Expert opinion on investigational drugs最新文献

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Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as a mechanistically informed therapeutic treatment for mania, mixed features and cognitive deficits in bipolar disorder? 以乙酰胆碱和毒蕈碱受体为靶点治疗双相情感障碍:xanomeline-trospium chloride和其他实验性毒蕈碱受体激动剂是否有望作为治疗躁狂症、混合特征和双相情感障碍认知缺陷的一种机制信息疗法?
IF 4.9 2区 医学
Expert opinion on investigational drugs Pub Date : 2025-06-18 DOI: 10.1080/13543784.2025.2522885
Roger S McIntyre
{"title":"Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as a mechanistically informed therapeutic treatment for mania, mixed features and cognitive deficits in bipolar disorder?","authors":"Roger S McIntyre","doi":"10.1080/13543784.2025.2522885","DOIUrl":"https://doi.org/10.1080/13543784.2025.2522885","url":null,"abstract":"<p><strong>Introduction: </strong>Xanomeline-trospium chloride (Cobenfy, KarXT) received FDA approval on 26 September 2024, for the treatment of adults with schizophrenia. Xanomeline-trospium chloride is the first muscarinic M1, M4 acetylcholine receptor partial agonist approved to treat schizophrenia. Preliminary evidence indicates that xanomeline-trospium chloride improves measures of cognition in Alzheimer's disease and schizophrenia.</p><p><strong>Areas covered: </strong>Acetylcholine's physiology and evidence implicating disturbance in acetylcholine and its canonical receptors in mania and cognitive impairment in bipolar disorder are synthesized. Extant efficacy, safety and tolerability data for xanomeline-trospium chloride in adults with schizophrenia are reviewed. Xanomeline-trospium chloride's clinical and pharmacological profile provides rationale for investigating its efficacy, safety and tolerability in the treatment of manic episodes and cognitive impairment associated with bipolar disorder.</p><p><strong>Expert opinion: </strong>Xanomeline-trospium chloride is a mechanistically novel treatment for schizophrenia targeting cholinergic receptors as opposed to dopamine receptors and may have transdiagnostic efficacy in mania and/or cognitive impairment in bipolar disorder. Xanomeline-trospium chloride is safe and generally well tolerated and does not appear to have depressogenic effects and/or increased suicidality in adults with schizophrenia. Whether other investigational muscarinic agonists (e.g. positive allosteric modulator [PAM] of M4) are potentially efficacious in mania and cognitive impairment in bipolar disorder is a future research avenue.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324916","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 of current AXL-targeting therapies in early phase cancer trials. 当前axl靶向治疗在早期癌症试验中的前景。
IF 4.9 2区 医学
Expert opinion on investigational drugs Pub Date : 2025-05-31 DOI: 10.1080/13543784.2025.2511178
Juhye Yim, Chloe Hope, Justus M Huelse, Douglas K Graham
{"title":"Prospects of current AXL-targeting therapies in early phase cancer trials.","authors":"Juhye Yim, Chloe Hope, Justus M Huelse, Douglas K Graham","doi":"10.1080/13543784.2025.2511178","DOIUrl":"10.1080/13543784.2025.2511178","url":null,"abstract":"<p><strong>Introduction: </strong>AXL, a member of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases, controls pro-tumorigenic signaling cascades and cancer-immunological functions, and promotes drug resistance. Due to AXL's multifaceted role and therapeutic activity in preclinical studies, a variety of AXL inhibitors are being developed and tested in clinical trials for cancer treatment. Some clinical studies are showing promising results for AXL inhibitors as monotherapy and in combination with standard of care therapeutics. Currently, no selective AXL-targeting therapy has reached FDA-approval, but several compounds have entered phase II and III studies.</p><p><strong>Area covered: </strong>We elaborate on the role of AXL in cancer progression and suppressing anti-cancer immunity at both the molecular level and immune cell interaction level. Additionally, we review pre-clinical and clinical data of AXL-targeting agents.</p><p><strong>Expert opinion: </strong>Preclinical and several early clinical trials demonstrated the safety of AXL-targeting monotherapies with some evidence of efficacy. Additionally, multiple novel combination regimens including AXL-targeting agents to overcome resistance mechanisms are being actively examined with some promising results. However, patient selection and companion biomarkers may be critical for the success of AXL-targeting therapies.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-33"},"PeriodicalIF":4.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141807","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 : 2025-05-30 DOI: 10.1080/13543784.2025.2511177
Hans Katzberg, Carlos Alberto Soto Rincón
{"title":"Prospects for multi-focal motor neuropathy treatment by complement inhibition.","authors":"Hans Katzberg, Carlos Alberto Soto Rincón","doi":"10.1080/13543784.2025.2511177","DOIUrl":"10.1080/13543784.2025.2511177","url":null,"abstract":"","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-5"},"PeriodicalIF":4.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132279","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 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 : 2025-05-29 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":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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%.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-9"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","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
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 : 2025-05-24 DOI: 10.1080/13543784.2025.2511181
Takanori Kubo, Toshio Seyama
{"title":"Preclinical development of siRNA conjugates to target tumor antigens.","authors":"Takanori Kubo, Toshio Seyama","doi":"10.1080/13543784.2025.2511181","DOIUrl":"10.1080/13543784.2025.2511181","url":null,"abstract":"","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-4"},"PeriodicalIF":4.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127064","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, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 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 (70 mg/mL)在健康成年男性中的药代动力学相似性、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 : 2025-05-16 DOI: 10.1080/13543784.2025.2505469
Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti
{"title":"A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults.","authors":"Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti","doi":"10.1080/13543784.2025.2505469","DOIUrl":"10.1080/13543784.2025.2505469","url":null,"abstract":"<p><strong>Background: </strong>This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva).</p><p><strong>Methods: </strong>Healthy male participants (<i>N</i> = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of AVT03, or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters C<sub>max</sub> and AUC<sub>0-t</sub> were within 80.00% and 125.00%. Additional PK parameters included AUC<sub>0-inf</sub>, t<sub>max</sub>, K<sub>el</sub>, t<sub>1/2</sub>, V<sub>z</sub>/F, and CL/F. Safety and immunogenicity were also assessed.</p><p><strong>Results: </strong>The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C<sub>max</sub> [98.26, 110.00]; AUC<sub>0-t</sub> [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms.</p><p><strong>Conclusion: </strong>Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP.</p><p><strong>Clinical trial registration: </strong>The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-8"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992716","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 : 2025-05-16 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":"<p><strong>Background: </strong>This study compared pharmacokinetic (PK) similarity, pharmacodynamic, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Prolia).</p><p><strong>Methods: </strong>Healthy male participants (<i>N</i> = 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 (C<sub>max</sub> and AUC<sub>0-inf</sub> for EMA; C<sub>max</sub> and AUC<sub>0-t</sub> for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC<sub>0-24</sub>, T<sub>max</sub>, K<sub>el</sub>, t<sub>1/2</sub>, V<sub>z</sub>/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.</p><p><strong>Results: </strong>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% (C<sub>max</sub> [102.23, 113.64]; AUC<sub>0-inf</sub> [107.17, 118.87]; AUC<sub>0-t</sub> [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.</p><p><strong>Conclusion: </strong>Results supported a demonstration of PK similarity between AVT03 and RP denosumab. Comparable PD, safety and immunogenicity profiles were also shown.</p><p><strong>Clinical trial registration: </strong>The clinical trial is registered at https://www.clinicaltrials.gov under identifier NCT05126784.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-11"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","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
{"title":"Clinical development of tri-specific antibodies for immune-oncology.","authors":"Zhipeng Cao, Laura D Osellame, Laura Allan, Andrew M Scott","doi":"10.1080/13543784.2025.2511180","DOIUrl":"10.1080/13543784.2025.2511180","url":null,"abstract":"","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"359-362"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132352","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, 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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (No. ChiCTR2400087123).</p>","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":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","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
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