>The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib.</p><p><strong>Expert opinion: </strong>Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"153-165"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging drugs for dementia with Lewy Bodies: a review of Phase II & III trials.","authors":"Magdalena I Tolea,&nbsp;Reem Ezzeddine,&nbsp;Simone Camacho,&nbsp;James E Galvin","doi":"10.1080/14728214.2023.2244425","DOIUrl":"10.1080/14728214.2023.2244425","url":null,"abstract":"<p><strong>Introduction: </strong>Despite faster cognitive decline and greater negative impact on patients and family caregivers, drug development efforts in Dementia with Lewy Bodies (DLB) fall behind those for Alzheimer's Disease (AD). Current off-label drug DLB treatment options are limited to symptomatic agents developed to address cognitive deficits in AD, motor deficits in Parkinson's Disease, or behavioral symptoms in psychiatric disease. Aided by recent improvements in DLB diagnosis, a new focus on the development of disease-modifying agents (DMA) is emerging.</p><p><strong>Areas covered: </strong>Driven by evidence supporting different pathological mechanisms in DLB and PDD, this review assesses the evidence on symptomatic drug treatments and describes current efforts in DMA development in DLB. Specifically, our goals were to: (1) review evidence supporting the use of symptomatic drug treatments in DLB; (2) review the current DMA pipeline in DLB with a focus on Phase II and III clinical trials; and (3) identify potential issues with the development of DMA in DLB. Included in this review were completed and ongoing drug clinical trials in DLB registered on ClinicalTrials.gov (no time limits set for the search) or disseminated at the 2023 international conference on Clinical Trials in AD. Drug clinical trials registered in non-US clinical trial registries were not included.</p><p><strong>Expert opinion: </strong>Adoption of current symptomatic drug treatments used off-label in DLB relied on efficacy of benefits in other disorders rather than evidence from randomized controlled clinical trials. Symptoms remain difficult to manage. Several DMA drugs are currently being evaluated as either repurposing candidates or novel small molecules. Continued improvement in methodological aspects including development of DLB-specific outcome measures and biomarkers is needed to move the field of DMA drug development forward.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"167-180"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Status of current trials and potential future trials with sparsentan.","authors":"Howard Trachtman,&nbsp;Radko Komers,&nbsp;Jula Inrig","doi":"10.1080/14728214.2023.2239151","DOIUrl":"10.1080/14728214.2023.2239151","url":null,"abstract":"This editorial summarizes the scientific rationale for the use of sparsentan in proteinuric kidney disease. It reviews the ongoing randomized clinical trials of the drug in IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) as well as studies in pediatric patients and outlines the potential role of sparsentan in the future management of patients with proteinuric kidney disease. There is abundant evidence supporting the role of angiotensin II (AngII) and endothelin-1 (ET-1) signaling in the pathogenesis and perpetuation of glomerular injury. These vasoactive molecules act on mesangial and endothelial cells and podocytes, causing a variety of pathological changes in glomeruli, leading to proteinuria, and ultimately progressive glomerulosclerosis. Moreover, these signaling cascades interact with one another underscoring the potential application of sparsentan, a novel non-immunosuppressive dual endothelin and angiotensin receptor antagonist (DEARA) that blocks AT1 and Endothelin Type A (ETA) receptor activation The preclinical and clinical evidence supporting the use of dual AT1/ETA receptor inhibition over monoblockers of AngII or ET-1 actions in the treatment of kidney diseases has been reviewed by Komers and Plotkin [1]. Recent findings reinforce the value of specifically inhibiting ET-1 in patients with glomerular disease. Endothelin gene expression is elevated in patients with glomerular disease such as IgA nephropathy and an increased risk of disease progression [2]. Preclinical studies with sparsentan demonstrated a spectrum of antiproliferative, anti-inflammatory, antifibrotic, and podocyteprotective actions of the drug in different models of kidney disease including FSGS, IgAN, and Alport syndrome [3–6]. A novel protective mechanism of sparsentan in FSGS was recently suggested by Li et al. [7]. The abundance of tissueresident lymphocytes and the proportion of CD8 TRM cells are increased in kidneys from patients with FSGS. Sparsentan reduced TRM cell responses by inhibiting Ang II and/or ET1-mediated IL-15 signaling, thereby further regulating renal CD8 TRM cell accumulation in the kidney [5]. ETA receptor expression is increased in kidney biopsy specimens obtained from patients with FSGS, and the intensity is directly related to nephron loss and oxidative damage. The degree of oxidative stress is, in turn, associated with proteinuria [8,9]. 2. Sparsentan in IgA nephropathy (IgAN) and PROTECT","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"145-147"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging immunotherapeutic strategies for cutaneous lupus erythematosus: an overview of recent phase 2 and 3 clinical trials.","authors":"Darosa Lim, Julianne Kleitsch, Victoria P Werth","doi":"10.1080/14728214.2023.2273536","DOIUrl":"10.1080/14728214.2023.2273536","url":null,"abstract":"<p><strong>Introduction: </strong>Cutaneous lupus erythematosus (CLE) is an autoimmune disease that is clinically heterogenous and may occur with or without the presence of systemic lupus erythematosus (SLE). While existing on a spectrum, CLE and SLE present differences in their underlying pathogenesis and therapeutic responses. No new therapies have been approved in recent decades by the U.S. Food and Drug Administration for CLE, although frequently refractory to conventional therapies. There is an unmet need to develop effective drugs for CLE as it significantly impacts patients' quality of life and may leave irreversible disfiguring damage.</p><p><strong>Areas covered: </strong>This review provides an update on the latest phase 2 and 3 clinical trials performed in CLE or SLE using skin-specific outcome measures. Emergent therapies are presented alongside their mechanism of action as recent translational studies have permitted identification of critical targets among immune cells and/or pathways involved in CLE.</p><p><strong>Expert opinion: </strong>While the recent literature has few trials for CLE, drugs targeting type I interferon, its downstream signaling and plasmacytoid dendritic cells have shown promising results. Further research is required to develop long-awaited effective therapies, and this review highlights the importance of implementing trials dedicated to CLE to fill the current gap in CLE therapeutics.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"257-273"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is clinical trial data showing positive progress for the treatment of diabetic kidney disease?","authors":"Seng Kiong Tan, Mark E Cooper","doi":"10.1080/14728214.2023.2277762","DOIUrl":"10.1080/14728214.2023.2277762","url":null,"abstract":"","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"217-226"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What's new on the horizon for polycystic ovarian syndrome? Exploring emerging drugs in phase II.","authors":"Giuseppe D'Angelo,&nbsp;Mario Ascione,&nbsp;Ilaria Morra,&nbsp;Paolo Verrazzo,&nbsp;Giuseppe Bifulco,&nbsp;Pierluigi Giampaolino,&nbsp;Luigi Della Corte","doi":"10.1080/14728214.2023.2260746","DOIUrl":"10.1080/14728214.2023.2260746","url":null,"abstract":"Polycystic Ovarian Syndrome (PCOS) affects millions of women globally, and, depending on the diagnostic criteria used, PCOS has an estimated prevalence of between 7% to 17% of reproductive-aged women causing a range of symptoms such as irregular menstrual cycles, excessive hair growth, weight gain, and infertility [1]. PCOS is characterized by a complex interplay of hormonal, metabolic, and reproductive disturbances. The syndrome’s underlying changes impact multiple systems, leading to several and complex clinical manifestations. One of the hallmark features of PCOS is hyperandrogenism which brings on symptoms like excessive hair growth, acne and alopecia. Anovulation and irregular menstrual cycles stem from the imbalance in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) triggered by androgen fluctuations. PCOS often involves both hyperandrogenism and insulin resistance, due to reduced sensitivity of target cells. These metabolic conditions over time lead to increased risk of type 2 diabetes, obesity, and dyslipidemia development. The interplay between insulin resistance and hyperandrogenism intensifies the syndrome’s clinical symptoms. Abnormal gonadotropin-releasing hormone (GnRH) secretion has consequences of ovarian anovulation and cyst formation, resulting in unbalanced FSH and LH production.","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"149-152"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41118997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer drugs with high repositioning potential for Alzheimer's disease.","authors":"Jad Majeed, Marwan N Sabbagh, Min H Kang, J Josh Lawrence, Kevin Pruitt, Sarah Bacus, Ellie Reyna, Maddy Brown, Boris Decourt","doi":"10.1080/14728214.2023.2296079","DOIUrl":"10.1080/14728214.2023.2296079","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan.</p><p><strong>Areas covered: </strong>Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies.</p><p><strong>Expert opinion: </strong>Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"311-332"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on emerging drugs for the treatment of idiopathic pulmonary fibrosis: a look towards 2023 and beyond.","authors":"Carmelo Sofia, Alessia Comes, Giacomo Sgalla, Luca Richeldi","doi":"10.1080/14728214.2023.2281416","DOIUrl":"10.1080/14728214.2023.2281416","url":null,"abstract":"<p><strong>Introduction: </strong>Currently approved drug treatments for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, have been shown to slow lung function decline and improve clinical outcomes. Since significant advances in the understanding of pathogenetic mechanisms in IPF, novel potential agents are being tested to identify new targeted and better tolerated therapeutic strategies.</p><p><strong>Areas covered: </strong>This review describes the evidence from IPF phase II and III clinical trials that have been completed or are ongoing in recent years. The literature search was performed using Medline and Clinicaltrials.org databases. Particular attention is paid to the new inhibitor of phosphodiesterase 4B (BI 1015550), being studied in a more advanced research phase. Some emerging critical issues of the pharmacological research are highlighted considering the recent outstanding failures of several phase III trials.</p><p><strong>Expert opinion: </strong>An exponential number of randomized clinical trials are underway testing promising new molecules to increase treatment choices for patients with IPF and improve patients' quality of life. The next goals should aim at a deeper understanding of the pathogenic pathways of the disease with the challenging goal of being able not only to stabilize but also to reverse the ongoing fibrotic process in patients with IPF.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"283-296"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging synthetic drugs for the treatment of diffuse large B-cell lymphoma.","authors":"Ning Dong,&nbsp;Lucia Perez-Lamas,&nbsp;Julio C Chavez","doi":"10.1080/14728214.2023.2250722","DOIUrl":"10.1080/14728214.2023.2250722","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. Recent advances in immunotherapy such as chimeric antigen receptor T-cell therapy have significantly improved the outcomes in patients. Despite those advances, disease still recurs in many patients after multiple lines of therapy, and they eventually die. Many novel agents are under investigation. In this review, we focus on the synthetic drugs, usually small-molecule oral agents, that target a specific tumor-cell survival pathway.</p><p><strong>Areas covered: </strong>We discuss immunomodulatory drugs, cereblon E3 ligase modulators, Bruton tyrosine kinase degraders, B-cell lymphoma-2 inhibitors, Enhancer of Zeste 2 inhibitors, IRAK4 inhibitors/IRAK4 protein degraders, bromodomain and extraterminal inhibitors, cyclin-dependent kinase 9 inhibitors, and menin inhibitors. We focus on their mechanisms of action, activities in DLBCL, and, in some cases, toxicity. We also discuss the challenges in developing synthetic drugs in DLBCL.</p><p><strong>Expert opinion: </strong>Synthetic drugs hold great potential for treating DLBCL. Many phase 1/2 trials are ongoing. To maximize their clinical benefit, a better understanding of the biology of this heterogeneous group of diseases is needed, synergic combinations need to be identified, and the sequencing of therapies needs to be considered.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"181-190"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are clinical trials into emerging drugs for the treatment of alpha-1 antitrypsin deficiency providing promising results?","authors":"Joshua De Soyza, Anita Pye, Alice M Turner","doi":"10.1080/14728214.2023.2296088","DOIUrl":"10.1080/14728214.2023.2296088","url":null,"abstract":"","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"227-231"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}