Expert opinion on investigational drugs最新文献_第9页

Lessons learned from early-stage clinical trials for diabetic nephropathy. 从糖尿病肾病早期临床试验中汲取的教训。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-04-01 Epub Date: 2024-03-15 DOI: 10.1080/13543784.2024.2326025

Marc Rendell

{"title":"Lessons learned from early-stage clinical trials for diabetic nephropathy.","authors":"Marc Rendell","doi":"10.1080/13543784.2024.2326025","DOIUrl":"10.1080/13543784.2024.2326025","url":null,"abstract":"Introduction: The evolution of treatment for diabetic nephropathy illustrates how basic biochemistry and physiology have led to new agents such as SGLT2 inhibitors and mineralocorticoid blockers. Conversely, clinical studies performed with these agents have suggested new concepts for investigational drug development. We reviewed currently available treatments for diabetic nephropathy and then analyzed early clinical trials of new agents to assess the potential for future treatment modalities.Areas covered: We searched ClinicalTrials.gov for new agents under study for diabetic nephropathy in the past decade. Once we have identified investigation trials of new agents, we then used search engines and Pubmed.gov to find publications providing insight on these drugs. Current treatments have shown benefit in both cardiac and renal disease. In our review, we found 51 trials and 43 pharmaceuticals in a number of drug classes: mineralocorticoid blockers, anti-inflammatory, anti-fibrosis, nitric oxide stimulatory, and podocyte protection, and endothelin inhibitors.Expert opinion: It is difficult to predict which early phase treatments will advance to confirmatory clinical trials. Current agents are thought to improve hemodynamic function. However, the coincident benefit of both myocardial function and the glomerulus argues for primary effects at the subcellular level, and we follow the evolution of agents which modify fundamental cellular processes.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"287-301"},"PeriodicalIF":6.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Duchenne muscular dystrophy: promising early-stage clinical trials to watch. 杜兴氏肌肉萎缩症：值得关注的有希望的早期临床试验。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-06 DOI: 10.1080/13543784.2024.2313105

Annie Tang, Toshifumi Yokota

{"title":"Duchenne muscular dystrophy: promising early-stage clinical trials to watch.","authors":"Annie Tang, Toshifumi Yokota","doi":"10.1080/13543784.2024.2313105","DOIUrl":"10.1080/13543784.2024.2313105","url":null,"abstract":"Introduction: Current therapies are unable to cure Duchenne muscular dystrophy (DMD), a severe and common form of muscular dystrophy, and instead aim to delay disease progression. Several treatments currently in phase I trials could increase the number of therapeutic options available to patients.Areas covered: This review aims to provide an overview of current treatments undergoing or having recently undergone early-stage trials. Several exon-skipping and gene therapy approaches are currently being investigated at the clinical stage to address an unmet need for DMD treatments. This article also covers Phase I trials from the last 5 years that involve inhibitors, small molecules, a purified synthetic flavanol, a cell-based therapy, and repurposed cardiac or tumor medications.Expert opinion: With antisense oligonucleotide (AON) treatments making up the majority of conditionally approved DMD therapies, most of the clinical trials occurring within the last 5 years have also evaluated exon-skipping AONs. The approval of Elevidys, a micro-dystrophin therapy, is reflected in a recent trend toward gene transfer therapies in phase I DMD clinical trials, but their safety and efficacy are being established in this phase of development. Other Phase I clinical-stage approaches are diverse, but have a range in efficacy, safety, and endpoint measures.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"201-217"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deterministic reprogramming and signaling activation following targeted therapy in non-small cell lung cancer driven by mutations or oncogenic fusions. 突变或致癌融合驱动的非小细胞肺癌靶向治疗后的确定性重编程和信号激活。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1080/13543784.2024.2320710

Rafael Rosell, Carlos Pedraz-Valdunciel, Anisha Jain, Chandan Shivamallu, Andrés Aguilar

{"title":"Deterministic reprogramming and signaling activation following targeted therapy in non-small cell lung cancer driven by mutations or oncogenic fusions.","authors":"Rafael Rosell, Carlos Pedraz-Valdunciel, Anisha Jain, Chandan Shivamallu, Andrés Aguilar","doi":"10.1080/13543784.2024.2320710","DOIUrl":"10.1080/13543784.2024.2320710","url":null,"abstract":"Introduction: Targeted therapy is used to treat lung adenocarcinoma caused by epidermal growth factor receptor (EGFR) mutations in the tyrosine kinase domain and rare subtypes (<5%) of non-small cell lung cancer. These subtypes include fusion oncoproteins like anaplastic lymphoma kinase (ALK), ROS1, rearranged during transfection (RET), and other receptor tyrosine kinases (RTKs). The use of diverse selective oral inhibitors, including those targeting rat sarcoma viral oncogene homolog (KRAS) mutations, has significantly improved clinical responses, extending progression-free and overall survival.Areas covered: Resistance remains a critical issue in lung adenocarcinoma, notably in EGFR mutant, echinoderm microtubule associated protein-like 4 (EML4)-ALK fusion, and KRAS mutant tumors, often associated with epithelial-to-mesenchymal transition (EMT).Expert opinion: Despite advancements in next generation EGFR inhibitors and EML4-ALK therapies with enhanced brain penetrance and identifying resistance mutations, overcoming resistance has not been abated. Various strategies are being explored to overcome this issue to achieve prolonged cancer remission and delay resistance. Targeting yes-associated protein (YAP) and the mechanisms associated with YAP activation through Hippo-dependent or independent pathways, is desirable. Additionally, the exploration of liquid-liquid phase separation in fusion oncoproteins forming condensates in the cytoplasm for oncogenic signaling is a promising field for the development of new treatments.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"171-182"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. 治疗胃肠道间质瘤的 KIT/PDGFRA 抑制剂：抓住问题的要害。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-14 DOI: 10.1080/13543784.2024.2318317

Carlo María Cicala, Iván Olivares-Rivas, Jon Ander Aguirre-Carrillo, César Serrano

{"title":"KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem.","authors":"Carlo María Cicala, Iván Olivares-Rivas, Jon Ander Aguirre-Carrillo, César Serrano","doi":"10.1080/13543784.2024.2318317","DOIUrl":"10.1080/13543784.2024.2318317","url":null,"abstract":"Introduction: Approximately 90% of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in receptor tyrosine-kinases KIT or PDGFRA. Despite the outstanding results of first-line imatinib in advanced GIST, resistance ultimately occurs mainly through secondary mutations in KIT/PDGFRA. Other tyrosine-kinase inhibitors (TKIs) with a broader spectrum of activity against these mutations are approved after imatinib failure. However, response rates and progression-free survival are drastically lower compared to imatinib. Notably, imatinib also triggers early tolerance adaptation mechanisms, which precede the occurrence of secondary mutations.Areas covered: In this review, we outline the current landscape of KIT inhibitors, discuss the novel agents, and present additional biological pathways that may be therapeutically exploitable.Expert opinion: The development of broad-spectrum and highly selective TKIs able to induce a sustained KIT/PDGFRA inhibition is the pillar of preclinical and clinical investigation in GIST. However, it is now recognized that the situation is more intricate, with various factors interacting with KIT and PDGFRA, playing a crucial role in the response and resistance to treatments. Future strategies in the management of advanced GIST should integrate driver inhibition with the blockade of other molecules to enhance cell death and establish enduring responses in patients.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"159-170"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drugs of the future for diarrhea-predominant irritable bowel syndrome: an overview of current investigational drugs. 治疗以腹泻为主的肠易激综合征的未来药物：当前在研药物概览。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1080/13543784.2024.2320703

Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi

{"title":"Drugs of the future for diarrhea-predominant irritable bowel syndrome: an overview of current investigational drugs.","authors":"Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi","doi":"10.1080/13543784.2024.2320703","DOIUrl":"10.1080/13543784.2024.2320703","url":null,"abstract":"Introduction: Irritable bowel syndrome (IBS) has a significant impact on society and quality of life. Current treatments are ineffective, and new investigational drugs are necessary.Areas covered: Numerous potential therapies are developing, targeting different areas such as cannabinoid signaling, opioid receptors, tachykinin (NK2) receptors, β3-adrenergic receptors, intestinal microbiota, inflammation, and 5HT receptors. Clinical trial evidence has shown that loperamide, eluxadoline, alosetron, ramosetron, bile acid sequestrants, and rifaximin can modulate GI alterations and benefit patients with IBS-D. Among the potential therapies, ibodutant, ibudilast, blautix, BOS-589, solabegron, vibegron, olorinab, ebastine, and ORP-101 have demonstrated possible effects but remain confirmed.Expert opinion: Individuals with IBS-D require cost-effective treatment options that do not impede their productivity or that of their caregivers. This is necessary for consistent healthcare and improved quality of life. Therefore, we should focus on developing new, efficient, and affordable medications for IBS-D. The government, insurers, and society must recognize this need and collaborate to ensure its fulfillment.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"219-228"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates. 治疗 2 型糖尿病的 GPR119 激动剂：临床前和早期候选药物过去的失败和未来的希望。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1080/13543784.2024.2321271

Deanne H Hryciw, Rhiannon K Patten, Raymond J Rodgers, Joseph Proietto, Dana S Hutchinson, Andrew J McAinch

{"title":"GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates.","authors":"Deanne H Hryciw, Rhiannon K Patten, Raymond J Rodgers, Joseph Proietto, Dana S Hutchinson, Andrew J McAinch","doi":"10.1080/13543784.2024.2321271","DOIUrl":"10.1080/13543784.2024.2321271","url":null,"abstract":"Introduction: Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the β-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic.Areas covered: This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D.Expert opinion: GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"183-190"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune checkpoint modulators in early clinical development for the treatment of type 1 diabetes 用于治疗 1 型糖尿病的早期临床开发免疫检查点调节剂

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 DOI: 10.1080/13543784.2024.2326036

Ernesto Maddaloni, Rocco Amendolara, Angela Balena, Alessandro Latino, Rosario Luigi Sessa, Raffaella Buzzetti

引用次数: 0

Enhancing anti-CD274 (PD-L1) targeting through combinatorial immunotherapy with bispecific antibodies and fusion proteins: from preclinical to phase II clinical trials. 通过双特异性抗体和融合蛋白的组合免疫疗法增强抗CD274（PD-L1）靶向性：从临床前到II期临床试验。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1080/13543784.2024.2319317

Dominik Kiem, Matthias Ocker, Richard Greil, Daniel Neureiter, Thomas Melchardt

{"title":"Enhancing anti-CD274 (PD-L1) targeting through combinatorial immunotherapy with bispecific antibodies and fusion proteins: from preclinical to phase II clinical trials.","authors":"Dominik Kiem, Matthias Ocker, Richard Greil, Daniel Neureiter, Thomas Melchardt","doi":"10.1080/13543784.2024.2319317","DOIUrl":"10.1080/13543784.2024.2319317","url":null,"abstract":"Introduction: Immune checkpoint inhibitors have achieved great success in the treatment of many different types of cancer. Programmed cell death protein ligand 1 (PD-L1, CD274) is a major immunosuppressive immune checkpoint and a target for several already approved monoclonal antibodies. Despite this, novel strategies are under development, as the overall response remains low.Areas covered: In this review, an overview of the current biomarkers for response to PD-L1 inhibitor treatment is given, followed by a discussion of potential novel biomarkers, including tumor mutational burden and circulating tumor DNA. Combinatorial immunotherapy is a potential novel strategy to increase the response to PD-L1 inhibitor treatment and currently, several interesting bispecific antibodies as well as bispecific fusion proteins are undergoing early clinical investigation. We focus on substances targeting PD-L1 and a secondary target, and a secondary immunomodulatory target like CTLA-4, TIGIT, or CD47.Expert opinion: Overall, the presented studies show anti-tumor activity of these combinatorial immunotherapeutic approaches. However, still relatively low response rates suggest a need for better biomarkers.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"229-242"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigational pharmacological agents for the treatment of ARDS. 用于治疗 ARDS 的试验性药物。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-27 DOI: 10.1080/13543784.2024.2315128

Katyayini Aribindi, Michelle Lim, Satyan Lakshminrusimha, Timothy Albertson

{"title":"Investigational pharmacological agents for the treatment of ARDS.","authors":"Katyayini Aribindi, Michelle Lim, Satyan Lakshminrusimha, Timothy Albertson","doi":"10.1080/13543784.2024.2315128","DOIUrl":"10.1080/13543784.2024.2315128","url":null,"abstract":"Introduction: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID-related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research.Areas covered: The aim of this review is to discuss adjuvant pharmacotherapies targeting non-COVID Acute Lung Injury (ALI)/ARDS and novel therapeutics in COVID associated ALI/ARDS. In ARDS, variable data may support selective use of neuromuscular blocking agents, corticosteroids and neutrophil elastase inhibitors, but are not yet universally used. COVID-ALI/ARDS has data supporting the use of IL-6 monoclonal antibodies, corticosteroids, and JAK inhibitor therapy.Expert opinion: Although ALI/ARDS modifying pharmacological agents have been identified in COVID-related disease, the data in non-COVID ALI/ARDS has been less compelling. The increased use of more specific molecular phenotyping based on physiologic parameters and biomarkers, will ensure equipoise between groups, and will likely allow more precision in confirming pharmacological agent efficacy in future studies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"243-277"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies. 治疗血管性水肿的 Kallikrein 抑制剂：临床前和早期阶段研究的进展。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-26 DOI: 10.1080/13543784.2024.2320700

Henriette Farkas, Zsuzsanna Balla

{"title":"Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies.","authors":"Henriette Farkas, Zsuzsanna Balla","doi":"10.1080/13543784.2024.2320700","DOIUrl":"10.1080/13543784.2024.2320700","url":null,"abstract":"Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema and predominantly caused by the dysregulation of the kinin-kallikrein system.Areas covered: This manuscript presents the results of preclinical and early clinical trials of newer drugs targeting the dysregulated kinin-kallikrein system. ATN-249 is an oral drug that has shown promising results in preclinical and Phase I studies, and good tolerability in the prophylactic treatment of attacks. KVD900 is also an oral agent developed for the on-demand treatment of HAE attacks. It has shown positive results in Phase I/II studies, with rapid absorption. The third drug, IONIS-PKKRx, is an antisense oligonucleotide targeting plasma prekallikrein mRNA. It has shown a dose-dependent reduction of plasma prekallikrein levels and proenzyme activation in Phase I/II studies, and has shown promising results. STAR-0215 is a long acting anti-activated kallikrein monoclonal antibody. A Phase 1a single ascending dose trial evaluated its safety, pharmacokinetics, and pharmacodynamics. Lastly, NTLA-2002 is an investigational gene-editing therapy.Expert opinion: The targeted treatment of the dysregulated kinin-kallikrein system with specific inhibitors is promising for the prevention of angioedema attacks. Ongoing phase III studies will provide further insight into the efficacy and long-term safety of these novel therapies, potentially expanding treatment options for HAE treatment.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"191-200"},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0