Expert opinion on investigational drugs最新文献_第8页

Mass balance and absolute bioavailability of avenciguat (¹⁴C) after intravenous or oral administration in healthy male participants. 健康男性受试者静脉或口服给药后avenciguat （14C）的质量平衡和绝对生物利用度

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-13 DOI: 10.1080/13543784.2025.2612329

David Joseph, Diane Wong, Pallabi Mitra, Adam M Auclair, Taylor Wolfgang, Eric Gao, Lena Herich, Renger Tiessen

{"title":"Mass balance and absolute bioavailability of avenciguat (14C) after intravenous or oral administration in healthy male participants.","authors":"David Joseph, Diane Wong, Pallabi Mitra, Adam M Auclair, Taylor Wolfgang, Eric Gao, Lena Herich, Renger Tiessen","doi":"10.1080/13543784.2025.2612329","DOIUrl":"10.1080/13543784.2025.2612329","url":null,"abstract":"Background: Avenciguat, a potent nitric oxide-independent activator of soluble guanylyl cyclase, is being evaluated in chronic kidney disease and systemic sclerosis. We assessed avenciguat absolute bioavailability and mass balance.Research design and methods: Open-label Phase 1 trial in healthy men. Doses: Part A, 3 mg [14C]-avenciguat single dose (oral solution); Part B, 3 mg unlabeled avenciguat (tablet) then 30 µg [14C]-avenciguat (intravenous). Primary endpoints: Part A, mass balance and recovery of [14C] radioactivity in excreta; Part B, absolute bioavailability. Safety and pharmacokinetics were evaluated.Results: In Part A (N = 6), geometric mean recovery of [14C] radioactivity was 90.0% (range 80.6-96.0%). Elimination was mainly via feces (geometric mean 85.3%; range 76.5-91.3%); urine (4.66%; range 4.10-5.31%). In Part B (N = 6), the absolute bioavailability of avenciguat was 83.0%. In pooled plasma, the predominant drug-related component was avenciguat (mean 86.8%); the acyl glucuronide metabolite represented 5.2% of radioactivity. Drug-related adverse events (AEs) occurred in 33.3% (4/12) of participants, mostly mild, with one moderate presyncope event. No AEs leading to discontinuation were reported.Conclusions: Avenciguat was generally well tolerated and was primarily excreted unchanged in feces and minimally excreted in urine. After oral administration, avenciguat has high oral bioavailability.Clinical trial registration: ClinicalTrials.gov (NCT05515328).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"75-84"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899775","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

Experimental p38 MAPK inhibitors for the treatment of urological cancers: observations from early clinical trials. 实验性p38 mapk抑制剂治疗泌尿系统癌症：来自早期临床试验的观察

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-12 DOI: 10.1080/13543784.2026.2629507

Charalampos Fragkoulis, Panagiotis Velissarios Stamatakos, Nikolaos Kontolatis, Konstantinos Gklinos, Georgios Papavasileiou, Athanasios Dellis

引用次数: 0

Menin inhibitors for adult acute myeloid leukemia: 2025 update. 成人急性髓性白血病的Menin抑制剂：2025年更新。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-06 DOI: 10.1080/13543784.2025.2612321

Umar Iqbal, Julia Fadul, David A Sallman, Rory M Shallis

{"title":"Menin inhibitors for adult acute myeloid leukemia: 2025 update.","authors":"Umar Iqbal, Julia Fadul, David A Sallman, Rory M Shallis","doi":"10.1080/13543784.2025.2612321","DOIUrl":"10.1080/13543784.2025.2612321","url":null,"abstract":"Introduction: Menin inhibitors are a relatively new class of drugs that reverse oncogenesis and induce leukemic cell differentiation by blocking the interaction between the MEN1 gene product (menin) and lysine (K)-methyltransferase 2 (KMT2A). This is relevant in 50-70% of acute myeloid leukemia (AML) subsets driven by overexpression of the HOXA9/MEIS1 pathway. These patients have dismal outcomes with current options, especially in the relapsed/refractory setting.Areas covered: Here, we discuss menin pathobiology, the available and emerging clinical data for menin inhibitors, clinical nuance related to their use, and the current unmet needs that may guide future endeavors for this drug class. A literature search was conducted using PubMed/MEDLINE, Embase, and Web of Science databases. The search included articles published in English up to 25 August 2025. Keywords and Medical Subject Headings (MeSH) related to 'menin inhibitors' were combined using Boolean operators (AND, OR). Additionally, abstracts from major hematology conferences were reviewed, and the clinicaltrials.gov registry was queried for active trials as well.Expert opinion: Menin inhibitor approval/use is expanding into other HOX-driven subtypes (e.g. NPM1, NUP98r), as a frontline option and in combination settings. Monitoring for differentiation syndrome, QT interval prolongation, recognizing pseudo-progression, and supportive care needs remains essential to maximize patient benefit.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"37-48"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877799","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 insights into the potential of angiotensin type II receptor agonists as therapeutics for idiopathic pulmonary fibrosis. 血管紧张素II型受体激动剂作为特发性肺纤维化治疗药物的潜在研究见解。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-14 DOI: 10.1080/13543784.2026.2616755

Olivia N Young, Robert E Widdop, Jane E Bourke

{"title":"Investigational insights into the potential of angiotensin type II receptor agonists as therapeutics for idiopathic pulmonary fibrosis.","authors":"Olivia N Young, Robert E Widdop, Jane E Bourke","doi":"10.1080/13543784.2026.2616755","DOIUrl":"10.1080/13543784.2026.2616755","url":null,"abstract":"Introduction: Current standard-of-care for idiopathic pulmonary fibrosis is limited to nintedanib and pirfenidone, which only slow the progressive loss of lung function and have significant adverse effects that are intolerable to many patients. There is therefore a significant unmet need for alternative treatments for this incurable disease.Areas covered: This review describes emerging evidence implicating dysregulation of the renin-angiotensin system in IPF pathogenesis, and both pre-clinical and recent clinical data supporting activation of the anti-fibrotic AT2R as a promising therapeutic strategy. The efficacy of AT2R agonists across pre-clinical models of both IPF and relevant lung diseases is discussed, with a particular focus on favorable findings with the AT2R agonist C21 (buloxibutid), leading to its current clinical trials for IPF.Expert opinion: Rapid translation of C21 (now named buloxibutid), the first-in-class orally available AT2R agonist, to early phase clinical trials for IPF have established its safety and disease-modifying potential. Ongoing development of novel, more highly selective AT2R agonists may deliver the same clinical benefit as C21 with reduced off-target effects. The AT2R drug class offers great promise as novel therapeutics, potentially extending beyond IPF to other inflammatory and fibrotic lung diseases.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"63-73"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959061","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

Promising investigational agents for gastro-oesophageal junction adenocarcinoma. 有前途的研究药物用于胃-食管交界处腺癌。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2025-12-25 DOI: 10.1080/13543784.2025.2607520

Antonella Cammarota, Elizabeth Smyth

引用次数: 0

Targeting inflammation in endometriosis: emerging therapeutic options. 子宫内膜异位症的靶向炎症：新兴的治疗选择。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2026-01-07 DOI: 10.1080/13543784.2025.2609734

Umberto Perrone, Fabio Barra, Marco Anatrà, Michele Paudice, Valerio Gaetano Vellone, Giuseppe Gullo, Simone Ferrero

{"title":"Targeting inflammation in endometriosis: emerging therapeutic options.","authors":"Umberto Perrone, Fabio Barra, Marco Anatrà, Michele Paudice, Valerio Gaetano Vellone, Giuseppe Gullo, Simone Ferrero","doi":"10.1080/13543784.2025.2609734","DOIUrl":"10.1080/13543784.2025.2609734","url":null,"abstract":"Introduction: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting up to 10% of reproductive-aged women. Current therapies are predominantly hormone-based and offer symptomatic relief without correcting the immune dysregulation and inflammation that drive lesion persistence, pain, and infertility.Areas covered: This review summarizes emerging strategies that directly target inflammatory pathways in endometriosis. Key mechanisms involved in lesion survival and symptom generation include cytokine signaling (TNF-α, IL-1, IL-6), oxidative stress, immune-checkpoint dysregulation, and activation of the JAK/STAT pathway. Therapeutic approaches discussed comprise biologic agents (infliximab, etanercept, adalimumab, anakinra, tocilizumab), small-molecule JAK inhibitors (tofacitinib), and antioxidant compounds such as N-acetylcysteine, resveratrol, and vitamins C and E.Expert opinion: Targeting inflammation represents a promising shift in endometriosis management, particularly for women who do not respond to hormonal therapies or aim to conceive. Preclinical studies consistently demonstrate reductions in lesion size, inflammatory cytokines, oxidative stress, and neuroangiogenic signaling. Early clinical evidence - especially for TNF-α and IL-1 blockade and for N-acetylcysteine - suggests improvements in pain and, in selected cases, reproductive outcomes. Although preliminary, these findings support the rationale for inflammation-directed therapies. Future research should prioritize randomized trials, long-term safety and fertility assessment, and biomarker-guided patient stratification to identify responders and optimize precision use of these agents.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"995-1009"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818657","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 overview of KRAS-targeting therapies for colorectal cancer in phase I and II development. 结直肠癌I期和II期kras靶向治疗综述

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2026-01-08 DOI: 10.1080/13543784.2025.2611395

Shadi Chamseddine, Asfar Azmi, Muhammad Wasif Saif

{"title":"An overview of KRAS-targeting therapies for colorectal cancer in phase I and II development.","authors":"Shadi Chamseddine, Asfar Azmi, Muhammad Wasif Saif","doi":"10.1080/13543784.2025.2611395","DOIUrl":"10.1080/13543784.2025.2611395","url":null,"abstract":"Introduction: KRAS mutations are among the most common oncogenic alterations in colorectal cancer (CRC). These mutations play a central role in tumor initiation and progression through activation of the MAPK signaling pathway. For many years, KRAS was considered an undruggable target. However, recent advances have led to the development of allele-specific inhibitors and combination strategies that directly target KRAS-driven signaling.Areas covered: This review summarizes KRAS biology and pathway signaling; the prognostic and predictive impact of KRAS variants in CRC; and the emerging therapeutic landscape focused on phase I - II assets. We cover direct KRAS inhibitors (including G12C and non-G12C programs), pan-KRAS/'RAS-ON' and SOS1/SHP2 strategies, vertical MAPK/PI3K co-inhibition, metabolic and ferroptosis approaches, and translational immuno-oncology (checkpoint blockade in MSI-H/dMMR disease, cellular therapies, and vaccines). We also outline ongoing clinical trials, resistance mechanisms, biomarker considerations (tumor sidedness, co-mutations), and practical implications for sequencing and combinations.Expert opinion: KRAS-targeted therapy in CRC is entering a clinically actionable era. Allele-specific inhibitors are likely to find their place in combinations that suppress adaptive bypass (e.g. SOS1/SHP2, MEK/ERK, EGFR) while leveraging immunotherapy or metabolic vulnerabilities. Prospective biomarker integration and resistance-informed trial designs will be decisive in translating early signals into durable patient benefit.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1011-1021"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917300","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

Placebo-controlled trial of pharmacokinetics, pharmacodynamics and tolerability of KL130008 capsule in patients with rheumatoid arthritis. 类风湿关节炎患者KL130008胶囊药代动力学、药效学和耐受性的安慰剂对照试验

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2025-12-15 DOI: 10.1080/13543784.2025.2599454

Yue Cheng, Xiaohong Zhu, Zhihui Liu, Ying Wang, Yuchun Men, Huifang Wang, Miao He, Man Chen, Shuangqing Du, Bingjie Wu, Yezhe Cheng, Xiaoping Jin, Junyou Ge, Hui Lin, Ping Feng

{"title":"Placebo-controlled trial of pharmacokinetics, pharmacodynamics and tolerability of KL130008 capsule in patients with rheumatoid arthritis.","authors":"Yue Cheng, Xiaohong Zhu, Zhihui Liu, Ying Wang, Yuchun Men, Huifang Wang, Miao He, Man Chen, Shuangqing Du, Bingjie Wu, Yezhe Cheng, Xiaoping Jin, Junyou Ge, Hui Lin, Ping Feng","doi":"10.1080/13543784.2025.2599454","DOIUrl":"10.1080/13543784.2025.2599454","url":null,"abstract":"Background: KL130008, a novel selective JAK1/JAK2 inhibitor demonstrated acceptable safety and tolerability in Phase I studies involving healthy volunteers. This proof-of-concept trial aimed to characterize the pharmacokinetic/pharmacodynamics relationship and preliminary efficacy of KL130008 in rheumatoid arthritis (RA) patients.Research design and methods: In this randomized, double-blind, single-center trial involving 30 RA patients, 24 received oral KL130008 and 6 received placebo. Pharmacokinetics and pharmacodynamics were evaluated based on drug concentrations and on inhibition of phospho-signal transducer and activator of transcription-3 (pSTAT3). Safety and efficacy outcomes were assessed.Results: Pharmacokinetics were linear over the dose from 1-4 mg; the drug showed the half-life of 14.34-18.14 h and accumulation factor of 1.27-1.76. The drug inhibited pSTAT3 with a dose-dependent trend, achieving maximal inhibition of 37.61% (1 mg), 61.28% (2 mg), and 71.87% (4 mg). The American College of Rheumatology 20 responses (≥20% improvement from baseline) were 25.0-37.5% across the dose range of 1-4 mg after two weeks of multiple dosing, higher than 16.7% for placebo. Treatment-emergent adverse events, all mild, occurred in two-thirds of patients receiving KL130008.Conclusion: In RA patients, oral KL130008 shows linear pharmacokinetics, pSTAT3 inhibition, and promising safety. Efficacy are exploratory given the small sample size.Trial registration: Registered in the Chinese Clinical Trial Register (ChiCTR2000029360).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1023-1032"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654150","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

Advancements of investigational agents for renal cell carcinoma: what clinical progress have we seen in the last 5 years? 肾细胞癌研究药物的进展：在过去的5年中我们看到了哪些临床进展？

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2025-12-27 DOI: 10.1080/13543784.2025.2606118

Linda Danielli, Matteo Rosellini, Elisa Tassinari, Andrea Marchetti, Veronica Mollica, Matteo Santoni, Francesco Massari

{"title":"Advancements of investigational agents for renal cell carcinoma: what clinical progress have we seen in the last 5 years?","authors":"Linda Danielli, Matteo Rosellini, Elisa Tassinari, Andrea Marchetti, Veronica Mollica, Matteo Santoni, Francesco Massari","doi":"10.1080/13543784.2025.2606118","DOIUrl":"10.1080/13543784.2025.2606118","url":null,"abstract":"Introduction: RCC management has evolved toward immunotherapy-based strategies, with adjuvant anti-PD-1 therapy after nephrectomy and immune-VEGF TKI combinations in the metastatic setting now representing standards of care. Outcomes remain variable because of biological heterogeneity, treatment resistance, and the limited performance of currently available biomarkers.Areas covered: This review synthesizes contemporary standards of care together with advances in tumor biology and biomarker development, and appraises investigational modalities across immune, targeted, and cellular platforms. We analyze how standards of care and translational insights have evolved in recent years, outlining the principal directions of current and investigational treatments.Expert opinion: The field is moving toward biology-informed treatment selection. Priorities include prospective validation of biomarker strategies, standardization of assay platforms, and integration of dynamic response measures to refine treatment selection, sequencing, and combinations. Molecularly defined subsets and less common histologies warrant dedicated, adequately powered studies. With rigorous methodology and standardized testing methods, emerging approaches have the potential to translate current signals into more consistent and durable clinical benefits in RCC.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"961-977"},"PeriodicalIF":4.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780740","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

Targeting aldosterone in sleep apnea: opening a new therapeutic era. 针对醛固酮治疗睡眠呼吸暂停：开启一个新的治疗时代。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-12-01 Epub Date: 2025-12-17 DOI: 10.1080/13543784.2025.2605074

Federica Fogacci, Claudio Borghi, Arrigo F G Cicero

引用次数: 0