Expert Opinion on Emerging Drugs最新文献

{"title":"Status of current trials and potential future trials with sparsentan.","authors":"Howard Trachtman, Radko Komers, 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}

{"title":"Potential use of psilocybin drugs in the treatment of depression.","authors":"Katarzyna Śladowska, Paweł Kawalec, Tomasz Brzostek, Andrzej Pilc","doi":"10.1080/14728214.2023.2264180","DOIUrl":"10.1080/14728214.2023.2264180","url":null,"abstract":"<p><strong>Introduction: </strong>Depression is a common disabling psychiatric disorder, which - in extreme cases - may lead to suicide if untreated or inadequately treated. Despite the availability of various treatments for depression, including pharmacotherapy, there is still a need to search for new agents with higher effectiveness and faster onset of action, especially for patients with treatment-resistant depression.</p><p><strong>Areas covered: </strong>A substance that has attracted considerable attention for nearly a decade is psilocybin, a natural psychedelic found in psilocybin mushrooms. In this study, we evaluated the efficacy and safety of psilocybin in the treatment of depression, based on pivotal randomized clinical trials. Moreover, we used findings from observational studies regarding recreational use. We also looked at ongoing clinical trials and discussed the registration status and clinical potential of the drug.</p><p><strong>Expert opinion: </strong>Clinical phase I-II trials published to date reported promising results for psilocybin in the treatment of patients with major depressive disorder and treatment-resistant depression, in a relatively short time after administration. However, before psilocybin is approved for use and administered to patients with depression, the results of large ongoing phase III clinical trials are needed to confirm its efficacy and safety and to change the way it is perceived by physicians and patients.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"241-256"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41196197","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":"Apomorphine for Parkinson's disease: pharmacologic and clinical considerations.","authors":"Maxwell J Wagner, Charles P Daniel, Connor J Plaisance, Grant E Borne, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D Kaye","doi":"10.1080/14728214.2023.2278677","DOIUrl":"10.1080/14728214.2023.2278677","url":null,"abstract":"<p><strong>Introduction: </strong>In Parkinson's disease, dopamine depletion in the basal ganglia leads to symptoms including bradykinesia, gait abnormalities, and cognitive impairment. Even with treatment, the disease course leads to decreases in the amount of dopamine produced and released into the synapse. As dopamine production falls and the treatment course is insufficient to match the metabolic supply and demand, acute 'off' periods develop that cause reemergence of symptoms. Apomorphine is used to reverse these 'off' periods and restore function in patients with Parkinson's. This review will provide clinicians a concise article to read to learn more about apomorphine and its appropriate utilization.</p><p><strong>Areas covered: </strong>The research discussed is focused on the history, pharmacokinetics, and mechanism of action of Apomorphine. Its utilization as a treatment for Parkinson's Disease and its comparison to currently utilized drugs is also discussed in this review. We focused on articles published on PubMed and Google Scholar within the last 10 years, but in some instances had to go as far back as 1951 to include early articles published about apomorphine.</p><p><strong>Expert opinion: </strong>The expert opinion section focuses on the ways in which apomorphine could be administered in the future to better promote utilization and increase tolerability.</p>","PeriodicalId":12292,"journal":{"name":"Expert Opinion on Emerging Drugs","volume":" ","pages":"275-281"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422179","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}