Expert opinion on investigational drugs最新文献_第10页

Experimental autotaxin inhibitors for the treatment of idiopathic pulmonary fibrosis. 用于治疗特发性肺纤维化的实验性自体表皮生长因子抑制剂。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 DOI: 10.1080/13543784.2024.2305126

Jacopo Simonetti, Marco Ficili, Giacomo Sgalla, Luca Richeldi

{"title":"Experimental autotaxin inhibitors for the treatment of idiopathic pulmonary fibrosis.","authors":"Jacopo Simonetti, Marco Ficili, Giacomo Sgalla, Luca Richeldi","doi":"10.1080/13543784.2024.2305126","DOIUrl":"10.1080/13543784.2024.2305126","url":null,"abstract":"Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible, and fatal lung disease with unmet medical needs. Autotaxin (ATX) is an extracellular enzyme involved in the generation of lysophosphatidic acid (LPA). Preclinical and clinical data have suggested the ATX-LPAR signaling axis plays an important role in the pathogenesis and the progression of IPF.Areas covered: The aim of this review is to provide an update on the available evidence on autotaxin inhibitors in IPF and further details on the ongoing clinical studies involving these molecules.Expert opinion: The development of autotaxin inhibitors as a potential therapy for idiopathic pulmonary fibrosis has gained attention due to evidence of their involvement in the disease. Preclinical and early-phase clinical studies have explored these inhibitors' efficacy and safety, offering a novel approach in treating this disease. Combining autotaxin inhibitors with existing anti-fibrotic agents is considered for enhanced therapeutic effects. Large phase III trials assessed Ziritaxestat but yielded disappointing results, highlighting the importance of long-term observation and clinical outcomes in clinical research. Patient stratification and personalized medicine are crucial, as pulmonary fibrosis is a heterogeneous disease. Ongoing research and collaboration are essential for this advancement.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"133-143"},"PeriodicalIF":6.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650648","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

The impact of current investigational drugs for acne on future treatment strategies. 目前正在研究的痤疮治疗药物对未来治疗策略的影响。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-02-19 DOI: 10.1080/13543784.2024.2313091

Heli A Patel, Lily Guo, Steven R Feldman

引用次数: 0

Novel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials. 治疗肾上腺功能不全的新型药物：临床前和早期临床试验结果。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-02-05 DOI: 10.1080/13543784.2024.2311207

Andrew Peel, R Louise Rushworth, David J Torpy

{"title":"Novel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials.","authors":"Andrew Peel, R Louise Rushworth, David J Torpy","doi":"10.1080/13543784.2024.2311207","DOIUrl":"10.1080/13543784.2024.2311207","url":null,"abstract":"Introduction: Adrenal insufficiency currently affects over 300/million population, with higher morbidity and mortality compared to the general population. Current glucocorticoid replacement therapy is limited by a lack of reliable biomarkers to guide dosing, inter-patient variation in metabolism and narrow therapeutic window. Increased morbidity and mortality may relate to unappreciated under- or over-exposure to glucocorticoids and impaired cortisol circadian rhythm. New agents are required to emulate physiological cortisol secretion and individualize glucocorticoid dosing.Areas covered: History of glucocorticoid therapy, current limitations, and novel chronotherapeutic glucocorticoid delivery mechanisms. Literature search incorporated searches of PubMed and Embase utilizing terms such as adrenal insufficiency, Chronocort, Plenadren, continuous subcutaneous hydrocortisone infusion (CHSI), and glucocorticoid receptor modulator.Expert opinion: Glucocorticoid chronotherapy is necessary to optimize glucocorticoid exposure and minimize complications. Current oral chronotherapeutics provide improved dosing functionality, but are modifiable only in specific increments and cannot accommodate ultradian cortisol variation. Current data show improvement in quality of life but not morbidity or mortality outcomes. CHSI has significant potential for individualized glucocorticoid dosing, but would require a suitable biomarker of glucocorticoid adequacy to be implementable. Avenues for future research include determining a glucocorticoid sufficiency biomarker, development of interstitial or systemic cortisol monitoring, or development of glucocorticoid receptor modulators.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"115-126"},"PeriodicalIF":6.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570125","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

Potential of muvalaplin as a lipoprotein(a) inhibitor. muvalaplin作为脂蛋白（a）抑制剂的潜力。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2302592

Amanda J Hooper, P Mihika S Fernando, John R Burnett

引用次数: 0

Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review. 用于治疗哮喘的研究性胸腺基质淋巴细胞生成素抑制剂：系统综述。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2305144

Paola Rogliani, Gian Marco Manzetti, Federica Roberta Bettin, Maria D'Auria, Luigino Calzetta

{"title":"Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review.","authors":"Paola Rogliani, Gian Marco Manzetti, Federica Roberta Bettin, Maria D'Auria, Luigino Calzetta","doi":"10.1080/13543784.2024.2305144","DOIUrl":"10.1080/13543784.2024.2305144","url":null,"abstract":"Introduction: Severe asthma patients often remain uncontrolled despite high-intensity therapies. Biological therapies targeting thymic stromal lymphopoietin (TSLP), a key player in asthma pathogenesis, have emerged as potential options. Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab.Areas covered: This systematic review assesses the efficacy and safety of investigational TSLP inhibitors across different stages of development for asthma treatment.Expert opinion: TSLP contributes to airway inflammation, making it a pivotal therapeutic target. Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor. Some studies include mild and moderate asthma patients, suggesting the potential for extending biological therapy to non-severe patients. This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"39-49"},"PeriodicalIF":6.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416775","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, metabolism, excretion and safety of iruplinalkib (WX-0593), a novel ALK inhibitor, in healthy subjects: a phase I human radiolabeled mass balance study. 新型 ALK 抑制剂依鲁帕替尼（WX-0593）在健康受试者中的药代动力学、代谢、排泄和安全性：I 期人体放射性标记质量平衡研究。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2305134

Yicong Bian, Sheng Ma, Qingqing Yao, Tao Hu, Mingjing Ge, Hongting Li, Shansong Zheng, Zheming Gu, Hao Feng, Zhenwen Yu, Chenrong Huang, Hua Zhang, Limei Zhao, Liyan Miao

{"title":"Pharmacokinetics, metabolism, excretion and safety of iruplinalkib (WX-0593), a novel ALK inhibitor, in healthy subjects: a phase I human radiolabeled mass balance study.","authors":"Yicong Bian, Sheng Ma, Qingqing Yao, Tao Hu, Mingjing Ge, Hongting Li, Shansong Zheng, Zheming Gu, Hao Feng, Zhenwen Yu, Chenrong Huang, Hua Zhang, Limei Zhao, Liyan Miao","doi":"10.1080/13543784.2024.2305134","DOIUrl":"10.1080/13543784.2024.2305134","url":null,"abstract":"Background: Iruplinalkib is a novel anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive crizotinib-resistant NSCLC.Research design and methods: A single oral dose of 120 mg/3.7 MBq [14C]iruplinalkib was administered to healthy subjects. Blood, urine and fecal samples were collected and analyzed for iruplinalkib and its metabolites. The safety of iruplinalkib was also assessed.Results: Iruplinalkib was absorbed quickly and eliminated slowly from plasma, with a Tmax of 1.5 h and t1/2 of 28.6 h. About 88.85% of iruplinalkib was excreted at 312 h, including 20.23% in urine and 68.63% in feces. Seventeen metabolites of iruplinalkib were identified, and M3b (demethylation), M7 (cysteine conjugation), M11 (oxidative dehydrogenation and cysteine conjugation of M3b) and M12 (oxidative dehydrogenation and cysteine conjugation) were considered the prominent metabolites in humans. Iruplinalkib-related compounds were found to be covalently bound to proteins, accounting for 7.70% in plasma and 17.96% in feces, which suggested chemically reactive metabolites were formed. There were no serious adverse events observed in the study.Conclusions: Iruplinalkib was widely metabolized and excreted mainly through feces in humans. Unchanged iruplinalkib, cysteine conjugates and covalent protein binding products were the main drug-related compounds in circulation. Iruplinalkib was well tolerated at the study dose.Trial registration: The trial is registered at ClinicalTrials.gov (Identifier: Anonymized).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"63-72"},"PeriodicalIF":6.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466336","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

Bemnifosbuvir (BEM, AT-527), a novel nucleotide analogue inhibitor of the hepatitis C virus NS5B polymerase. Bemnifosbuvir（BEM，AT-527）是一种新型的丙型肝炎病毒 NS5B 聚合酶核苷酸类似物抑制剂。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2305137

Xiao-Jian Zhou, Steven S Good, Keith Pietropaolo, Qi Huang, Adel Moussa, Janet Mj Hammond, Jean-Pierre Sommadossi

{"title":"Bemnifosbuvir (BEM, AT-527), a novel nucleotide analogue inhibitor of the hepatitis C virus NS5B polymerase.","authors":"Xiao-Jian Zhou, Steven S Good, Keith Pietropaolo, Qi Huang, Adel Moussa, Janet Mj Hammond, Jean-Pierre Sommadossi","doi":"10.1080/13543784.2024.2305137","DOIUrl":"10.1080/13543784.2024.2305137","url":null,"abstract":"Introduction: Chronic hepatitis C virus (HCV) persists as a public health concern worldwide. Consequently, optimizing HCV therapy remains an important objective. While current therapies are generally highly effective, advanced antiviral agents are needed to maximize cure rates with potentially shorter treatment durations in a broader patient population, particularly those patients with advanced diseases who remain difficult to treat.Areas covered: This review summarizes the in vitro anti-HCV activity, preclinical pharmacological properties of bemnifosbuvir (BEM, AT-527), a novel prodrug that is metabolically converted to AT-9010, the active guanosine triphosphate analogue that potently and selectively inhibits several viral RNA polymerases, including the HCV NS5B polymerase. Results from clinical proof-of-concept and phase 2 combination studies are also discussed.Expert opinion: BEM exhibits potent pan-genotype activity against HCV, and has favorable safety, and drug interaction profiles. BEM is approximately 10-fold more potent than sofosbuvir against HCV genotypes (GT) tested in vitro. When combined with a potent NS5A inhibitor, BEM is expected to be a promising once-daily oral antiviral for chronic HCV infection of all genotypes and fibrosis stages with potentially short treatment durations.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"9-17"},"PeriodicalIF":6.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541943","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

Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration. JX11502MA 在中国健康受试者中的安全性、耐受性和药代动力学：一项首次在人体中进行的单剂量给药后随机、双盲、安慰剂对照研究。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2023.2291470

Yimin Yu, Jingjing He, Zhiwei Huang, Yan Li, Ying Wu, Yifeng Shen, Yanling Zhou, Cungang Bao, Zhiping Jin, Huafang Li

{"title":"Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration.","authors":"Yimin Yu, Jingjing He, Zhiwei Huang, Yan Li, Ying Wu, Yifeng Shen, Yanling Zhou, Cungang Bao, Zhiping Jin, Huafang Li","doi":"10.1080/13543784.2023.2291470","DOIUrl":"10.1080/13543784.2023.2291470","url":null,"abstract":"Background: JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia.Methods: A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment.Results: Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median Tmax ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%).Conclusions: JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia.Trial registration: https://clinicaltrials.gov (identifier: NCT05233657).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"51-61"},"PeriodicalIF":6.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487057","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

Elinzanetant: a phase III therapy for postmenopausal patients with vasomotor symptoms. 艾林扎尼坦：绝经后血管运动症状患者的 III 期疗法。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2305122

Jenifer Sassarini, Richard A Anderson

{"title":"Elinzanetant: a phase III therapy for postmenopausal patients with vasomotor symptoms.","authors":"Jenifer Sassarini, Richard A Anderson","doi":"10.1080/13543784.2024.2305122","DOIUrl":"10.1080/13543784.2024.2305122","url":null,"abstract":"Introduction: Menopausal vasomotor symptoms (VMS) are experienced by most women and are often debilitating and can last for years. While hormone replacement therapy is effective, it carries risks that have impacted its wider use, and it can be contraindicated. There is a large unmet need for a safe, effective non-hormonal therapy.Areas covered: The importance of the neurokinin (NK) system in the hypothalamic regulation of the vasomotor center has become clear. NK antagonists, previously developed for other indications, have therefore been investigated for the treatment of VMS. Elinzanetant is a potent antagonist at both NK1 (endogenous ligand Substance P) and NK3 (neurokinin B) receptors, whereas other related drugs in development are selective NK3 antagonists. Elinzanetant has been investigated in 2 Phase II trials for menopausal VMS, demonstrating rapid onset and dose-dependant efficacy for the relief of VMS and improvement in quality of life for up to 12 weeks. Phase III trials are underway in women both with physiological menopause and after treatment for breast cancer.Expert opinion: Elinzanetant is a very promising non-hormonal approach to a highly prevalent symptom constellation, with rapid onset and high efficacy. Wider indications are being explored in current Phase III trials.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"19-26"},"PeriodicalIF":6.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466334","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

Approaches to combating methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections. 抗耐甲氧西林金黄色葡萄球菌（MRSA）生物膜感染的方法。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-01-01 Epub Date: 2024-02-12 DOI: 10.1080/13543784.2024.2305136

Katherine Y Le, Michael Otto

引用次数: 0