Expert opinion on investigational drugs最新文献

{"title":"Unlocking the mechanisms underlying the activity of pembrolizumab plus enfortumab vedotin in patients with urothelial carcinoma.","authors":"Matteo Santoni, Alessandro Rizzo, Francesco Massari","doi":"10.1080/13543784.2025.2473695","DOIUrl":"10.1080/13543784.2025.2473695","url":null,"abstract":"<p><strong>Introduction: </strong>Urothelial carcinoma (UC) is frequently associated with a poor prognosis in patients with advanced disease. A strong biological rationale supports the investigation of combining antibody-drug conjugates (ADCs) with immunotherapy to overcome the occurrence of resistance and improve patient outcomes.</p><p><strong>Areas covered: </strong>In this review, we illustrate the mechanisms of action of pembrolizumab and enfortumab vedotin (EV) and the immune and biological rationales underlying their synergy in mUC patients.</p><p><strong>Expert opinion: </strong>The results of the combination of EV and pembrolizumab represent a ray of light in the therapeutic scenario of mUC patients. A deeper understanding of the mechanisms underlying the synergistic effects of these agents will be crucial to reduce drug-resistance and further improve the outcome of mUC patients.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"259-265"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515091","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}

{"title":"The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma.","authors":"Harry Hambleton, Chan Y Cheah","doi":"10.1080/13543784.2025.2500290","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500290","url":null,"abstract":"<p><strong>Introduction: </strong>Follicular lymphoma (FL) is the most common indolent lymphoma. Patients with advanced-stage FL typically respond to therapy, then follow a relapsing/remitting course, with shorter progression-free survival with each subsequent line of therapy. Whilst existing CD19-directed therapies such as CAR T-cell therapy have shown promising efficacy in the management of relapsed/refractory FL, immune-mediated adverse events, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), are well described. AZD0486 is a fully human bispecific (CD19×CD3) T-cell engager (TCE) that induces T cell-mediated cytotoxicity but with low-affinity binding of CD3, resulting in a reduction in cytokine release.</p><p><strong>Areas covered: </strong>In this review, we describe the key preclinical data for AZD0486 and evaluate in detail the available clinical data from the ongoing phase 1 first-in-human study, including safety, efficacy, pharmacokinetics, and future development plans.</p><p><strong>Expert opinion: </strong>Bispecific TCEs are among the most promising novel therapies in use for the management of relapsed/refractory B-cell lymphomas. AZD0486 results in high complete response rates with low incidence of high-grade immune-mediated toxicity compared to alternative TCE therapies. Importantly, it remains active in patients with lymphomas that have lost CD20 expression, an important mechanism of treatment failure following CD20 targeting TCEs.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"245-252"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005268","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}

{"title":"Endothelin receptor antagonists for diabetic kidney disease: back to the future?","authors":"Panagiota Anyfanti, Marieta Theodorakopoulou, Fotini Iatridi, Pantelis Sarafidis","doi":"10.1080/13543784.2025.2500294","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500294","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease worldwide. Endothelin-1 (ET-1) is a potent vasoconstrictor secreted by vascular endothelial cells, actively involved in the pathophysiology of numerous cardiovascular diseases. Based on the differential downstream effects of ET-1 binding to its two distinct types of receptors (ET_A/ET_B) within the kidney, selective ET_A receptor blockade has been long proposed as a promising treatment modality for DKD.</p><p><strong>Areas covered: </strong>This review aims to examine the available evidence base for the use of ERAs in the treatment of DKD, by critically reappraising available landmark trials and discussing their possible position in the context of current treatment of this disease.</p><p><strong>Expert opinion: </strong>Despite early enthusiasm and widespread expectations, endothelin receptor antagonists (ERAs) faded into obscurity following the release of the first randomized controlled trials (RCTs). More recent RCTs using different compounds have re-introduced ERAs as a promising treatment in the growing pharmaceutical armamentarium of DKD. While the future of DKD management will be based on a more personalized approach, new, robust evidence from appropriately designed RCTs is eagerly anticipated to clearly define the role of ERAs in DKD.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"317-327"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976790","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}

{"title":"Chronic lymphocytic leukemia: what clinical progress have we seen in the last five years?","authors":"Elżbieta Iskierka-Jażdżewska, Bartosz Puła, Krzysztof Jamroziak, Tadeusz Robak","doi":"10.1080/13543784.2025.2500288","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500288","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. Although treatment has shifted from immunochemotherapy to novel targeted drugs over the last 10 years, novel therapies remain under investigation, particularly in relapsed and refractory patients.</p><p><strong>Areas covered: </strong>This review describes the use of approved targeted drugs and novel therapies in treatment-naïve and relapsed or refractory CLL. Particular attention is paid to the management of double-refractory patients, and the discovery of novel drugs in the last five years.</p><p><strong>Expert opinion: </strong>Targeted drugs are effective and well-tolerated in the treatment of CLL. In the last five years, several novel agents have been investigated in preclinical studies and clinical trials, including combinations of approved drugs, novel BTK and BCL2 inhibitors, BTK degraders, bispecific antibodies and CAR-T cells. It is anticipated that some should be approved in the near future.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"267-285"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994351","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}

{"title":"Pharmacokinetic equivalence and comparative safety, tolerability, and immunogenicity of Biocon's ustekinumab (Bmab-1200) with EU-approved and US-licensed reference ustekinumab in healthy subjects: results from the Study to Test pharmacokinetic BioEquivalence of BiosimiLar ustekinumab to SteLARa (STELLAR-1).","authors":"Jonathan Ackroyd, Sarika S Deodhar, Subramanian Loganathan, Gursharan Singh, Ashwani Marwah, Kuldeep Kumar, Jayanti Panda, Sandeep Nilkanth Athalye","doi":"10.1080/13543784.2025.2500334","DOIUrl":"10.1080/13543784.2025.2500334","url":null,"abstract":"<p><strong>Background: </strong>This study assessed the pharmacokinetics (PK) equivalence, safety, tolerability, and immunogenicity of Bmab-1200 versus the reference product ustekinumab (EU-approved and US-licensed Stelara).</p><p><strong>Research design & methods: </strong>This 20-week, randomized, double-blind, three-arm, parallel-design, Phase-1 study enrolled healthy male and female subjects (<i>n</i> = 258; 18-55 years). A single, 45-mg subcutaneous injection of Bmab-1200, EU-approved Stelara, or US-licensed Stelara was administered in a 1:1:1 ratio. Subject stratification was performed by ethnicity, body weight range, and gender. Primary PK endpoints included AUC_0-inf and C_max. Secondary endpoints included additional PK parameters, immunogenicity, and safety and tolerability.</p><p><strong>Results: </strong>All three pairwise comparisons of Bmab-1200 versus US-Stelara, Bmab-1200 versus EU-Stelara, and US-Stelara versus EU-Stelara were equivalent for AUC_0-inf (90% confidence intervals [CIs] of the geometric least squares mean [GLSM] ratio: 0.9975-1.1657, 0.9959-1.1685, and 0.9223-1.0921, respectively) and C_max (90% CIs of the GLSM ratio: 0.9478-1.0732, 0.9136-1.0376, and 0.9012-1.0267, respectively). All secondary analyses supported the primary results.</p><p><strong>Conclusion: </strong>Three-way PK equivalence between Bmab-1200, US-Stelara, and EU-Stelara was demonstrated. A single, 45-mg dose of Bmab-1200 was safe and well tolerated, and, overall, the number of AEs was similar among the groups. Diversity limited to White and Japanese groups did not impact the study results.</p><p><strong>Clinical trial registration: </strong>This study was registered with www.isrctn.com; identifier: ISRCTN11424009.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"349-357"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958615","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}

{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-2010, a novel anti-MASP-2 antibody, in healthy volunteers: a randomized, double-blind, placebo-controlled phase 1 study.","authors":"Pingping Lin, Chenjing Wang, Xiaotong Hu, Lin Fang, Hongda Lin, Feifei Sun, Rong Huang, Rongxin Ban, Sheng Feng, Zhenyan Gao, Kai Shen, Yu Cao","doi":"10.1080/13543784.2025.2500291","DOIUrl":"10.1080/13543784.2025.2500291","url":null,"abstract":"<p><strong>Background: </strong>This first-in-human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-2010, a novel humanized IgG4 monoclonal antibody targeting mannan-binding lectin serine protease-2, in healthy adults.</p><p><strong>Research design and methods: </strong>In this randomized, double-blind, phase 1 study, eligible participants were randomly assigned to single ascending doses of SHR-2010 or placebo (32 via intravenous drip: 6:2; 0.3, 1.5, 4.0, and 8.0 mg/kg; 29 via subcutaneous injection: 8:2; 4.0, 8.0, and 12.0 mg/kg). The primary endpoints were safety and tolerability.</p><p><strong>Results: </strong>SHR-2010 was well tolerated. Treatment-related adverse events (TRAEs) were similar in SHR-2010 groups (55.3% [26/47]) and placebo groups (78.6% [11/14]). No deaths or severe TRAEs were reported. In the intravenous dose groups, the C_max increased proportionally with the dose, while the AUC increased slightly more than the dose increment. In the subcutaneous injection groups, C_max and AUC demonstrated a linear relationship with dose. SHR-2010 demonstrated a notable inhibitory effect on lectin pathway, with the mean maximum inhibition rates exceeding 80.0% across the tested doses, compared to 6.7% with placebo.</p><p><strong>Conclusions: </strong>SHR-2010 was safe and well tolerated after a single dose and exhibited robust blockade of the lectin pathway, supporting further development.</p><p><strong>Trial registration: </strong>The trial is registered at ClinicalTrials.gov (NCT05398510).</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"339-348"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985640","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}

{"title":"Neuropathic pain management: a focused review of current treatments and novel data from main ongoing clinical trials.","authors":"Nikola Andrejic, Ivo Božovic, Hadi Moradi, Rojin Tataei, Nebojsa Nick Knezevic","doi":"10.1080/13543784.2025.2473692","DOIUrl":"10.1080/13543784.2025.2473692","url":null,"abstract":"<p><strong>Introduction: </strong>Neuropathic pain (NP) remains a significant challenge in clinical practice, requiring a sophisticated pharmacotherapeutic strategy for effective symptom management. This review provides a comprehensive analysis of the current pharmacological treatments for NP, focusing on their efficacy, mechanism of action, and therapeutic potential. Additionally, it evaluates ongoing clinical trials investigating novel drugs and therapeutic approaches, highlighting emerging trends and future directions in NP management.</p><p><strong>Areas covered: </strong>This review examines first- to third-line therapeutic modalities for NP, critically analyzing their efficacy, safety profiles, and clinical applications. It also includes an overview of ongoing clinical trials exploring innovative pharmacological therapies. A thorough literature review was conducted using the MEDLINE database without temporal limitations, offering a detailed assessment of established and emerging treatments.</p><p><strong>Expert opinion: </strong>While current pharmacological options offer significant symptom relief, their overall effectiveness in managing NP remains limited, highlighting the need for further therapeutic advancements. Staying informed about emerging therapies and clinical trials is vital to enhancing patient care and quality of life. The future of NP management lies in optimizing individualized treatment strategies, refining therapeutic approaches, and fostering interdisciplinary collaboration. Close monitoring of outcomes and continued research are essential for advancing understanding and improving the precision of NP therapies.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"287-299"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523028","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}

{"title":"Assessing the clinical progress of the bispecific nanobody sonelokimab.","authors":"Sunil Dogra, Sukhdeep Singh","doi":"10.1080/13543784.2025.2500292","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500292","url":null,"abstract":"<p><strong>Introduction: </strong>Sonelokimab, a bispecific nanobody targeting interleukins (IL)-17A and IL-17F, has emerged as a novel therapeutic candidate for chronic inflammatory diseases, such as psoriasis, hidradenitis suppurativa (HS), and psoriatic arthritis. Its innovative design offers improved tissue penetration, rapid clearance, and reduced immunogenicity, addressing limitations of current monoclonal antibody therapies.</p><p><strong>Areas covered: </strong>This review evaluates the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile of sonelokimab, drawing from data obtained in phase 1 and 2 trials. Key findings highlight its superior performance in disease-specific indices such as the Psoriasis Area and Severity Index (PASI) and Hidradenitis Suppurativa Clinical Response (HiSCR). A favorable safety profile with common adverse effects like nasopharyngitis, pruritus, headache have been reported.</p><p><strong>Expert opinion: </strong>Sonelokimab's dual inhibition of IL-17A and IL-17F provides enhanced efficacy over single-target therapies. Its nanobody-based structure enables deeper tissue penetration and better disease control. Further phase 3 trials and head-to-head studies are crucial to establish its long-term efficacy and safety, potentially positioning it as a leading therapeutic option.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"253-258"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979199","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}

{"title":"Clinical development of BPS804 for osteogenesis imperfecta: from failure to fruition?","authors":"Roland Chapurlat","doi":"10.1080/13543784.2025.2472242","DOIUrl":"10.1080/13543784.2025.2472242","url":null,"abstract":"","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"105-107"},"PeriodicalIF":4.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482592","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}

{"title":"Ongoing phase 2 agents for multiple sclerosis: could we break the phase 3 trial deadlock?","authors":"Silvia Susin-Calle, Jose Enrique Martinez-Rodriguez, Elvira Munteis, Pablo Villoslada","doi":"10.1080/13543784.2025.2472240","DOIUrl":"10.1080/13543784.2025.2472240","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. While disease-modifying therapies have significantly improved the management of relapsing MS, progressive MS remains a major clinical challenge.</p><p><strong>Areas covered: </strong>This review provides a general overview of recent and ongoing phase 2 clinical trials investigating treatments for MS, summarizing emerging results when available. The trials are categorized based on the desired therapeutic effect: immunomodulatory treatments, neuroprotection, and remyelination. A comprehensive literature search was conducted using databases such as PubMed and ClinicalTrials.gov to identify relevant studies, with a focus on promising therapies that address both inflammatory and neurodegenerative processes in MS.</p><p><strong>Expert opinion: </strong>Despite promising results from phase 2 trials, many phase 3 trials fail to demonstrate significant efficacy. This discrepancy is partly due to limitations in biomarkers, which often lack disease specificity and fail to predict long-term outcomes. Additionally, smaller, narrowly focused phase 2 trials may overestimate efficacy, leading to challenges when transitioning to larger, more inclusive phase 3 trials. Recruitment of patients with less aggressive disease further complicates phase 3 success. Addressing these challenges requires the refinement of biomarkers, adoption of unified definitions for outcomes like progression independent of relapse activity (PIRA), and trial designs that better capture the complexity of MS progression.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"217-229"},"PeriodicalIF":4.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499803","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}