Expert opinion on investigational drugs最新文献

Zovegalisib for PIK3CA-driven vascular and lymphatic malformations: a drug evaluation. Zovegalisib治疗pik3ca驱动的血管和淋巴畸形：一种药物评估。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-10-17 DOI: 10.1080/13543784.2026.2750463

Emmanuel Seront, An Van Damme, Julien Coulie, Miikka Vikkula, Laurence M Boon

{"title":"Zovegalisib for PIK3CA-driven vascular and lymphatic malformations: a drug evaluation.","authors":"Emmanuel Seront, An Van Damme, Julien Coulie, Miikka Vikkula, Laurence M Boon","doi":"10.1080/13543784.2026.2750463","DOIUrl":"10.1080/13543784.2026.2750463","url":null,"abstract":"Introduction: PIK3CA-driven overgrowth and vascular malformations are mosaic developmental disorders in which chronic pathway inhibition may be required from childhood into adulthood. Alpelisib established PI3Kα as a clinically actionable target, but inhibition of wild-type PI3Kα can produce on-target toxicities, principally hyperglycemia, diarrhea and stomatitis, that are relevant to long-term therapy. Zovegalisib (RLY-2608) is an oral allosteric, pan-mutant-selective PI3Kα inhibitor designed to preferentially inhibit mutant over wild-type PI3Kα.Areas covered: This Drug Evaluation reviews PIK3CA biology, the current systemic-treatment landscape, zovegalisib pharmacology, and the preliminary Phase 2 ReInspire data. PubMed/MEDLINE, ClinicalTrials.gov, regulatory sources, and publicly available conference materials and company disclosures were reviewed through 20 August 2026.Expert opinion: At the formal 15 April 2026 cutoff, early ReInspire results showed a 60% week-12 volumetric response rate in 20 evaluable adults/adolescents; one unconfirmed response reported after the cutoff in a sponsor press release increased the descriptive rate to 65%. Activity after prior sirolimus and/or alpelisib and encouraging short-term tolerability support further development. Mutant selectivity could be especially valuable in chronic nonmalignant disease, but superiority over alpelisib is unproven.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-8"},"PeriodicalIF":4.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the proteasome in Leishmania donovani: developments from preclinical to Phase I and ii trials. 针对多诺瓦利什曼原虫的蛋白酶体：从临床前到I期和ii期试验的进展。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-10-14 DOI: 10.1080/13543784.2026.2750461

Shyam Sundar, Sarita Singh, Priya Maurya, Vishal Kumar Singh, Rajiv Kumar

{"title":"Targeting the proteasome in Leishmania donovani: developments from preclinical to Phase I and ii trials.","authors":"Shyam Sundar, Sarita Singh, Priya Maurya, Vishal Kumar Singh, Rajiv Kumar","doi":"10.1080/13543784.2026.2750461","DOIUrl":"https://doi.org/10.1080/13543784.2026.2750461","url":null,"abstract":"Introduction: Visceral leishmaniasis (VL), a neglected tropical disease caused by Leishmania donovani and L. infantum, which affects poor areas of South Asia, East Africa, and Brazil, and is fatal if left untreated. Current treatments, including liposomal amphotericin B, miltefosine, paromomycin, and pentavalent antimonials, are limited by emerging resistance, high cost, cold storage, need for parenteral administration. These drawbacks of the currently available therapy entail the development of a safe, short, and oral therapy for VL treatment.Area covered: This review summarizes current knowledge of the Leishmania 20S proteasome as a therapeutic target, as it maintains protein homeostasis and exhibits structural variances from the human proteasome that allow selective, parasite-specific inhibition. It covers the preclinical story of GSK3494245 to the story of proteasome inhibitors, especially LXE408, which has progressed from Phase I evaluation to Phase II clinical trials in India and Ethiopia. Collectively, these results place proteasome inhibition as a promising clinical approach that may revolutionize the VL treatment.Expert opinion: Proteasome inhibitors provide strong antiparasitic activity, high selectivity and a potential for oral treatment. If the ongoing clinical trials show safety, efficacy and durable cure rates, proteasome-targeting drugs will revolutionize VL therapy and be a model for drug development against other neglected tropical diseases.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180344","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

Dual antigen targeting in extramedullary multiple myeloma. Talquetamab + Teclistamab双抗原靶向：髓外多发性骨髓瘤的新视野？

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-10-12 DOI: 10.1080/13543784.2026.2746598

Binish Javed, Shaji Kumar

引用次数: 0

Evaluating early systemic therapies in the neoadjuvant setting for the treatment of urological cancers. 评估泌尿系统肿瘤新辅助治疗的早期全身疗法。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-10-12 DOI: 10.1080/13543784.2026.2748359

Panagiotis Velissarios Stamatakos, Charalampos Fragkoulis, Nikolaos Kontolatis, Konstantinos Gklinos, Christoforos Kourouniotis, Athanasios Dellis

{"title":"Evaluating early systemic therapies in the neoadjuvant setting for the treatment of urological cancers.","authors":"Panagiotis Velissarios Stamatakos, Charalampos Fragkoulis, Nikolaos Kontolatis, Konstantinos Gklinos, Christoforos Kourouniotis, Athanasios Dellis","doi":"10.1080/13543784.2026.2748359","DOIUrl":"https://doi.org/10.1080/13543784.2026.2748359","url":null,"abstract":"Introduction: Neoadjuvant systemic therapy represents an evolving cornerstone in the multidisciplinary management of urological malignancies. While cisplatin-based neoadjuvant chemotherapy historically represented the sole standard of care for muscle-invasive bladder cancer, novel perioperative regimens - combining preoperative induction with adjuvant maintenance - have established chemotherapy as only a standard of care alongside emerging antibody-drug conjugate and immunotherapy combinations. In renal cell carcinoma and prostate cancer, preoperative approaches remain largely investigational.Areas covered: A structured search of PubMed/MEDLINE, Embase, and ClinicalTrials.gov was conducted up to August 2026. This review critically appraises prospective Phase I and II investigational trials evaluating novel systemic therapies across renal cell carcinoma, upper tract urothelial carcinoma, muscle-invasive bladder cancer, and prostate cancer, contextualizing pivotal Phase III benchmarks.Expert opinion: Neoadjuvant and perioperative paradigms are shifting toward personalized, biomarker-driven strategies. Key challenges include determining the independent necessity of postoperative maintenance in pathological complete responders, establishing validated surrogate endpoints in renal cell carcinoma and prostate cancer, and overcoming significant socioeconomic and geographic access disparities. Incorporating circulating tumor DNA kinetics and predictive biomarkers will be pivotal for optimizing patient selection and guiding response-adaptive therapy.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164899","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, pharmacodynamics and target-mediated drug disposition modeling of TST002, a sclerostin antibody, in men and postmenopausal women with low bone mineral density. TST002（一种硬化蛋白抗体）在低骨密度男性和绝经后女性中的安全性、药代动力学、药效学和靶向介导的药物处置模型

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-22 DOI: 10.1080/13543784.2026.2736007

Sufeng Zhou, Xiufen Zhu, Yuchen Sheng, Lu Wang, Feng Shao, Hua Lin

{"title":"Safety, pharmacokinetics, pharmacodynamics and target-mediated drug disposition modeling of TST002, a sclerostin antibody, in men and postmenopausal women with low bone mineral density.","authors":"Sufeng Zhou, Xiufen Zhu, Yuchen Sheng, Lu Wang, Feng Shao, Hua Lin","doi":"10.1080/13543784.2026.2736007","DOIUrl":"10.1080/13543784.2026.2736007","url":null,"abstract":"Background: TST002 is a humanized IgG4 monoclonal antibody targeting sclerostin for osteoporosis treatment. This first-in-human study investigated its safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) after intravenous infusion in Chinese men and postmenopausal women with low bone mineral density (BMD).Research design and methods: In a randomized, double-blind, placebo-controlled, dose-escalation trial, 32 subjects were assigned to four dose cohorts (3:1 ratio to receive single TST002 doses of 200, 400, 800, or 1200 mg or placebo) with 85 days of follow-up. PK, PD, safety, and immunogenicity were assessed. An exploratory population PK-PD model incorporating target-mediated drug disposition (TMDD) was developed.Results: Among TST002 recipients (n = 24), most treatment-related adverse events were grade 1 in severity. Nonlinear PK was observed, with greater-than-dose-proportional exposure and a mean half-life of 4.38-8.06 days. Increases in serum sclerostin and lumbar spine BMD, and decreases in β-CTX were observed. An exploratory population TMDD-PD model was developed to describe the observed time courses of TST002, sclerostin, and β-CTX within the present phase I dataset.Conclusions: TST002 was well tolerated and showed preliminary PD activity. Exploratory TMDD-based PK/PD modeling provided preliminary insights into exposure-response relationships, limited by the sample size, single-dose design, and unavailable bone formation marker assessment.Clinical trial registration: This study was registered at Clinicaltrials.gov (NCT05391776).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976154","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

Emerging therapeutic strategies and clinical development of investigational agents for conventional chondrosarcoma. 传统软骨肉瘤的新兴治疗策略和研究药物的临床发展。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-20 DOI: 10.1080/13543784.2026.2734584

Carlos Torrado, Anthony P Conley

{"title":"Emerging therapeutic strategies and clinical development of investigational agents for conventional chondrosarcoma.","authors":"Carlos Torrado, Anthony P Conley","doi":"10.1080/13543784.2026.2734584","DOIUrl":"10.1080/13543784.2026.2734584","url":null,"abstract":"Introduction: Conventional chondrosarcoma (cCS) is a malignant bone tumor with intrinsic resistance to cytotoxic therapy. Advances in genomic profiling have revealed recurrent alterations that are redefining the therapeutic landscape for these tumors.Areas covered: Literature searches of PubMed and ClinicalTrials.gov for the terms conventional chondrosarcoma, systemic therapy, targeted therapy, immunotherapy, chemotherapy, molecular targets, and clinical trial through June 2026 were performed. Clinical and translational developments regarding treatment of cCS were summarized, emphasizing the following emerging targeted and immunotherapeutic agents: isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors, DR5 agonists, methylthioadenosine phosphorylase (MTAP)-deficient PRMT5 inhibitors, TP53 reactivators, histone deacetylase and BCL-2 modulators, immunotherapy approaches, multi-targeted tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates.Expert opinion: Multi-targeted TKIs remain the most commonly used systemic therapies for advanced cCS; however, recent advances in DR5 agonism and IDH1 inhibition provide proof of concept that biologically informed therapeutic strategies can achieve meaningful clinical benefit. Continued progress will require comprehensive molecular profiling, rational combination strategies, and innovative clinical trial designs to accelerate drug development in this rare malignancy.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988313","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

Innovative therapies under clinical development for ALS treatment. Part 2: biologics and natural products. ALS治疗的创新疗法正在临床开发中。第2部分：生物制剂和天然产物。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-12 DOI: 10.1080/13543784.2026.2729512

Chi-Chen Sarah Huang, Cecilia Sanchez-Santos, Loreto Martinez-Gonzalez, Carmen Gil, Ana Martinez

{"title":"Innovative therapies under clinical development for ALS treatment. Part 2: biologics and natural products.","authors":"Chi-Chen Sarah Huang, Cecilia Sanchez-Santos, Loreto Martinez-Gonzalez, Carmen Gil, Ana Martinez","doi":"10.1080/13543784.2026.2729512","DOIUrl":"10.1080/13543784.2026.2729512","url":null,"abstract":"Introduction: The clinical trial landscape for Amyotrophic Lateral Sclerosis (ALS) is rapidly expanding despite ongoing translational challenges. Following our 2022 analysis and as a continuation of Part 1, which focused on small molecules, this review provides a structured overview of biologics and natural products in the ALS clinical pipeline. Particular emphasis is placed on candidates that entered, advanced through, or completed clinical evaluation between 2022 and the end of 2025.Areas covered: Clinical trials for ALS registered in the United States (ClinicalTrials.gov) and the European Union (EU Clinical Trials Register/CTIS) were systematically reviewed and are summarized in this report.Expert opinion: Modern biotechnology, ethnopharmacology, and classical pharmacology are increasingly converging in ALS therapeutic development, making this one of the most active areas of neurodegenerative disease research. Nevertheless, major challenges remain, including central nervous system (CNS) penetration, long-term safety, interpatient variability, limited clinical evidence, and the need for reliable biomarkers. Emerging technologies, such as big data analytics and artificial intelligence, may help accelerate and optimize therapeutic development, as well as improve patient recruitment and stratification.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-19"},"PeriodicalIF":4.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929412","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

Up and coming early phase CAR T-cell therapy for treating relapsed or refractory large B-cell lymphoma. 即将到来的早期CAR - t细胞疗法治疗复发或难治性大b细胞淋巴瘤。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-01 Epub Date: 2026-09-02 DOI: 10.1080/13543784.2026.2727498

Dasom Lee, Masooma Rana, Arvin Eslami, Saurabh Dahiya

引用次数: 0

Receptor interacting protein kinase 1 as a potential therapeutic target in inflammatory bowel disease: biological rationale and emerging clinical evidence. 受体相互作用蛋白激酶1作为炎症性肠病的潜在治疗靶点：生物学原理和新出现的临床证据

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-01 Epub Date: 2026-08-13 DOI: 10.1080/13543784.2026.2717160

Sailish Honap, Axel Dignass, Vipul Jairath, Fernando Magro, Silvio Danese, Laurent Peyrin-Biroulet

{"title":"Receptor interacting protein kinase 1 as a potential therapeutic target in inflammatory bowel disease: biological rationale and emerging clinical evidence.","authors":"Sailish Honap, Axel Dignass, Vipul Jairath, Fernando Magro, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1080/13543784.2026.2717160","DOIUrl":"10.1080/13543784.2026.2717160","url":null,"abstract":"Introduction: Inflammatory bowel disease (IBD) remains a major cause of morbidity, with many patients failing to achieve sustained remission and mucosal healing. Receptor-interacting protein kinase 1 (RIPK1) is a potential therapeutic target that links tumor necrosis factor receptor signaling to inflammation, apoptosis, and necroptosis, processes relevant to epithelial injury and barrier dysfunction in IBD.Areas covered: This narrative review summarizes the biological rationale and translational and clinical evidence for targeting RIPK1 in IBD. MEDLINE was searched from database inception to March 2026 to identify relevant articles. Preclinical studies across cell systems, human tissue, and murine colitis models, suggest that RIPK1 kinase activity contributes to inflammatory signaling, epithelial injury, and necroptosis, while selective inhibition attenuates these processes and ameliorates experimental colitis. However, RIPK1 also has kinase-independent scaffolding functions important for epithelial homeostasis, highlighting the complexity of therapeutic targeting. GSK2982772 did not demonstrate convincing efficacy, whereas clinical efficacy data for newer RIPK1 inhibitors, including ABBV-668 and eclitasertib, have not yet been reported.Expert opinion: RIPK1 remains a compelling but clinically unvalidated target in IBD. Future progress will depend on improved patient selection, confirmation of mucosal target engagement, and better recognition of patients in which RIPK1 signaling is a key driver.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"675-684"},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720827","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

Varespladib for snakebite envenoming: insights from therapeutic development and clinical trials. Varespladib为蛇咬伤的环境。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1080/13543784.2026.2727499

Madison R McGann, Timothy F Platts-Mills, Charles J Gerardo

{"title":"Varespladib for snakebite envenoming: insights from therapeutic development and clinical trials.","authors":"Madison R McGann, Timothy F Platts-Mills, Charles J Gerardo","doi":"10.1080/13543784.2026.2727499","DOIUrl":"10.1080/13543784.2026.2727499","url":null,"abstract":"Introduction: Snakebite envenoming (SBE) causes significant worldwide morbidity and mortality. Patients often face barriers to and delays in accessing antivenom, an effective yet time-sensitive treatment. Finding alternative drugs that could be administered early has the potential to improve SBE outcomes. Phospholipases A2 (PLA2s) are a group of toxins that are common in snake venoms and responsible for many life- and limb-threatening toxicities. Varespladib is an investigational small molecule that broadly inhibits PLA2s and can be given orally or intravenously.Areas covered: Preclinical and clinical evidence for the use of varespladib in SBE. We review in vitro studies, animal studies, human safety and tolerability data and the two randomized control trials of varespladib for treatment of SBE.Expert opinion: There is strong preclinical evidence that varespladib can prevent and treat severe toxicity in animal models of SBE. In two clinical studies in patients with SBE, varespladib has been safe and well tolerated. Clinical evidence from these studies supports further evaluation of varespladib as an in-hospital treatment administered, with encouraging signals from Agkistrodon contortrix (copperhead), Micrurus fulvius (eastern coral snake), and Bungarus spp (krait). Additional studies may provide insight into the benefit of varespladib as a time-of-bite treatment in specific regions.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"657-666"},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879391","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