Expert opinion on investigational drugs最新文献_第2页

Preclinical development of siRNA conjugates to target tumor antigens. 靶向肿瘤抗原的siRNA偶联物的临床前开发。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-24 DOI: 10.1080/13543784.2025.2511181

Takanori Kubo, Toshio Seyama

引用次数: 0

Polyvalent immunoglobulin therapy: preclinical evidence and potential for treating chemotherapy-induced peripheral neuropathy. 多价免疫球蛋白治疗：临床前证据和治疗化疗引起的周围神经病变的潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1080/13543784.2025.2522075

William Moret, Aurore Danigo, Simon Frachet, Franck Sturtz, Sylvie Bourthoumieu, Laurent Magy, Claire Demiot, Amandine Rovini

{"title":"Polyvalent immunoglobulin therapy: preclinical evidence and potential for treating chemotherapy-induced peripheral neuropathy.","authors":"William Moret, Aurore Danigo, Simon Frachet, Franck Sturtz, Sylvie Bourthoumieu, Laurent Magy, Claire Demiot, Amandine Rovini","doi":"10.1080/13543784.2025.2522075","DOIUrl":"10.1080/13543784.2025.2522075","url":null,"abstract":"Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and often debilitating complication of cancer treatment, affecting over 68% of treated patients. This condition is characterized by sensory deficits, neuropathic pain, and reduced quality of life. While polyvalent human immunoglobulins (IVIg) are established treatments for various immune-mediated neurological disorders, including certain inflammatory and autoimmune peripheral neuropathies, their role in CIPN remains unexplored in clinical settings.Areas covered: This review examines the neuroprotective properties of IVIg, focusing on approved indications, and explores recent preclinical evidence on the role of neuroinflammation in CIPN pathophysiology. We propose that IVIg could, based on preclinical findings, offer therapeutic benefits in managing CIPN without interfering with cancer treatments, provided that future clinical validation supports its efficacy and safety.Expert opinion: Although there is currently no clinical experience with IVIg in CIPN patients, preclinical data suggest promising therapeutic prospects. Future research is essential to elucidate CIPN mechanisms further and to determine how IVIg might contribute as a novel therapeutic strategy, ultimately improving the quality of life for cancer patients.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"507-518"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505307","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

Prospects for multi-focal motor neuropathy treatment by complement inhibition. 补体抑制治疗多灶性运动神经病的前景。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-30 DOI: 10.1080/13543784.2025.2511177

Hans Katzberg, Carlos Alberto Soto Rincón

引用次数: 0

Clinical progress of B7-H3 targeted antibody drug conjugate ifinatamab deruxtecan for small-cell lung cancer. B7-H3靶向抗体药物偶联物德鲁德替康治疗小细胞肺癌的临床进展

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 10.1080/13543784.2025.2512566

Mylène Wespiser, Romane Gille, Maurice Pérol

{"title":"Clinical progress of B7-H3 targeted antibody drug conjugate ifinatamab deruxtecan for small-cell lung cancer.","authors":"Mylène Wespiser, Romane Gille, Maurice Pérol","doi":"10.1080/13543784.2025.2512566","DOIUrl":"10.1080/13543784.2025.2512566","url":null,"abstract":"Introduction: Small cell lung cancer is an aggressive malignancy with limited treatment options and poor prognosis, particularly at extensive stage. While first-line platinum-etoposide chemotherapy combined with anti-PD-L1 therapy improves survival, most patients relapse, highlighting the need for novel therapies.Areas covered: B7-Homolog3 (B7-H3), an immune checkpoint molecule overexpressed in SCLC, has emerged as a promising therapeutic target. Ifinatamab deruxtecan (I-DXd) is an antibody-drug conjugate targeting B7-H3, delivering a topoisomerase I inhibitor. Early clinical trials (IDeate-PanTumor01 and IDeate-Lung01) have demonstrated encouraging results in pretreated ES-SCLC. In the 12 mg/kg cohort of IDeate-Lung01, I-DXd achieved an objective response rate of 54.8%, median progression-free survival of 5.5 months, and median overall survival of 11.8 months. Notably, it showed intracranial activity with a central nervous system-confirmed response rate of 37.8%.Expert opinion: I-DXd is currently being evaluated in the phase III IDeate-Lung02 trial. Its promising efficacy, manageable safety profile, and potential in combination strategies position it as a key candidate for future SCLC treatment.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"463-471"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150001","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

A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults. 一项随机、双盲、单剂量、平行组、两组研究，评估候选生物类似药AVT03 （60 mg/mL）在健康成年男性中的药代动力学相似性、药效学、安全性、耐受性和免疫原性。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1080/13543784.2025.2505466

Anel Pretorius, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Ruth Ruffieux, Abid Sattar, Steffen Leutz, Fausto Berti

{"title":"A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults.","authors":"Anel Pretorius, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Ruth Ruffieux, Abid Sattar, Steffen Leutz, Fausto Berti","doi":"10.1080/13543784.2025.2505466","DOIUrl":"10.1080/13543784.2025.2505466","url":null,"abstract":"Background: This study compared pharmacokinetic (PK) similarity, pharmacodynamic, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Prolia).Methods: Healthy male participants (N = 209) were randomized 1:1 to receive one 60 mg dose of either AVT03 or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters (Cmax and AUC0-inf for EMA; Cmax and AUC0-t for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC0-24, Tmax, Kel, t1/2, Vz/F, and CL/F. The serum biomarker of bone resorption, CTX-1 was evaluated to compare pharmacodynamic (PD) profiles. Safety and immunogenicity were also assessed.Results: The 90% CI for the ratio of geometric means for primary PK parameters was contained between the pre-specified margins of 80.00% and 125.00% (Cmax [102.23, 113.64]; AUC0-inf [107.17, 118.87]; AUC0-t [107.72, 120.42]), supporting demonstration of PK similarity between AVT03 and RP. Secondary PK parameters supported the analysis. PD, safety and immunogenicity profiles were comparable between the two arms.Conclusion: Results supported a demonstration of PK similarity between AVT03 and RP denosumab. Comparable PD, safety and immunogenicity profiles were also shown.Clinical trial registration: The clinical trial is registered at https://www.clinicaltrials.gov under identifier NCT05126784.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"527-537"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975096","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 development of tri-specific antibodies for immune-oncology. 免疫肿瘤学三特异性抗体的临床发展。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-25 DOI: 10.1080/13543784.2025.2511180

Zhipeng Cao, Laura D Osellame, Laura Allan, Andrew M Scott

引用次数: 0

Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD. HY-072808软膏（一种新型PDE4抑制剂）在轻中度AD青少年和成人患者中的安全性、药代动力学和疗效

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-27 DOI: 10.1080/13543784.2025.2510671

Feng Yao, Mingchao He, Jing Wang, Yao Li, Qian Zhang, Jingjing Yang, Jingying Wu, Qin Zhang, Renpeng Zhou, Meiling Zhang, Linying Meng, Liming Wu, Zhaoxing Chu, Wei Hu

{"title":"Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD.","authors":"Feng Yao, Mingchao He, Jing Wang, Yao Li, Qian Zhang, Jingjing Yang, Jingying Wu, Qin Zhang, Renpeng Zhou, Meiling Zhang, Linying Meng, Liming Wu, Zhaoxing Chu, Wei Hu","doi":"10.1080/13543784.2025.2510671","DOIUrl":"10.1080/13543784.2025.2510671","url":null,"abstract":"Background: HY-072808 is a new PDE4 inhibitor with potential anti- atopic dermatitis (AD) effects. This study aimed to investigate its safety and pharmacokinetics in healthy individuals, and subsequently, its safety, pharmacokinetics, and efficacy in patients with mild-to-moderate AD.Methods: We conducted double-blind, placebo-controlled, single and multiple ascending dose phase I clinical trials to assess the safety and pharmacokinetics of HY-072808 ointment in healthy subjects, followed by an open-label trial to evaluate its safety, pharmacokinetics, and efficacy in adolescent and adult patients with mild-to-moderate AD. The trials included 73 healthy subjects and 20 patients with AD.Results: We found that HY-072808 had a favorable safety profile, with mild and manageable adverse events reported in both healthy subjects and AD patients. The pharmacokinetic analysis revealed that systemic exposure to HY-072808 remained minimal, with drug concentrations staying in the nanogram range. Furthermore, significant improvements in eczema severity, pruritus, and quality of life were observed in patients with mild-to-moderate AD, with 57.9% of patients achieving a ≥ 75% reduction in the EASI score.Conclusion: These results indicate the potential of HY-072808 as an effective and well-tolerated treatment for mild-to-moderate AD, suggesting further clinical development for use in both adolescent and adult patients.Trial registration: Chinese Clinical Trial Registry (No. ChiCTR2400087123).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"435-447"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136189","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

Role of ROCK2 inhibitors in the treatment of chronic graft-versus-host disease. ROCK2抑制剂在慢性移植物抗宿主病治疗中的作用

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-25 DOI: 10.1080/13543784.2025.2510667

Dat Ngo, Jose Tinajero, Salman Otoukesh, Karamjeet Sandhu, Haris Ali, Shukaib Arslan, Badri Modi, Idoroenyi Amanam, Ryotaro Nakamura, Amandeep Salhotra

{"title":"Role of ROCK2 inhibitors in the treatment of chronic graft-versus-host disease.","authors":"Dat Ngo, Jose Tinajero, Salman Otoukesh, Karamjeet Sandhu, Haris Ali, Shukaib Arslan, Badri Modi, Idoroenyi Amanam, Ryotaro Nakamura, Amandeep Salhotra","doi":"10.1080/13543784.2025.2510667","DOIUrl":"10.1080/13543784.2025.2510667","url":null,"abstract":"Introduction: Chronic graft-versus-host disease (cGVHD) is the most common cause of late non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Rho-associated coiled-coiled kinases (ROCK) inhibitors have been shown to balance the pro-inflammatory and regulatory T-cell subsets in addition to reducing fibrosis in cGVHD, resulting in the development of multiple ROCK2 inhibitors including belumosudil.Areas covered: We describe the pathophysiology of cGVHD and the role of ROCK2 in cGVHD. This includes a review of the current and ongoing clinical data with belumosudil, and an overview of current ROCK2 inhibitors in development for cGVHD, including rovadicitinib, zelasudil, and GV-101.Expert opinion: Many of the recent novel agents with unique mechanisms such as ROCK2 inhibitors (i.e. belumosudil) provide high response rates but rarely yield complete responses in cGVHD. The future of management of cGVHD will rely on investigating combination therapy upfront that may achieve deeper complete responses, developing newer preventative therapies, and advancements in biomarker detection/risk stratification for cGVHD.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"391-400"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127065","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

A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development. 血管内皮生长因子基因治疗冠状动脉疾病和难治性心绞痛：临床进展评估

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-27 DOI: 10.1080/13543784.2025.2510666

Raviteja R Guddeti, Alan Wong, Steven Rudick, Geoffrey Answini, Eric Duckers, Howard C Dittrich, Timothy D Henry

{"title":"A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development.","authors":"Raviteja R Guddeti, Alan Wong, Steven Rudick, Geoffrey Answini, Eric Duckers, Howard C Dittrich, Timothy D Henry","doi":"10.1080/13543784.2025.2510666","DOIUrl":"10.1080/13543784.2025.2510666","url":null,"abstract":"Introduction: Vascular endothelial growth factor (VEGF) gene therapy is a novel treatment strategy for refractory angina (RA) that works by promoting myocardial neoangiogenesis and collateral circulation formation. XC001 (encoberminogene rezmadenovec) is a novel, replication-deficient, non-integrating recombinant adenovirus vector formally referred to as AdVEGF-All6A+ engineered to produce three isoforms of VEGF A (121, 165, and 189) that are proven to induce neoangiogenesis and constructed specifically to increase the expression of VEGF 189 and 165 to improve safety because of its heparan sulfate binding domain.Areas covered: We review the clinical development of XC001 and results of the EXACT (Epicardial delivery of encoberminogene rezmadenovec [XC001] gene therapy for refractory Angina Coronary Treatment) phase 1 and phase 2 trials.Expert opinion: In initial trials, intramyocardial XC001 has been shown to be safe with signals for efficacy in decreasing myocardial perfusion defects, improving exercise duration, and anginal complaints in patients with RA. A Phase 2 trial using a novel percutaneous delivery catheter for endomyocardial delivery of XC001 is currently underway and has potential benefits in multiple other conditions, including as an adjunct therapy in patients undergoing CABG treatment at risk for incomplete revascularization, patients with coronary microvascular dysfunction, and others with peripheral arterial disease.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"363-370"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150000","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

A randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men. BI 764198（一种瞬时受体电位通道6 （TRPC6）抑制剂）在日本健康男性中的安全性、耐受性和药代动力学的随机I期研究

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-03 DOI: 10.1080/13543784.2025.2510664

Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou

{"title":"A randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men.","authors":"Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou","doi":"10.1080/13543784.2025.2510664","DOIUrl":"10.1080/13543784.2025.2510664","url":null,"abstract":"Background: BI 764198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis.Research design and methods: Phase I study in 44 Japanese male volunteers. Single dose part: BI 764198 20 mg (n = 6) vs. placebo (n = 2); multiple dose part: BI 764198 40, 80, or 160 mg (n = 9 each) or placebo (n = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic.Results: DRAEs were reported in 20.5% (9/44) of participants (total BI 764198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764198 80 mg 11.1% [1/9]; BI 764198 160 mg 33.3% [3/9]). BI 764198 exposure increased near dose proportionally to 80 mg and was slightly higher than anticipated with 160 mg. Pharmacokinetics were similar in Asians and non-Asians after accounting for body weight. Limitations include small sample size per dose and short trial duration.Conclusions: BI 764198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers.Clinical trial registration: This study was registered on Clinical Trials.gov, identifier NCT04665700.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"425-433"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119270","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