Expert opinion on investigational drugs最新文献

Investigational treatments for cytomegalovirus infection in phase I and II study. 巨细胞病毒感染的I期和II期研究。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-21 DOI: 10.1080/13543784.2025.2579018

Morgan Hakki, Anat Stern, Genovefa A Papanicolaou

{"title":"Investigational treatments for cytomegalovirus infection in phase I and II study.","authors":"Morgan Hakki, Anat Stern, Genovefa A Papanicolaou","doi":"10.1080/13543784.2025.2579018","DOIUrl":"https://doi.org/10.1080/13543784.2025.2579018","url":null,"abstract":"Introduction: The additions of letermovir and maribavir to the cytomegalovirus (CMV) armamentarium have markedly changed the landscape of CMV prevention and treatment in transplant recipients. However, their currently approved indications remain relatively restricted, and there is still a definite need for additional interventions to limit the impact of CMV in both immunocompromised and immunocompetent persons. The development of novel antivirals, vaccines, and immunotherapy-based strategies would represent significant steps toward this goal.Areas covered: This review examines anti-CMV agents in early stage (Phase I or II) clinical trials, including expanding indications for existing agents, novel agents, vaccines, and immune-based therapies.Expert opinion: Despite recent advances in CMV chemoprevention and treatment in transplant recipients, there remains a need for a broader, more diversified approach to mitigating the impact of CMV infection in both transplant and non-immunocompromised persons. Intravenous brincidofovir would provide an important alternative option to current antivirals in the right clinical setting. Several promising vaccine candidates are in various stages of clinical development. A safe and effective vaccine may also expand preventative strategies beyond transplant recipients and into healthy persons, specifically for the prevention of maternal-to-fetal transmission. The therapeutic possibilities of VST and TCR therapy represent important potential adjuncts to antivirals.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336657","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

New investigational agents for the treatment of clostridioides difficile infections. 治疗艰难梭菌感染的新研究药物。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-21 DOI: 10.1080/13543784.2025.2579016

Mai-Chi N Tran, Taryn A Eubank, Ravina Kullar, Lynne V McFarland, Kevin W Garey, Ellie Jc Goldstein

{"title":"New investigational agents for the treatment of clostridioides difficile infections.","authors":"Mai-Chi N Tran, Taryn A Eubank, Ravina Kullar, Lynne V McFarland, Kevin W Garey, Ellie Jc Goldstein","doi":"10.1080/13543784.2025.2579016","DOIUrl":"https://doi.org/10.1080/13543784.2025.2579016","url":null,"abstract":"Introduction: The Centers for Disease Control and Prevention (CDC), estimates that Clostridioides difficile infection (CDI) results in 250,000 hospitalizations yearly in the U.S.A. an annual mortality of 12,800 and recurrence in 15-30% of patients. Consequently, new approaches and agents are needed to treat CDI. We review the current developmental pipeline for various categories of CDI therapies.Areascovered: We searched various data bases to identify relevant data.Expert opinion: Ibezapolstat, CRS3123, and ridinilazole were identified with unique mechanisms of action and narrow spectrums of activity that result in gut microbiome preservation and reduced recurrent CDI (rCDI) rates. One cannot predict the potential efficacy of these new agents under study until further studies are done. Some may emerge as only supplemental therapies, while others may fail or be shelved and hopefully at least one will emerge as a primary CDI therapy and to prevent rCDI. Some have the ability to restore the microbiome (VE303) or preserve intestinal integrity (e.g. REC-3964, LMN-201, AQ). Regardless, patients and clinicians need new agents. CDI is a significant burden to the healthcare system and the quality of life for patients who suffer from CDI and rCDI. Further development of these investigational agents to prevent this cycle are of upmost importance.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336696","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

IRAK signaling in cancers: mechanisms, targeting, and clinical implications. 癌症中的IRAK信号：机制、靶向和临床意义

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-15 DOI: 10.1080/13543784.2025.2573646

Eric J Vick, Daniel T Starczynowski

{"title":"IRAK signaling in cancers: mechanisms, targeting, and clinical implications.","authors":"Eric J Vick, Daniel T Starczynowski","doi":"10.1080/13543784.2025.2573646","DOIUrl":"10.1080/13543784.2025.2573646","url":null,"abstract":"Introduction: All human cells have the capacity to respond to damage or danger through conserved signaling pathways that converge on interleukin-1 receptor-associated kinases (IRAKs). IRAKs are a family of kinases that play central roles in innate immunity and inflammation and are increasingly implicated in the development and progression of cancer.Areas covered: IRAKs are tightly regulated by multiple mechanisms to prevent aberrant activation. Dysregulated IRAK function has been increasingly recognized for its role in cancer initiation, progression, and therapy resistance, extending beyond its canonical function in inflammatory signaling. While much of the research to date has focused on IRAK signaling in hematologic malignancies, emerging evidence suggests that IRAKs are also activated and therapeutically relevant in solid tumors. As a result, several small-molecule inhibitors targeting one or more IRAK family members are now approved, in clinical trials, or under preclinical development. In this review, we summarize the current understanding of IRAK biology in cancer, with a particular focus on therapeutic strategies and the translational potential of IRAK-targeted therapies.Expert opinion: IRAK inhibitors and degraders are promising treatments for a variety of cancers. Future clinical success will depend on optimizing kinase selectivity profiles and identifying biomarkers to guide patient selection and combination strategies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-18"},"PeriodicalIF":4.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274380","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

Androgen receptor pathway signaling inhibitors in development for prostate cancer therapy. 雄激素受体通路信号抑制剂在前列腺癌治疗中的应用。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-15 DOI: 10.1080/13543784.2025.2573647

Sara Bleve, Pier Vitale Nuzzo, Abdul Baseet Arham, Aaron Holmes, Scott T Tagawa

{"title":"Androgen receptor pathway signaling inhibitors in development for prostate cancer therapy.","authors":"Sara Bleve, Pier Vitale Nuzzo, Abdul Baseet Arham, Aaron Holmes, Scott T Tagawa","doi":"10.1080/13543784.2025.2573647","DOIUrl":"10.1080/13543784.2025.2573647","url":null,"abstract":"Introduction: Prostate cancer (PC), including castration-resistant disease (CRPC), remains largely driven by dysregulated androgen receptor (AR) signaling. While androgen deprivation therapy (ADT) combined with next-generation AR inhibitors improves survival, resistance inevitably arises through mechanisms such as AR amplification, mutations, and splice variants. Additionally, chronic AR suppression induces significant metabolic, musculoskeletal, and cardiovascular toxicities, highlighting the need for novel therapies that overcome resistance while minimizing systemic adverse effects.Areas covered: This review outlines the pivotal role of AR signaling in PC pathogenesis and evaluates the clinical impact and limitations of current AR-targeted therapies. In addition, it examines emerging therapeutic strategies aimed at modulating AR activity, disrupting androgen biosynthesis, and degrading the AR protein itself. Finally, we explore novel approaches targeting alternative oncogenic pathways involved in resistance and lineage plasticity, with the goal of advancing more effective and durable treatment paradigms.Expert opinion: Novel strategies such as bipolar androgen therapy (BAT), selective androgen receptor modulators (SARMs), and AR degraders like PROTACs offer context-specific or mechanistically distinct ways to overcome resistance to traditional AR antagonism in prostate cancer. These approaches, along with CYP11A1 inhibitors and resistance pathway targeting (e.g. PI3K/AKT, EZH2), mark a shift toward more personalized therapies aimed at improving efficacy while minimizing toxicity.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-19"},"PeriodicalIF":4.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250673","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

Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects. 新型选择性S1P1受体调节剂HE009的药代动力学、药效学和安全性研究

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-14 DOI: 10.1080/13543784.2025.2570244

Jie Ding, Qian Zhang, Qin Yang, Qin Zhang, Sihui Tu, Yangyang Zuo, Zhiwei Yao, Peng Deng, Lin Tao, Liang Zheng, Wei Hu

{"title":"Pharmacokinetics, pharmacodynamics, and safety of HE009, a novel selective S1P1 receptor modulator, in healthy Chinese subjects.","authors":"Jie Ding, Qian Zhang, Qin Yang, Qin Zhang, Sihui Tu, Yangyang Zuo, Zhiwei Yao, Peng Deng, Lin Tao, Liang Zheng, Wei Hu","doi":"10.1080/13543784.2025.2570244","DOIUrl":"10.1080/13543784.2025.2570244","url":null,"abstract":"Objective: HE009, a novel selective sphingosine-1-phosphate receptor-1 (S1P1) modulator, was evaluated in healthy Chinese subjects to assess its pharmacokinetics, pharmacodynamics, and safety profile.Research design and methods: This randomized, placebo-controlled phase I study comprised single ascending dose (SAD, 0.05-4.0 mg), multiple ascending dose (MAD, 0.5-3.0 mg), dose titration, and food effect components.Results: HE009 exhibited dose-proportional exposure, with Tmaxof 4-6 h and t1/2 of 16-24 h, supporting once-daily dosing. Steady-state was achieved by day 7 with minimal accumulation (1.7-2.0 fold). A clear concentration-effect relationship was observed, with maximum lymphocyte count reductions of 58% (SAD) and 70-80% (MAD). Notably, HE009 demonstrated a favorable cardiac safety profile, with transient, asymptomatic bradycardia mitigated by dose titration. No events related to hypertension were observed during the study period.Conclusion: These findings suggest HE009 offers potential advantages in efficacy, safety, and dosing flexibility compared to existing S1P receptor modulators for treating autoimmune disorders like systemic lupus erythematosus.Trial registration: The trial was registered on the Chinese Clinical Trial Registry, (Identifier No. ChiCTR2200066345), Registered December 1, 2022.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-15"},"PeriodicalIF":4.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231917","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

Clinical advances in investigational epilepsy treatments. 实验性癫痫治疗的临床进展。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-14 DOI: 10.1080/13543784.2025.2574992

Slobodan M Janković

{"title":"Clinical advances in investigational epilepsy treatments.","authors":"Slobodan M Janković","doi":"10.1080/13543784.2025.2574992","DOIUrl":"10.1080/13543784.2025.2574992","url":null,"abstract":"Introduction: Although innovative ways of treating epilepsy that is resistant to standard therapy are actively being researched, not many have demonstrated sufficient efficacy and safety in clinical research to obtain marketing authorization.Areas covered: The article aims to provide a concise overview of the most important investigational treatments for epilepsy that have achieved breakthroughs in clinical studies in terms of efficacy and safety. Relevant studies published between 2020 and 2025 were searched for in PubMed and Google Scholar databases, without language restrictions.Expert opinion: Although the first clinical breakthroughs have been achieved in the causal therapy of epilepsy using cell therapy and antisense oligonucleotides, larger clinical and observational studies are needed after the wider application of these therapeutic methods to evaluate their true place in epilepsy therapy. Symptomatic antiseizure medication has achieved significantly greater success in clinical practice by acting through several different mechanisms, and in the future, the reduction of the number of patients who will not respond favorably to any form of antiseizure medication could be expected.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-7"},"PeriodicalIF":4.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279414","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

An update on novel investigational agents for the treatment of primary biliary cholangitis. 治疗原发性胆管炎的新型研究药物的最新进展。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-12 DOI: 10.1080/13543784.2025.2573638

Annarosa Floreani, Daniela Gabbia, Sara De Martin

{"title":"An update on novel investigational agents for the treatment of primary biliary cholangitis.","authors":"Annarosa Floreani, Daniela Gabbia, Sara De Martin","doi":"10.1080/13543784.2025.2573638","DOIUrl":"https://doi.org/10.1080/13543784.2025.2573638","url":null,"abstract":"Introduction: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct destruction that can lead to liver cirrhosis and liver failure. While ursodeoxycholic acid (UDCA) remains the first-line treatment, up to 40% of patients show an inadequate response. In such cases, second-line therapies are explored. Obeticholic acid (OCA), a farnesoid X receptor agonist, was initially approved but recently lost its marketing authorization in the EU due to an unfavorable risk-benefit balance. Fibrates, particularly bezafibrate and fenofibrate, have shown promising results in improving biochemical markers and reducing pruritus, although they remain off-label.Areas covered: We here focus on new FDA- and EMA-approved therapies, including the PPAR agonists elafibranor and seladelpar, which demonstrate improved biochemical response and, in the case of seladelpar, a significant reduction in pruritus. Additional investigational agents include NOX inhibitors such as setanaxib, IBAT inhibitors like linerixibat and odevixibat, and golexanolone, targeting fatigue through modulation of GABAergic neurotransmission.Expert opinion: Despite advances, challenges remain in treatment personalization, access to new drugs, and identification of robust endpoints beyond ALP normalization, including quality of life improvements. Future directions emphasize a personalized approach, long-term outcome studies, and broader access to effective therapies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279372","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

Emerging ANGPTL3-directed therapies for hyperlipidemia: insights from two recent phase II trials. 新兴的angptl3导向的高脂血症治疗：来自最近两项II期试验的见解

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-07 DOI: 10.1080/13543784.2025.2571213

Amanda J Hooper, Thusyanthy Parameswaran, John R Burnett

引用次数: 0

Development of investigational radiotherapeutics for the diagnosis and treatment of glioma. 胶质瘤诊断和治疗的实验性放射疗法的发展。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-10-06 DOI: 10.1080/13543784.2025.2564966

Yuhao Shi, Sravya Koduri, Jonathan T Yang, Brandon S Imber

{"title":"Development of investigational radiotherapeutics for the diagnosis and treatment of glioma.","authors":"Yuhao Shi, Sravya Koduri, Jonathan T Yang, Brandon S Imber","doi":"10.1080/13543784.2025.2564966","DOIUrl":"10.1080/13543784.2025.2564966","url":null,"abstract":"Introduction: Gliomas are tumors that arise from glial cells in the central nervous system. Radiation provides local control for low-grade gliomas and improves survival for patients with high-grade gliomas; however, recurrence is common and treatment can be associated with long-term toxicities. Several strategies are under development to improve the anti-tumor efficacy of radiation and limit possible side effects. Novel molecular imaging agents can help diagnose new gliomas, delineate tumors for more accurate radiation planning, and differentiate tumor recurrence from treatment response changes on imaging. Radiotherapeutics provide an alternative method of delivering targeted radiation to tumors by leveraging molecular targets. New generation of radiosensitizers that target DNA damage response and cell cycle pathways aim to enhance radiation-induced cytotoxicity.Areas covered: This review summarizes emerging molecular imaging agents, radiotherapeutics, and radiosensitizers in glioma with a focus on agents currently in the early phase of clinical trials.Expert opinion: The development of new diagnostic and therapeutic agents has the potential of improving outcomes for glioma patients. As new agents are tested in clinical trials, it will be critical to consider questions regarding standardization of methodology in use/interpretation of molecular imaging techniques, appropriate dosimetry of radiotherapeutics, and cumulative toxicities with radiosensitizers.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-10"},"PeriodicalIF":4.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112370","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

Nonamyloid-beta active immunization for the treatment of Alzheimer's disease. 非淀粉样蛋白- β主动免疫治疗阿尔茨海默病。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-09-01 Epub Date: 2025-09-07 DOI: 10.1080/13543784.2025.2551352

Olivia Triplett, Nicole Varda, Boris Decourt, Marwan N Sabbagh

{"title":"Nonamyloid-beta active immunization for the treatment of Alzheimer's disease.","authors":"Olivia Triplett, Nicole Varda, Boris Decourt, Marwan N Sabbagh","doi":"10.1080/13543784.2025.2551352","DOIUrl":"10.1080/13543784.2025.2551352","url":null,"abstract":"Introduction: Alzheimer's disease (AD) is characterized by the formation of senile plaques composed of amyloid-beta (Aβ) peptides and the intraneuronal accumulation of neurofibrillary tangles composed of abnormal, hyperphosphorylated tau proteins. These act in concert to drive cognitive decline, but it is widely held that tau spread correlates better with cognitive decline than does amyloid burden. Control of AD neuropathologies with active immunizations is studied as a potential therapeutic avenue because it could build innate immunity. Although most active immunization studies have focused on Aβ targets, tau and other targets continue to be explored.Areas covered: This study aimed to identify and describe non-Aβ active immunization trials for AD treatment. A narrative review was conducted to analyze the current status of non-Aβ active immunization for AD using PubMed as the research database.Expert opinion: The potential of active immunization beyond Aβ was explored as a therapeutic strategy for AD with a focus that targets tau and provides insights into its effectiveness, associated challenges, and limitations. Results from preclinical and clinical studies were examined, highlighting the progress and the hurdles that exist. Active immunization against non-Aβ targets, such as tau, for the treatment of AD remains a promising and expanding field.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"685-693"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948479","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