Expert opinion on investigational drugs最新文献_第7页

Evaluation of pharmacokinetic and pharmacodynamic similarity of an IDegAsp biosimilar versus the originator in healthy Chinese volunteers. IDegAsp生物仿制药与原药在中国健康志愿者体内的药代动力学和药效学相似性评价

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-02-11 DOI: 10.1080/13543784.2025.2463085

Hui Liu, Yang Xiong, Xinlei Chen, Hongling Yu, Li Lan, Wengang He, Wenjia Wang, Yulei Zhuang, Li Deng, Kanghua Huang, Linfeng Guo, Yerong Yu

{"title":"Evaluation of pharmacokinetic and pharmacodynamic similarity of an IDegAsp biosimilar versus the originator in healthy Chinese volunteers.","authors":"Hui Liu, Yang Xiong, Xinlei Chen, Hongling Yu, Li Lan, Wengang He, Wenjia Wang, Yulei Zhuang, Li Deng, Kanghua Huang, Linfeng Guo, Yerong Yu","doi":"10.1080/13543784.2025.2463085","DOIUrl":"10.1080/13543784.2025.2463085","url":null,"abstract":"Objectives: 22011 is an insulin degludec/insulin aspart co-formulation (IDegAsp) that shares an identical amino acid sequence with Ryzodeg, the originator IDegAsp. This study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD), and safety of 22011 with Ryzodeg.Methods: In a single-center, randomized, open-label, two-treatment, two-period, two-sequence, crossover, euglycemic clamp study, healthy Chinese adults were randomized to receive 0.5 U/kg of 22011 and Ryzodeg under fasting conditions. PK was evaluated for up to 120 h and PD (represented by glucose infusion rate [GIR]) was assessed for up to 24 h.Results: Of 46 subjects randomized, all completed both treatment periods and were included in the PK/PD and safety analysis set. Insulin exposure (AUCIDeg, 0-24 h, AUCIAsp, 0-12 h, and Cmax, IAsp) and activity (GIRmax and AUCGIR, 0-24 h) were comparable (estimates of treatment ratios 0.916 ~ 1.076 for primary PK parameters and 0.946 ~ 1.037 for primary PD parameters), with 90% confidence intervals for the ratios of least square means falling within the range of 0.80 ~ 1.25. Adverse events were similar for both products and no significant safety concerns were noted in the laboratory results, vital signs, or electrocardiogram.Conclusion: This study demonstrated the PK/PD similarity of 22011 to Ryzodeg with a comparable safety profile.Trial Registration: http://www.chinadrugtrials.org.cn/index.html with an identifier of CTR20230678, registered 15 March 2023.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"97-104"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390579","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

Are glucagon-like peptide-1 (GLP-1) receptor agonists useful in treating Parkinson's disease (PD)? Does the clinical trial with lixisenatide add anything? 胰高血糖素样肽-1（GLP-1）受体激动剂对治疗帕金森病（PD）是否有用？利血那肽的临床试验有什么新进展吗？

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1080/13543784.2025.2459409

Sheila A Doggrell

{"title":"Are glucagon-like peptide-1 (GLP-1) receptor agonists useful in treating Parkinson's disease (PD)? Does the clinical trial with lixisenatide add anything?","authors":"Sheila A Doggrell","doi":"10.1080/13543784.2025.2459409","DOIUrl":"10.1080/13543784.2025.2459409","url":null,"abstract":"Introduction: Parkinson's disease (PD) is a common neurodegenerative disease. Glucagon-like peptide-1 (GLP-1) receptor agonists decrease the incidence of developing PD and are being considered for the treatment of PD.Areas covered: A phase 2 clinical trial of lixisenatide, a GLP-1 receptor agonist, in the early stages of PD. The primary endpoint was the MDS-UPDRS part 3 motor changes in score from baseline to 12 months in the on-medication state, and this was improved by lixisenatide. Post hoc subgroup analysis suggested that this effect of lixisenatide was greater in the <60-year-olds than in the ≥60 years. None of the secondary/exploratory mostly non-motor endpoints were significantly altered by lixisenatide.Expert opinion: Although the scores between lixisenatide and placebo were statistically significantly different, the difference did not quite reach clinical significance. Lixisenatide, like exenatide, had no effect on the primary or secondary endpoints at 6 months suggesting that any benefits with GLP-1 receptor agonists in PD require long-term treatment. The apparent differences in the two age groups may be due to the bigger deterioration of motor scores in the <60-year-old group. Lixisenatide has promise but does not answer the discussion on GLP-1 receptor agonist treatment for PD.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"11-15"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046123","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

CD38 monoclonal antibody felzartamab for late antibody-mediated rejection: a phase II drug evaluation. CD38单克隆抗体felzartamab治疗晚期抗体介导的排斥反应：一项II期药物评估。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-02-13 DOI: 10.1080/13543784.2025.2463092

Katharina A Mayer, Klemens Budde, Martina Schatzl, Eva Schrezenmeier, Matthias Diebold, Bernd Jilma, Georg A Böhmig

{"title":"CD38 monoclonal antibody felzartamab for late antibody-mediated rejection: a phase II drug evaluation.","authors":"Katharina A Mayer, Klemens Budde, Martina Schatzl, Eva Schrezenmeier, Matthias Diebold, Bernd Jilma, Georg A Böhmig","doi":"10.1080/13543784.2025.2463092","DOIUrl":"10.1080/13543784.2025.2463092","url":null,"abstract":"Introduction: Felzartamab is a novel, fully human CD38 monoclonal antibody, currently in development for the treatment of antibody-mediated rejection (AMR) following kidney transplantation.Areas covered: This review focuses on current phase II trials of felzartamab in AMR and other immune-mediated kidney diseases. Specifically, it discusses the drug's mechanism of action, current phase of clinical development, potential future applications and regulatory status.Expert opinion: CD38 is an activation marker expressed on the surface of plasma cells and immune cells, including natural killer cells (NK cells) cells. In a recent phase II randomized, placebo-controlled clinical trial, felzartamab demonstrated an acceptable safety and side-effect profile in patients with AMR after kidney transplantation. Efficacy outcomes suggested potential therapeutic benefits, including significant reductions in morphologic and molecular AMR activity. Given the mixed results of previous clinical trials for AMR treatments, the novel approach of targeting both antibody-secreting plasma cells and innate effector cells such as CD38+ NK cells may offer a promising new therapeutic strategy. Felzartamab is also being investigated for the treatment of other antibody-mediated kidney diseases, such as lupus nephritis, primary membranous nephropathy and IgA nephropathy. If proven effective, it could expand the therapeutic options for kidney transplant rejection and primary kidney diseases.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-10"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381921","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 gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis. 基因表达抑制剂治疗特发性肺纤维化的研究。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-02-11 DOI: 10.1080/13543784.2025.2462592

Paolo Spagnolo, Roberto Tonelli, Marco Mura, William Reisman, Vasilina Sotiropoulou, Argyrios Tzouvelekis

{"title":"Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis.","authors":"Paolo Spagnolo, Roberto Tonelli, Marco Mura, William Reisman, Vasilina Sotiropoulou, Argyrios Tzouvelekis","doi":"10.1080/13543784.2025.2462592","DOIUrl":"10.1080/13543784.2025.2462592","url":null,"abstract":"Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown cause that occurs primarily in older adults and is associated with poor quality of life and substantial healthcare utilization. IPF has a dismal prognosis. Indeed, first-line therapy, which includes nintedanib and pirfenidone, does not stop disease progression and is often associated with tolerability issues. Therefore, there remains a high medical need for more efficacious and better tolerated treatments.Areas covered: Gene therapy is a relatively unexplored field of research in IPF that has the potential to mitigate a range of profibrotic pathways by introducing genetic material into cells. Here, we summarize and critically discuss publications that have explored the safety and efficacy of gene therapy in experimentally-induced pulmonary fibrosis in animals, as clinical studies in humans have not been published yet.Expert opinion: The application of gene therapy in pulmonary fibrosis requires further investigation to address several technical and biological hurdles, improve vectors' design, drug delivery, and target selection, mitigate off-target effects and develop markers of gene penetration into target cells. Long-term clinical data are needed to bring gene therapy in IPF one step closer to practice.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"61-80"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364193","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

Early investigational agents for the treatment of rosacea: drugs in phase I and II clinical development. 治疗酒渣鼻的早期研究药物：处于I期和II期临床开发的药物。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-02-09 DOI: 10.1080/13543784.2025.2463093

Shannon K Moran, Summer C Wong, Sarah L Taylor, Steven R Feldman

{"title":"Early investigational agents for the treatment of rosacea: drugs in phase I and II clinical development.","authors":"Shannon K Moran, Summer C Wong, Sarah L Taylor, Steven R Feldman","doi":"10.1080/13543784.2025.2463093","DOIUrl":"10.1080/13543784.2025.2463093","url":null,"abstract":"Introduction: Rosacea is a multifactorial chronic dermatologic condition with a psychosocial burden for patients. There are topical, systemic, laser, and light treatments FDA-approved, but many patients remain under- or non-responsive to those available, leaving a need for more options.Areas covered: Based on a literature search using databases, PubMed, Embase, Cochrane Library, and Clinicaltrials.gov, using keywords 'rosacea clinical trials,' we discuss treatments undergoing phase I and II clinical trials for rosacea, as well as other early clinical studies.Expert opinion: The evolving understanding of rosacea's multifaceted pathophysiology, including neurovascular dysregulation and immune responses, has led to exploration of novel treatments. Mainstays of treatment are topical and systemic antibiotics, topical vasoconstrictors, pulsed dye laser, and intense pulsed light. However, even with these treatment options, some patients remain unsatisfied with results. Addressing the underlying pathophysiology of rosacea may be more effective than a siloed approach. Therapies on the horizon, such as phosphodiesterase-4 inhibitors, biologics, topical tyrosine kinase inhibitors, neurotoxin, topical probiotics, Dermaceuticals, oral tranexamic acid, oral supplements, and neuropeptide modulators are investigated as targeted interventions. Use of lasers in synergy with topical treatments offers a multipronged personalized approach. While management remains challenging, ongoing research provides promise for additional effective and individualized treatment plans.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"27-36"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364187","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

Tumor immunology and immunotherapy for endometrial cancer. 子宫内膜癌的肿瘤免疫学和免疫治疗。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-02-11 DOI: 10.1080/13543784.2025.2463091

Kosuke Murakami, Shiki Takamura, Kazuhiro Kakimi, Noriomi Matsumura

{"title":"Tumor immunology and immunotherapy for endometrial cancer.","authors":"Kosuke Murakami, Shiki Takamura, Kazuhiro Kakimi, Noriomi Matsumura","doi":"10.1080/13543784.2025.2463091","DOIUrl":"10.1080/13543784.2025.2463091","url":null,"abstract":"Introduction: Recent clinical trials show the efficacy of immune checkpoint inhibitors (ICIs) or a combination of ICI and poly (ADP-ribose) polymerase (PARP) inhibitors for advanced or recurrent endometrial cancer. However, the basis for such treatment effects remains unclear, hindering the advancement of personalized therapy.Areas covered: This review includes a detailed interpretation of subgroup analysis data from phase III clinical trials for endometrial cancer evaluating the efficacy of chemotherapy plus ICIs (NRG-GY018, RUBY, AtTEnd, KEYNOTE-B21) or chemotherapy plus ICI with/without olaparib (DUO-E). We focused on the relationship between obesity, the effect of PARP inhibitors, and tumor immunity in endometrial cancer, searched for relevant literature published from 2000 to 2024 in PubMed, and conducted a narrative review.Expert opinion: Chemotherapy plus ICI is appropriate for dMMR. Chemotherapy plus ICI and PARP inhibitor may be appropriate for TP53abn type or serous carcinoma because PARP inhibitor enhances the efficacy of ICI by activating the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway. Obese patients may benefit more from ICIs, and this appears to cause the variation in efficacy between regions/countries. Administration for measurable disease appears important to increase the effect of ICIs. Diet and exercise may also be important factors.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"37-48"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255206","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

First-in-human study on tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of XKH001, a recombinant humanized monoclonal antibody against IL-25 in healthy Chinese volunteers. 抗IL-25重组人源化单克隆抗体XKH001在中国健康志愿者体内单次和多次递增剂量耐受性、药代动力学和药效学的首次人体研究

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2025-01-20 DOI: 10.1080/13543784.2025.2453162

Hong Zhang, Wenbo Zheng, Ran Peng, Dandan Wu, Yue Hu, Tiantian Sun, Lei Gao, Yusi Liu, Li Guo, Yanhua Ding, Li Liu

{"title":"First-in-human study on tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of XKH001, a recombinant humanized monoclonal antibody against IL-25 in healthy Chinese volunteers.","authors":"Hong Zhang, Wenbo Zheng, Ran Peng, Dandan Wu, Yue Hu, Tiantian Sun, Lei Gao, Yusi Liu, Li Guo, Yanhua Ding, Li Liu","doi":"10.1080/13543784.2025.2453162","DOIUrl":"10.1080/13543784.2025.2453162","url":null,"abstract":"Background: XKH001 is a recombinant humanized IgG1 monoclonal antibody against IL-25 for the treatment of type 2 inflammatory diseases. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of XKH001 in humans for the first time.Research design and methods: This clinical investigation adopted a randomized, double-blind, and placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) design.Results: XKH001 was well tolerated in healthy Chinese subjects. Following repeated administration, XKH001 showed a slow absorption with a median Tmax of 4-7 days and a mean half-life (t1/2) of 22-25 days. The accumulation ratio ranged from 1.34 to 1.99. The exposure was mostly dose proportional, with a mean slope of 0.85-1.06. All subjects tested negative for ADA (except three subjects tested positive). The subjects who received 600 mg XKH001 in the MAD study showed a 78.2 ng/mL decrease in the total immunoglobulin E (IgE) level 85 days after the first administration, while the subjects who received matched placebo exhibited only an 8.6 ng/mL decrease.Conclusions: XKH001 showed favorable safety and pharmacokinetics profiles and a low immunogenicity in its first-in-human study. The data support its further clinical evaluation in patients with type 2 inflammatory diseases.Trial registration: The study was registered in ClinicalTrials.gov (NCT05991661).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"81-87"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002865","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

Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial. GR1603注射在健康受试者中的耐受性、安全性和药代动力学：一项随机、双盲、安慰剂对照的单剂量递增临床试验

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-01-01 Epub Date: 2024-12-20 DOI: 10.1080/13543784.2024.2443756

Xin Huang, Xiang Hong, Shuang Yang, Ling Ye, Xiaoyan Yang, Chang Cui, Qian Wu, Wei Wang, Jie Huang, Guoping Yang

{"title":"Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial.","authors":"Xin Huang, Xiang Hong, Shuang Yang, Ling Ye, Xiaoyan Yang, Chang Cui, Qian Wu, Wei Wang, Jie Huang, Guoping Yang","doi":"10.1080/13543784.2024.2443756","DOIUrl":"10.1080/13543784.2024.2443756","url":null,"abstract":"Background: GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers.Methods: Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603. Follow-up was 12 weeks. Adverse event (AE) profiles, vital signs, and blood samples were collected for assessment of safety, PK, and expression of type I interferon inducible genes.Results: Of the 46 subjects, 44 completed treatment. In the experimental group of 34 subjects (mean age 26.6 years), 30 experienced treatment-emergent adverse events (TEAEs), with a total of 102 occurrences, resulting in an incidence rate of 88.2%. The most commonly reported drug-related AEs were upper respiratory tract infection (17.6%), all of which were ≤ grade 2. GR1603 exhibits non-linear PK in the dose range of 0.1 mg/kg to 9 mg/kg. All samples were negative for anti-drug antibodies before and after dosing. The degrees of IFN gene signature were significantly inhibited in the higher dose groups.Conclusion: The safety/tolerability, PK and exploratory metrics observed in this study support further clinical development of GR1603.Clinical trial registration: www.chictr.org.cn/searchproj.html identifier is ChiCTR2100045628.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"89-95"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834429","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

Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction. MASH的生存期：弥合肝脏和全身代谢功能障碍之间的差距。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-12-01 Epub Date: 2024-12-17 DOI: 10.1080/13543784.2024.2441865

Eda Kaya, Yusuf Yilmaz, Naim Alkhouri

{"title":"Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction.","authors":"Eda Kaya, Yusuf Yilmaz, Naim Alkhouri","doi":"10.1080/13543784.2024.2441865","DOIUrl":"10.1080/13543784.2024.2441865","url":null,"abstract":"Introduction: Glucagon-like peptide-1 receptor (GLP-1 R) agonists have demonstrated remarkable effectiveness in the treatment of obesity and type 2 diabetes. Although these agents provide beneficial effects for metabolic dysfunction-associated steatohepatitis (MASH) through their glucose-lowering and weight-reducing properties, their efficacy in promoting fibrosis regression remains unproven. Survodutide, an investigational dual agonist that simultaneously targets both the glucagon receptor (GCGR) and GLP-1 R, has emerged as a promising therapeutic candidate for the comprehensive management of obesity and MASH. By engaging these two critical receptors, this drug has the potential to offer a broad spectrum of metabolic benefits, addressing multiple pathogenic mechanisms underlying these interrelated disorders.Areas covered: This review examines the pharmacological profile, clinical efficacy, and safety data of survodutide derived from phase 1 and 2 clinical trials.Expert opinion: Survodutide's dual agonism of the GCGR and GLP-1 R may surpass the efficacy of selective GLP-1 R agonists, demonstrating significant potential in resolving MASH and promoting fibrosis regression. The drug is generally well tolerated, with primarily manageable gastrointestinal adverse effects. As survodutide progresses through phase 3 clinical development, its potential to provide a more effective and holistic approach to treating MASH and its comorbidities may significantly improve patient outcomes and quality of life.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1167-1176"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812550","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

Hepatic encephalopathy: experimental drugs in development and therapeutic potential. 肝性脑病：开发中的实验药物和治疗潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-12-01 Epub Date: 2024-11-26 DOI: 10.1080/13543784.2024.2434053

Antonio Gil-Gómez, Rocío Muñoz-Hernández, Filomeno Martínez, Fernando Jiménez, Manuel Romero-Gómez

{"title":"Hepatic encephalopathy: experimental drugs in development and therapeutic potential.","authors":"Antonio Gil-Gómez, Rocío Muñoz-Hernández, Filomeno Martínez, Fernando Jiménez, Manuel Romero-Gómez","doi":"10.1080/13543784.2024.2434053","DOIUrl":"10.1080/13543784.2024.2434053","url":null,"abstract":"Introduction: Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.Areas covered: Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases. Advancements in understanding HE reveal a growing need for personalized treatments. Novel approaches targeting immune modulation and neuroinflammation are under investigation, though clinical translation is slow. Nutritional interventions and fecal microbiota transplantation show potential but lack robust evidence. Innovative therapies like gene and cell therapies, as well as extracellular vesicles from mesenchymal stem cells, present promising avenues for liver disease treatment, potentially benefiting HE.Expert opinion: A key challenge in HE research is the design of randomized clinical trials, which often suffer from small sample sizes, heterogeneity in patient population, and inconsistent blinding. Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1219-1230"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715915","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